系统性红斑狼疮OAZ基因通路的研究
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摘要
目的：探讨系统性红斑狼疮(SLE)患者OAZ通路相关基因的功能。
方法：实验一：收集SLE患者和正常对照骨髓前体细胞(各5例),提取RNA,逆转录为cDNA,加入相应的引物、SYBR Green I在ABI Prism 7500型高通量荧光定量仪上进行实时荧光定量PCR,采用看家基因酸性核糖体磷蛋白大亚基(RPLPO)进行标化,观察OAZ、Id3、BMP4、BMP6、Smad6、EHZF、LY6E基因的表达量与SLE疾病活动相关指标关系。同时收集30例SLE患者和20例正常人外周血细胞,对上述结果进行验证。
实验二：采集并分离SLE患者外周血单个核细胞,分为实验组、阳性对照组、阴性对照组和空白对照组进行细胞培养。实验组和阳性对照组分别用OAZ和GAPDH小干扰RNA(siRNA)在体外对培养细胞进行干扰,阴性对照组采用无关RNA序列,空白对照组为培养基对照。72小时后分离细胞和上清液,从细胞中提取RNA,逆转录为cDNA,用实时荧光定量PCR分析不同分组OAZ信号通路相关基因OAZ、Id1、Id2、Id3、Id4mRNA表达水平的变化。ELISA法测定上清液中IFN-γ、IL4、IL10、IL12、IL21、CCL2、ANA浓度,并分析这些因子分泌水平与OAZ基因表达的相关性。
实验三：从骨髓或脐带血中分离培养间充质干细胞(MSC)移植治疗10例SLE患者,采集并分离移植前、移植后1周、4周患者外周血有核细胞,从细胞中提取RNA,逆转录为cDNA,用实时荧光定量PCR技术分析不同分组OAZ信号通路相关基因OAZ、Id1、Id2、Id3 mRNA表达水平的变化。ELISA法测定移植前后患者血清中IL10、IL12、IL21、CCL2、ANA浓度,并分析这些因子分泌水平与OAZ基因表达的相关性。
结果：实验一：SLE患者骨髓前体细胞OAZ、Id3基因的mRNA表达水平(△Ct分别为10.6±0.5、5.8±3.2)较正常对照组(△Ct分别为16.5±0.9、10.4±2.6)显著增高,且表达水平高于外周血细胞；BMP6、BMP4基因表达水平虽较正常对照有高表达趋势,但差异无统计意义。SLE患者外周血细胞OAZ、Id3、BMP4、BMP6mRNA基因表达(△Ct分别为14.1±2.7、7.5±1.8、7.6±3.3、5.2±2.2)均显著高于正常(△Ct分别为16.1±2.2、9.5±1.7、9.7±0.3、6.4±1.2)。骨髓前体细胞OAZ、BMP6、BMP4、Id3的表达水平ACt值与SLEDAI积分、肾脏损伤指数、抗双链DNA (dsDNA)抗体、RNA相关抗体水平呈负相关；与补体C3呈正相关。
实验二：实验组OAZ、Id1、Id2、Id3基因的mRNA表达水平(△Ct分别为12.5±1.4、8.9±1.5、4.3±0.8、8.0±1.1)较阴性对照组(△Ct分别为10.2±1.1、6.5±1.2、2.4±1.3、6.2±1.2)显著降低(P<0.05)；Id4表达水平虽较阴性对照组有低表达趋势,但差异无统计学意义。实验组IFN-γ、IL10、IL12、IL21、ANA的水平明显低于阴性对照组；而CCL2高于阴性对照组(P<0.05)。实验组与阴性对照组OAZ mRNA表达水平△△Ct值与ANA的OD比值、IL21浓度比值呈负相关；与Th1/Th2、CCL2比值呈正相关。
实验三：移植后1周、4周OAZ、Id1、Id3基因的mRNA表达水平[ACt(1周)分别为12.4±1.1、9.7±1.9、9.7±1.9、2.1±1.0；△Ct(4周)分别为13.3±1.2、10.4±1.5、10.8±1.2、2.1±1.2]较移植前(△Ct分别为11.0±0.9、7.4±2.1、7.8±2.1、0.1±1.5)均显著降低(P<0.05)；Id2表达水平虽较移植前有低表达趋势,但差异无统计学意义。移植4周后IL10、IL21、ANA的水平明显低于移植前,IL12／IL10、CCL2高于移植前(P<0.05),但移植后1周的水平较移植前没有差异。移植前与移植后4周OAZ mRNA表达水平变化与ANA的OD值和IL21浓度比值呈负相关；与IL12/IL10、CCL2比值呈正相关。
结论：一：OAZ通路相关基因在SLE中异常表达,与疾病发生相关。
二：OAZ基因沉默可有效降低狼疮外周血单个核细胞中OAZ信号通路相关基因表达,同时减低多种细胞因子及抗核抗体水平,推测OAZ可能通过Id基因影响细胞因子的水平并导致ANA异常表达。
三：同种异体MSC移植治疗SLE可降低患者外周血中OAZ信号通路相关基因表达,同时减低多种细胞因子及抗核抗体水平,推测OAZ信号通路是MSC移植治疗SLE有效机制之一。
Objective To investigate the function of genes involved in OAZ signaling pathway in the patients with systemic lupus erythematosus (SLE)
Methods Part one:The expression levels of OAZ, BMP6, BMP4, Id3, Smad6, EHZF、LY6E genes were valuated in bone marrow progenitor cells of 5 SLE patients and 5 normal subjects and replicated in peripheral blood cells of 30 SLE patients and 20 normal individuals by real-time quantitative PCR technique. Relationships of the expression levels of OAZ, BMP6, BMP4, Id3、LY6E mRNA with disease activity and other clinical index were analyzed.
Part two:Peripheral blood mononuclear cells (PBMC) from SLE patients were collected. Each sample was equally divided into four groups for the cell culture in 96 well plates. Specific siRNA for OAZ and GAPDH were concordantly added to experimental group and positive control group, while nonspecific siRNA was added to negative control group and only culture medium was added to Mock control group. Cells and supernatant were harvested after culturing for 72 hours, then RNA was extracted and reverse transcripted to cDNA. OAZ, Id1, Id2, Id3, Id4, LY6E mRNA expression levels were analyzed by real-time PCR. Levels of IFN-y, IL4, IL10, IL12, IL21, CCL2, ANA in supernatant were tested by ELISA. Relationships of the expression levels of OAZ mRNA with levels of cytokines and ANA were analyzed.
Part three:Human MSCs isolating and expanding from bone marrow cells or umbilical cord of healthy donors were infused into SLE patients. Peripheral blood cells were collected from 10 patients pre-MSCT as well as 1 week and 4 week post-MSCT, and RNA was extracted and reverse transcripted to cDNA. mRNA expression levels of OAZ and Idl-3 were measured by real-time PCR. Serum levels of IL10, IL12, IL21, CCL2 and ANA were tested by ELISA. Relationships of the gene expression levels with the levels of cytokines and ANA were analyzed.
Results Part one:The expression levels of OAZ, Id3, LY6E mRNA(ACt) in the bone marrow (10.6±0.5,5.8±3.2) and peripheral blood (14.1±2.7,7.5±1.8) of SLE patients were significantly increased than those observed in normal controls (16.5±0.9,10.4±2.6, 16.1±2.2，9.5±1.7), which was found to negatively correlate with SLEDAI score, renal lesion index, titers of anti-dsDNA and anti-RNA antibodies, but positively correlate with serum complement C3. Expression levels of BMP4 and BMP6 were differentially expressed in peripheral blood cells but not bone marrow progenitor cells.
Part two:OAZ, Id1, Id2, Id3, LY6E gene mRNA expression levels (△Ct:12.5±1.4, 8.9±1.5,4.3±0.8,8.0±1.1) in experimental group were significantly decreased comparing to those in negative control group (△Ct:10.2±1.1,6.5±1.2,2.4±1.3,6.2±1.2 respectively, p< 0.05). Levels of IFN-y, IL10, IL12, IL21 and ANA in experimental group were significantly lower than those in negative control group (p< 0.05); while level of CCL2 was higher than the negative control group (p<0.05). Difference of OAZ mRNA expression levels (△△Ct) between experimental group and negative control group were negatively correlated with changes of ANA, IL21 levels, but positively correlated with changes of Thl/Th2, CCL2.
Part three:mRNA expression levels of OAZ, Idl and Id3 gene in patients with SLE were significantly decreased 1 week (△Ct:12.4±1.1、9.7±1.9、9.7±1.9、2.1±1.0) and 4week (△Ct: 13.3±1.2,10.4±1.5、10.8±1.2、2.1±1.2) after MSCT comparing to those pre-MSCT (△Ct: 11.0±0.9、7.4±2.1、7.8±2.1、0.1±1.5 respectively, p all< 0.05). Levels of IL10, IL21 and ANA were significantly lower 4 week post-MSCT than those before (p< 0.05); while level of CCL2 was higher than pre-MSCT (p<0.05). Cytokines and ANA levels 1 week after MSCT were not differentially changed comparing to those pre-MSCT. Alteration of OAZ mRNA expression levels pre-and post-MSCT were negatively correlated with changes of ANA, IL21 levels and positively correlated with changes of IL12/IL10 and CCL2 levels.
Conclusion 1. OAZ pathway is involved in the pathogenesis of SLE.
2:OAZ siRNA can effectively reduce the expression of genes involving in the OAZ signaling pathway in SLE. OAZ may lead to abnormal production of ANA via regulating Id genes and cytokines.
3:The expression of genes involving in the OAZ signaling pathway was effectively reduced along with the alteration of several cytokines and ANA after allogeneic MSCT in SLE patients. OAZ signaling pathway could play an important role in MSCT treatment for SLE.
方法：实验一：收集SLE患者和正常对照骨髓前体细胞(各5例),提取RNA,逆转录为cDNA,加入相应的引物、SYBR Green I在ABI Prism 7500型高通量荧光定量仪上进行实时荧光定量PCR,采用看家基因酸性核糖体磷蛋白大亚基(RPLPO)进行标化,观察OAZ、Id3、BMP4、BMP6、Smad6、EHZF、LY6E基因的表达量与SLE疾病活动相关指标关系。同时收集30例SLE患者和20例正常人外周血细胞,对上述结果进行验证。
实验二：采集并分离SLE患者外周血单个核细胞,分为实验组、阳性对照组、阴性对照组和空白对照组进行细胞培养。实验组和阳性对照组分别用OAZ和GAPDH小干扰RNA(siRNA)在体外对培养细胞进行干扰,阴性对照组采用无关RNA序列,空白对照组为培养基对照。72小时后分离细胞和上清液,从细胞中提取RNA,逆转录为cDNA,用实时荧光定量PCR分析不同分组OAZ信号通路相关基因OAZ、Id1、Id2、Id3、Id4mRNA表达水平的变化。ELISA法测定上清液中IFN-γ、IL4、IL10、IL12、IL21、CCL2、ANA浓度,并分析这些因子分泌水平与OAZ基因表达的相关性。
实验三：从骨髓或脐带血中分离培养间充质干细胞(MSC)移植治疗10例SLE患者,采集并分离移植前、移植后1周、4周患者外周血有核细胞,从细胞中提取RNA,逆转录为cDNA,用实时荧光定量PCR技术分析不同分组OAZ信号通路相关基因OAZ、Id1、Id2、Id3 mRNA表达水平的变化。ELISA法测定移植前后患者血清中IL10、IL12、IL21、CCL2、ANA浓度,并分析这些因子分泌水平与OAZ基因表达的相关性。
结果：实验一：SLE患者骨髓前体细胞OAZ、Id3基因的mRNA表达水平(△Ct分别为10.6±0.5、5.8±3.2)较正常对照组(△Ct分别为16.5±0.9、10.4±2.6)显著增高,且表达水平高于外周血细胞；BMP6、BMP4基因表达水平虽较正常对照有高表达趋势,但差异无统计意义。SLE患者外周血细胞OAZ、Id3、BMP4、BMP6mRNA基因表达(△Ct分别为14.1±2.7、7.5±1.8、7.6±3.3、5.2±2.2)均显著高于正常(△Ct分别为16.1±2.2、9.5±1.7、9.7±0.3、6.4±1.2)。骨髓前体细胞OAZ、BMP6、BMP4、Id3的表达水平ACt值与SLEDAI积分、肾脏损伤指数、抗双链DNA (dsDNA)抗体、RNA相关抗体水平呈负相关；与补体C3呈正相关。
实验二：实验组OAZ、Id1、Id2、Id3基因的mRNA表达水平(△Ct分别为12.5±1.4、8.9±1.5、4.3±0.8、8.0±1.1)较阴性对照组(△Ct分别为10.2±1.1、6.5±1.2、2.4±1.3、6.2±1.2)显著降低(P<0.05)；Id4表达水平虽较阴性对照组有低表达趋势,但差异无统计学意义。实验组IFN-γ、IL10、IL12、IL21、ANA的水平明显低于阴性对照组；而CCL2高于阴性对照组(P<0.05)。实验组与阴性对照组OAZ mRNA表达水平△△Ct值与ANA的OD比值、IL21浓度比值呈负相关；与Th1/Th2、CCL2比值呈正相关。
实验三：移植后1周、4周OAZ、Id1、Id3基因的mRNA表达水平[ACt(1周)分别为12.4±1.1、9.7±1.9、9.7±1.9、2.1±1.0；△Ct(4周)分别为13.3±1.2、10.4±1.5、10.8±1.2、2.1±1.2]较移植前(△Ct分别为11.0±0.9、7.4±2.1、7.8±2.1、0.1±1.5)均显著降低(P<0.05)；Id2表达水平虽较移植前有低表达趋势,但差异无统计学意义。移植4周后IL10、IL21、ANA的水平明显低于移植前,IL12／IL10、CCL2高于移植前(P<0.05),但移植后1周的水平较移植前没有差异。移植前与移植后4周OAZ mRNA表达水平变化与ANA的OD值和IL21浓度比值呈负相关；与IL12/IL10、CCL2比值呈正相关。
结论：一：OAZ通路相关基因在SLE中异常表达,与疾病发生相关。
二：OAZ基因沉默可有效降低狼疮外周血单个核细胞中OAZ信号通路相关基因表达,同时减低多种细胞因子及抗核抗体水平,推测OAZ可能通过Id基因影响细胞因子的水平并导致ANA异常表达。
三：同种异体MSC移植治疗SLE可降低患者外周血中OAZ信号通路相关基因表达,同时减低多种细胞因子及抗核抗体水平,推测OAZ信号通路是MSC移植治疗SLE有效机制之一。
Objective To investigate the function of genes involved in OAZ signaling pathway in the patients with systemic lupus erythematosus (SLE)
Methods Part one:The expression levels of OAZ, BMP6, BMP4, Id3, Smad6, EHZF、LY6E genes were valuated in bone marrow progenitor cells of 5 SLE patients and 5 normal subjects and replicated in peripheral blood cells of 30 SLE patients and 20 normal individuals by real-time quantitative PCR technique. Relationships of the expression levels of OAZ, BMP6, BMP4, Id3、LY6E mRNA with disease activity and other clinical index were analyzed.
Part two:Peripheral blood mononuclear cells (PBMC) from SLE patients were collected. Each sample was equally divided into four groups for the cell culture in 96 well plates. Specific siRNA for OAZ and GAPDH were concordantly added to experimental group and positive control group, while nonspecific siRNA was added to negative control group and only culture medium was added to Mock control group. Cells and supernatant were harvested after culturing for 72 hours, then RNA was extracted and reverse transcripted to cDNA. OAZ, Id1, Id2, Id3, Id4, LY6E mRNA expression levels were analyzed by real-time PCR. Levels of IFN-y, IL4, IL10, IL12, IL21, CCL2, ANA in supernatant were tested by ELISA. Relationships of the expression levels of OAZ mRNA with levels of cytokines and ANA were analyzed.
Part three:Human MSCs isolating and expanding from bone marrow cells or umbilical cord of healthy donors were infused into SLE patients. Peripheral blood cells were collected from 10 patients pre-MSCT as well as 1 week and 4 week post-MSCT, and RNA was extracted and reverse transcripted to cDNA. mRNA expression levels of OAZ and Idl-3 were measured by real-time PCR. Serum levels of IL10, IL12, IL21, CCL2 and ANA were tested by ELISA. Relationships of the gene expression levels with the levels of cytokines and ANA were analyzed.
Results Part one:The expression levels of OAZ, Id3, LY6E mRNA(ACt) in the bone marrow (10.6±0.5,5.8±3.2) and peripheral blood (14.1±2.7,7.5±1.8) of SLE patients were significantly increased than those observed in normal controls (16.5±0.9,10.4±2.6, 16.1±2.2，9.5±1.7), which was found to negatively correlate with SLEDAI score, renal lesion index, titers of anti-dsDNA and anti-RNA antibodies, but positively correlate with serum complement C3. Expression levels of BMP4 and BMP6 were differentially expressed in peripheral blood cells but not bone marrow progenitor cells.
Part two:OAZ, Id1, Id2, Id3, LY6E gene mRNA expression levels (△Ct:12.5±1.4, 8.9±1.5,4.3±0.8,8.0±1.1) in experimental group were significantly decreased comparing to those in negative control group (△Ct:10.2±1.1,6.5±1.2,2.4±1.3,6.2±1.2 respectively, p< 0.05). Levels of IFN-y, IL10, IL12, IL21 and ANA in experimental group were significantly lower than those in negative control group (p< 0.05); while level of CCL2 was higher than the negative control group (p<0.05). Difference of OAZ mRNA expression levels (△△Ct) between experimental group and negative control group were negatively correlated with changes of ANA, IL21 levels, but positively correlated with changes of Thl/Th2, CCL2.
Part three:mRNA expression levels of OAZ, Idl and Id3 gene in patients with SLE were significantly decreased 1 week (△Ct:12.4±1.1、9.7±1.9、9.7±1.9、2.1±1.0) and 4week (△Ct: 13.3±1.2,10.4±1.5、10.8±1.2、2.1±1.2) after MSCT comparing to those pre-MSCT (△Ct: 11.0±0.9、7.4±2.1、7.8±2.1、0.1±1.5 respectively, p all< 0.05). Levels of IL10, IL21 and ANA were significantly lower 4 week post-MSCT than those before (p< 0.05); while level of CCL2 was higher than pre-MSCT (p<0.05). Cytokines and ANA levels 1 week after MSCT were not differentially changed comparing to those pre-MSCT. Alteration of OAZ mRNA expression levels pre-and post-MSCT were negatively correlated with changes of ANA, IL21 levels and positively correlated with changes of IL12/IL10 and CCL2 levels.
Conclusion 1. OAZ pathway is involved in the pathogenesis of SLE.
2:OAZ siRNA can effectively reduce the expression of genes involving in the OAZ signaling pathway in SLE. OAZ may lead to abnormal production of ANA via regulating Id genes and cytokines.
3:The expression of genes involving in the OAZ signaling pathway was effectively reduced along with the alteration of several cytokines and ANA after allogeneic MSCT in SLE patients. OAZ signaling pathway could play an important role in MSCT treatment for SLE.
引文
1 Zhang J, Roschke V, Baker KP, et al. Cutting edge:a role for B lymphocyte stimulator in systemic lupus erythematosus. J Immunol,2001,166:6-10.
2 Schiemann B, Gommerman JL, Vora K, et al. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science,2001,293:2111-4.
3 Majumdar MK, Thiede MA, Mosca JD, et al. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSC) and stromal cells. J Cell Physiol,1998,176(1):57-66.
4 Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol,1999,181(1):67-73.
5 Koc ON, Gerson SL, Cooper BW, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol,2000,18(2):307-316.
6 Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science,1999,284(5411):143-147.
7 Schuening FG, Storb R, Meyer J, et al. Long-term culture of canine bone marrow cells. Exp Hematol, 1989,17(5):411-417.
8 Cheng L, Qasba P, Vanguri P, et al. Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34(+) hematopoietic progenitor cells. J Cell Physiol, 2000,184(1):58-69.
9 Peled A, Petit I, Kollet O, et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science,1999,283(5403):845-848.
10 Bhakta S, Hong P, Koc O. The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovasc Revasc Med,2006,7(1):19-24.
11 Liu G, Hu YY, Zhao JN, et al. Effect of type I collagen on the adhesion, proliferation, and osteoblastic gene expression of bone marrow-derived mesenchymal stem cells. Chin J Traumatol, 2004,7(6):358-362.
12 Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 2002,99(10):3838-3843.
13 Tse WT, Pendleton JD, Beyer WM, et al. Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation. Transplantation,2003,75(3):389-397.
14 Le Blanc K, Tammik L, Sundberg B, et al. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol,2003,57(1):11-20.
15 Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood,2003,102(10):3837-3844.
16 Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol,2002,30(1):42-48.
17 Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet,2004,363(9419):1439-1441.
18 Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol,2003,31(10):890-896.
19李慧,梁军,孙凌云,等.NZBWF1/J鼠骨髓间充质干细胞对T淋巴细胞的免疫调节.中华风湿病学杂志,2006,10：457-461.
20 Panagiota A, Sonia A, Angelos D, et al. Interactions between human mesenchymal stem cells and natural killer cells.Stem Cells,2006,24:74-85.
21张华勇,冯学兵,孙凌云.系统性红斑狼疮患者间质干细胞生物学特性及对造血支持的研究.中华风湿病学杂志,2006,10：331-334.
22 Bernasconi NL, Onai N, Lanzavecchia A. A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells.Blood,2003,101:4500-4504.
23 Jiang XX, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dentritic cells.Blood,2005,105:4120-4126.
24郭根凯,梁军,侯亚义.系统性红斑狼疮患者骨髓间质干细胞对B淋巴细胞免疫抑制作用的初步研究.中华风湿病学杂志,2007(11)：524-527.
25 Anna C, Federica B, Elisa F, et al. Human mesenchymal stem cells modulate B-cell functions.Blood,2006,107:367-372.
26 Sato Y, Araki H, Kato J, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood,2005,106:756-763.
27 Zhao LR, Duan WM, Reyes M, et al. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol,2002, 174:11-20.
28 Zhang J, Li Y, Chen J, et al. Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. Exp Neurol,2005,195:16-26.
29 Togel F, Hu Z, Weiss K, et al. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol,2005, 289:F31-F42.
30 Kunter U, Rong S, Djuric Z, et al. Transplanted mesenchymal stem cells accelerate glomerular healing in experimental glomerulonephritis. J Am Soc Nephrol,2006,17:2202-2212.
31 Morton JI, Siegel BV. Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice. Proc Natl Acad Sci USA,1974,71(6):2162-2165.
32 Ikehara S, Good RA, Nakamura T, et al. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA,1985,82(8):2483-2487.
33 Ikehara S, Inaba M, Yasumizu R, et al. Autoimmune diseases as stem cell disorders. Tohoku J Exp Med,1994,173(1):141-155.
34孙凌云.自身免疫病一造血干细胞病.中华风湿病学杂志,2000,4(1)：5-6.
35 Sun L Y, Li H, Liang J, et al. The polarization of T lymphocytes modulated by mesenchymal stem cells in NZB/WF1 and BALB/C mice. Int J Mol Sci,2007,8:455-469.
36 Jabs DA, Burek CL, Hu Q, et al. Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice. Cell Immunol,1992,141:496-507.
37 Tsai CY, Wu TH, Huang SF, et al. Abnormal splenic and thymic IL-4 and TNF-alpha expression in MRL-lpr/lpr mice. Scand J Immunol,1995,41:157-163.
38 Prud'homme GJ, Kono DH, Theofilopoulos AN. Quantitative polymerase chain reaction analysis reveals marked overexpression of interleukin-1 beta, interleukin-1 and interferon-gamma mRNA in the lymph nodes of lupus-prone mice. Mol Immunol,1995,32:495-503.
39 Peng SL, Moslehi J, Craft J. Roles of interferon-gamma and interleukin-4 in murine lupus. J Clin Invest,1997,99:1936-1946.
40 Nicoletti F, Meroni P, Dimarco R, et al. In vivo treatment with a monoclonal antibody to interferongamma neither affects the survival nor the incidence of lupusnephritis in the MRL-lpr/lpr mouse. Immunopharmacology,1992,24:11-16.
41 Shimizu S, Sugiyama N, Masutani K, et al. Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1). J Immunol,2005, 175:7185-7192.
42 Jabs DA, Lee B, Whittum-Hudson JA, et al. Thl versus Th2 immune responses in autoimmune lacrimal gland disease in MRL/Mp mice. Invest Ophthalmol Vis Sci,2000,41:826-831.
43 Schwarting A, Moore K, Wada T, et al. IFN-gamma limits macrophage expansion in MRL-Fas(lpr) autoimmune interstitial nephritis:a negative regulatory pathway. J Immunol,1998,160:4074-4081.
44张华勇,冯学兵,马晓蕾,等.异基因骨髓间充质干细胞移植治疗系统性红斑狼疮11例临床分析.中华风湿病学杂志,2009,13：89-92.
45 Lazzari L, Lucchi S, Rebulla P, et al. Long-term expansion and maintenance of cord blood haematopoietic stem cells using thrombopoietin, Flt3-ligand, interleukin (IL)-6 and IL-11 in a serum-free and stroma-free culture system. Br J Haematol,2001,112(2):397-404.
46 Biesecker LG, Emerson SG. Interleukin-6 is a component of human umbilical cord serum and stimulates hematopoiesis in embryonic stem cells in vitro. Exp Hematol,1993,21(6):774-778.
47 Armitage RJ, Namen AE, Sassenfeld HM, et al. Regulation of human T cell proliferation by IL-7. J Immunol,1990,144(3):938-941.
48 Fry TJ, Mackall CL. The many faces of IL-7:from lymphopoiesis to peripheral T cell maintenance. J Immunol,2005,174(11):6571-6576.
49 Kurzrock R. Thrombopoietic factors in chronic bone marrow failure states:the platelet problem revisited. Clin Cancer Res,2005,11(4):1361-1367.
50 Minehata K, Mukouyama YS, Sekiguchi T, et al. Macrophage colony stimulating factor modulates the development of hematopoiesis by stimulating the differentiation of endothelial cells in the AGM region. Blood,2002,99(7):2360-2368.
51 Thomas D, Vadas M, Lopez A. Regulation of haematopoiesis by growth factors-emerging insights and therapies. Expert Opin Biol Ther,2004,4(6):869-879.
52 Lyman SD, Jacobsen SE. c-kit ligand and Flt3 ligand:stem/progenitor cell factors with overlapping yet distinct activities. Blood,1998,91(4):1101-1134.
53 Arrighi JF, Hauser C, Chapuis B, et al. Long-term culture of human CD34(+) progenitors with FLT3-ligand, thrombopoietin, and stem cell factor induces extensive amplification of a CD34(-)CD14(-) and a CD34(-)CD14(+) dendritic cell precursor. Blood,1999,93(7):2244-2252.
54 Luens KM, Travis MA, Chen BP, et al. Thrombopoietin, kit ligand, and flk2/flt3 ligand together induce increased numbers of primitive hematopoietic progenitors from human CD34+Thy-1+Lin-cells with preserved ability to engraft SCID-hu bone. Blood,1998,91(4):1206-1215.
55 Gaffney PM, Ortmann WA, Selby SA, et al. Genome screening in human systemic lupus erythematosus:results from a second Minnesota cohort and combined analyses of 187 sib-pair families. Am J Hum Genet.2000,66:547-556.
56 International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley JB, Alarcon-Riquelme ME, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008,40:204-210.
57 Hom G, Graham RR, Modrek B, et al. Association of systemic lupus erythematosus with C8 or f13-BLK and ITGAM-ITGAX. N Engl J Med.2000,358:900-909.
58冯学兵,沈南,陈顺乐,等。中国人群16号染色体q12区存在SLE易感基因。中华医学遗传学杂志2003,20：27-30.
59冯学兵,沈南,罗纬琼,等。系统性红斑狼疮患者16q12精细定位研究。中华风湿病学杂志2004,8：454-457.
60冯学兵,沈南,罗纬琼,等。中国人群系统性红斑狼疮患者OAz基因多态性研究。中华医学遗传学学杂志2004,21：430-434.
61 Gillett CD, Langefeld CD, Williams AH, et al. Fine mapping chromosome 16q12 in a collection of 231 systemic lupus erythematosus sibpair and multiplex families. Genes Immun.2005,6:19-23.
62 Nath SK, Namjou B, Hutchings D, et al. Systemic lupus erythematosus (SLE) and chromosome 16: confirmation of linkage to 16q12-13 and evidence for genetic heterogeneity. Eur J Hum Genet.2004, 12:668-672.
63 Lee YH, Nath SK. Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. Hum Genet.2005,118:434-443.
64 Cantor RM, Yuan J, Napier S, et al. Systemic lupus erythematosus genome scan:support for linkage at 1q23,2q33,16q12-13, and 17q21-23 and novel evidence at 3p24,10q23-24,13q32, and 18q22-23. Arthritis Rheum.200,50:3203-3210.
65 Ath SK, Han S, Kim-Howard X, et al. A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet.2008,40:152-154.
66 Wrana JL. Regulation of Smad activity. Cell,2000,100:189-192.
67 Scott Fields, Kristina Ternyak, Hua Gao, et al. The'zinc knuckle'motif of early B cell factor is required for transcriptional activation of B cell-specific genes. Molecular Immunol,2008,45:3786-3796.
68 Bond HM, Mesuraca M, Carbone E, et al. Early hematopoietic zinc finger protein (EHZF), the human homologue to mouse Evi3, is highly expressed in primitive human hematopoietic cells. Blood,2004, 103:2062-2070.
69 Zon LI. Self-renewal versus differentiation, a job for the mighty morphogens. Nat Immunol 2001, 2:142-143.
70 Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003,425:836-841.
71 Heasley LE, Petersen BE. Signalling in stem cells. EMBO Rep 2004,5:241-244.
72 Manching Ku, Shavonne Howard, Weihua Ni, et al.OAZ regulates bone morphogenetic protein signaling through Smad6 activation. J Biol Chem,2006,281:5277-5287.
73 Davis BN, Hilyard AC, Lagna G, Hata et al. A SMAD proteins control DROSHA-mediated microRNA maturation. Nature,2008,454:56-61.
74 Jonas Larsson, Stefan Karlsson. The role of Smad signaling hematopoiesis. Oncogene,2005, 24:5676-5692.
75 Andreas von Bubnoff, Daniel A. Peiffer, Ira L. Blitz, et al.Phylogenetic footprinting and genome scanning identify vertebrate BMP response elements and new target genes. Developmental Biology, 2005,281:210-226.
76 Christian Kersten, Guri Dosen, June H. Myklebust, et al.BMP-6 inhibits human bone marrow B lymphopoiesisd Upregulation of Id1 and Id3. Exp Hematol,2006,34:72-81.
1 冯学兵,沈南,罗纬琼,等.系统性红斑狼疮患者16q12精细定位研究.中华风湿病学杂志,2004,8：454-457.
2 Bombardier C, Gladman DD, Urowitz MB, et al. Derivation of the SLEDAI:a disease activity index for lupus patients:the committee on prognosis studies in SLE. Arthritis Rheum,1992,35:630-640.
3 Arnett FC, Edworthy SM, Bloch DA, et al.The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum,1988,31:315-324.
4 Feng X, Wu H, Grossman JM, et al. Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheum,2006, 54:2951-62.
5 Pitashny M, Schwartz N, Qing X, et al. Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis. Arthritis Rheum,2007,56:1894-903.
6 Muro Y. Antinuclear antibodies. Autoimmunity,2005,38:3-9.
7 冯学兵,沈南,陈顺乐,等.中国人群16号染色体q12区存在SLE易感基因.中华医学遗传学杂志,2003,20：27-30.
8 冯学兵,沈南,陈顺乐,等.系统性红斑狼疮患者16号染色体候选基因表达研究.中华皮肤科杂志,2003,36：322-324.
9 Liang D, Huang XQ, Shen N, et al. Variations within OLF1/EBF-associated zinc finger protein gene confer susceptibility to lupus nephritis in Chinese population. Zhonghua yi Xue Za Zhi,2005,85:949-54.
10 Wrana JL. Regulation of Smad activity. Cell,2000,100:189-192.
11 Scott Fields, Kristina Ternyak, Hua Gao, et al. The'zinc knuckle'motif of early B cell factor is required for transcriptional activation of B cell-specific genes. Mol Immunol,2008,45:3786-96.
12 Bond HM, Mesuraca M, Carbone E, et al. Early hematopoietic zinc finger protein (EHZF), the human homologue to mouse Evi3, is highly expressed in primitive human hematopoietic cells. Blood,2004,103: 2062-70.
13 Zon LI. Self-renewal versus differentiation, a job for the mighty morphogens. Nat Immunol 2001, 2:142-143.
14 Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003,425:836-841.
15 Heasley LE, Petersen BE. Signalling in stem cells:meeting on signal transduction determining the fate of stem cells.EMBO Rep 2004,5:241-244.
16 Manching Ku, Shavonne Howard, Weihua Ni, et al.OAZ regulates bone morphogenetic protein signaling through Smad6 activation. J Biol Chem,2006,281:5277-5287.
17 Davis BN, Hilyard AC, Lagna G, et al. SMAD proteins control DROSHA-mediated microRNA maturation. Nature,2008,454:56-61.
18 Jonas Larsson, Stefan Karlsson. The role of Smad signaling hematopoiesis. Oncogene,2005,24:5676-92.
19 Andreas von Bubnoff, Daniel A. Peiffer, Ira L. Blitz, et al.Phylogenetic footprinting and genome scanning identify vertebrate BMP response elements and new target genes. Dev Biol,2005,281:210-226.
20 Christian Kersten, Guri Dosen, June H. Myklebust, et al.BMP-6 inhibits human bone marrow B lymphopoiesisd Upregulation of Id1 and Id3. Exp Hematol,2006,34:72-81.
1 冯学兵,沈南,罗纬琼,等.系统性红斑狼疮患者16q12精细定位研究.中华风湿病学杂志,2004,8：454-457.
2 Shim S, Bae N, Han JK. Bone morphogenetic protein-4-induced activation of Xretpos is mediated by Smads and Olf-1/EBF associated zinc finger (OAZ). Nucleic Acids Res 2002; 30:3107-3017.
3 李荣良,黄静,孙凌云,等.系统性红斑狼疮OAZ通路基因表达研究.中华医学杂志,2009,89：2068-2071.
4 Bombardier C, Gladman DD, Urowitz MB, et al. Derivation of the SLEDAI:a disease activity index for lupus patients, the committee on prognosis studies in SLE. Arthritis Rheum,1992,35:630-640.
5 Feng X, Wu H, Grossman JM, et al. Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheum,2006, 54:2951-62.
6 冯学兵,沈南,陈顺乐,等.中国人群16号染色体q12区存在SLE易感基因.中华医学遗传学杂志,2003,20：27-30.
7 冯学兵,沈南,陈顺乐,等.系统性红斑狼疮患者16号染色体候选基因表达研究.中华皮肤科杂志,2003,36：322-324.
8 Wrana JL. Regulation of Smad activity. Cell,2000,100:189-192.
9 Benezra R, Davis RL, Lockshon D, et al. The protein Id:a negative regulator of helix-loop-helix DNA binding proteins. Cell,1990,61:49-59.
10 Massari ME, Murre C. Helix-loop-helix proteins:regulators of transcription in eucaryotic organisms. Mol Cell Biol,2000,20:429-440.
11 Rivera R, Murre C. The regulation and function of the Id proteins in lymphocyte development. Oncogene, 2001,20:8308-8316.
12 Mori S, Nishikawa SI, Yokota Y. Lactation defect in mice lacking the helix-loop-helix inhibitor Id2. EMBOJ,2000,19:5772-5781.
13周琳,屠小刚,朱烨,等.系统性红斑狼疮患者血清B淋巴细胞刺激因子水平的检测.中华风湿病杂,2005,9(4)：222-224.
14李慧,梁军,侯亚义,等.NZBWF1/J鼠骨髓间充质干细胞对淋巴细胞亚群平衡的免疫调节.中华风湿病学杂志,2006,10：457-461.
15 Parrish-Novak J, Dillon SR, Nelson A, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature,2000,408:57-63.
16 Ozaki K, Spolski R, Ettinger R, et al. Regulation of B cell differentiation and plasma cell generation by IL21, a novel inducer of Blimp-land Bcl-6. J Immunol,2004,173:5361-5371.
17 Ozaki K, Spolski R, Feng CG, et al. A critical role for IL-21 in regulating immunoglobulin production. Science,2002,298:1630-1634.
18 Pene J, Gauchat JF, Lecart S, et al. Cutting edge:IL-21 is a switch factor for the production of IgGl and IgG3 by human B cells. J Immunol,2004,172:5154-5157.
19 Herber D, Brown TP, Liang S. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. J Immunol.2007,178,3822-3830.
20 Rafei M, Hsieh J, Fortier S, et al. Mesenchymal stromal cell_derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction. Blood,2008,112:4991-4998.
1 冯学兵,沈南,罗纬琼,等.系统性红斑狼疮患者16q12精细定位研究.中华风湿病学杂志,2004,8：454-457.
2 Shim S, Bae N, Han JK. Bone morphogenetic protein-4-induced activation of Xretpos is mediated by Smads and Olf-1/EBF associated zinc finger (OAZ). Nucleic Acids Res 2002; 30:3107-3017.
3 李荣良,黄静,孙凌云,等.系统性红斑狼疮OAZ通路基因表达研究.中华医学杂志,2009,89：2068-2071.
4 黄静,李荣良,冯学兵,等.系统性红斑狼疮干扰素诱导基因表达研究.中华内科学杂志,2010,49：45-48.
5 李荣良,黄静,周涛,等.siRNA阻断OAZ信号通路对狼疮抗核抗体产生的影响.中华风湿病学杂志,2010,14：3-7.
6 Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum,1997,40:1725.
7 张华勇,冯学兵,马晓蕾,等.异基因骨髓间充质干细胞移植治疗系统性红斑狼疮11例临床分析.中华风湿病学杂志,2009,13：89-92.
8 Morton JI, Siegel BV. Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice. Proc Natl Acad Sci U S A,1974,71(6):2162-2165.
9 Ikehara S, Good RA, Nakamura T, et al. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA,1985,82(8):2483-2487.
10 Ikehara S, Inaba M, Yasumizu R, et al. Autoimmune diseases as stem cell disorders. Tohoku J Exp Med, 1994,173(1):141-155.
11孙凌云.自身免疫病一造血干细胞病.中华风湿病学杂志,2000,4(1)：5-6.
12 El-Badri NS, Pascual C, Ferrari A, et al. Abnormalities of stromal cells in autoimmune systemic lupus murine model. Blood,2004,104:364A.
13顾志峰,赵盛楠,张华勇,等.系统性红斑狼疮患者骨髓MSC超微结构及细胞骨架特征.中华风湿病学杂志,2008,12：397-400.
14 Sun LY, Zhang HY, Feng XB, et al. Abnormality of bone marrow-derived stem cell in patients with systemic lupus erythematosus. Lupus.2007,16:121-128.
15 Sun L Y, Li H, Liang J, et al. The polarization of T lymphocytes modulated by mesenchymal stem cells in NZB/WF1 and BALB/C mice. Int J Mol Sci,2007,8:455-469.
16 Wrana JL. Regulation of Smad activity. Cell,2000,100:189-192.
17 Benezra R, Davis RL, Lockshon D, et al. The protein Id:a negative regulator of helix-loop-helix DNA binding proteins. Cell,1990,61:49-59.
18 Massari ME, Murre C. Helix-loop-helix proteins:regulators of transcription in eucaryotic organisms. Mol Cell Biol,2000,20:429-440.
19 Rivera R, Murre C. The regulation and function of the Id proteins in lymphocyte development. Oncogene, 2001,20:8308-8316.
20 Mori S, Nishikawa SI, Yokota Y. Lactation defect in mice lacking the helix-loop-helix inhibitor Id2. EMBO J,2000,19:5772-5781.
21汤建平,顾越英,沈南,等.干扰素诱导表达的淋巴细胞抗原6复合体E和干扰素诱导蛋白1基因与系统性红斑狼疮患者病情活动性的关系.中华医学杂志,2004,84：1157-1160.
22 Herber D, Brown TP, Liang S. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. J Immunol.2007,178,3822-3830.
23李慧,梁军,侯亚义,等.NZBWF1/J鼠骨髓间充质干细胞对淋巴细胞亚群平衡的免疫调节.中华风湿病学杂志,2006,10：457-461.
24 Rafei M, Hsieh J, Fortier S, et al. Mesenchymal stromal cell derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction. Blood,2008,112:4991-4998.
1 Hofman RW. T cells in the pathogenesis of systemic lupus erythematosus. Clin Immunol,2004,113:4-13.
2 栾希英,张光波,胡玉敏,等.人骨髓MSC对PHA活化T细胞周期以及表型和细胞因子分泌的影响.细胞与分子免疫学杂志,2007,23：402-405.
3 Groh ME, Maitra B, Szekely E, et al. Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol,2005,33:928-934.
4 李慧,梁军,孙凌云,等.NZBWF1/J鼠骨髓间充质干细胞对T淋巴细胞亚群平衡的免疫调节.中华风湿病学杂志,2006,10：457-461.
5 Rasmusson I, Ringden O, Sundberg B, et al. Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res,2005,305:33-41.
6 Sbano P, Cuccia A, Mazzanti B, et al.Use of donor bone marrow mesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model. Arch Dermatol Res,2008,300:115-24.
7 Plumas J, Chaperot L, Richard MJ, et a 1. Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia,2005,19:1597-1604.
8 Djouad F, Plence P, Bony C, et al.Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood,2003,102:3837-3844.
9 Krampers M, Glennie S, Dyson J, et al. Bone marrow mesenchymal stem cells inhibit the response of native and memory antigen specific T cells to their congnate peptide. Blood,2003,101:3722-3729.
10 Di Nicola M, Carlo Stella C, Magni M, et al. Human bone marrow stromal cells suppress T lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood,2002,99:3838-3843.
11 Zappia E, Casazza S, Pedemonte E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T cell anergy. Blood,2005,106:1755-1761.
12 Chabannes D, Hill M, Merieau E, et al. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood,2007,110:3691-3694.
13 Krampera M, Cosmi L, Angeli R, et al. Role of the IFN-y in the immunomodulatory activity of human mesenchymal stem cells. Stem cells,2005,24:386-398.
14 Sotiropoulou PA, Perez SA, Gritzapis AD, et al. Interactions between human mensenchymal stem cells and natural killer cells. Stem Cells,2006,24:74-85.
15张伟,葛薇,李长红,等.骨髓间充质干细胞通过上调CD8+ CD28T细胞抑制T细胞的增殖.中国实验血液学杂志,2004,12：666-669.
16 Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood,2005,105:1815-1822.
17孙凌云,顾宁琰,侯亚义,等.系统性红斑狼疮骨髓间质干细胞的初步研究.中华风湿病学杂志,2005,9：586-589.
18 Papadaki HA, Boumpas DT, Gibson FM, et al. Increased apoptosis of bone marrow CD34+ cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus. Br J Haematol,2001,115:167-174.
19 El-Badri NS, Pascual C, Ferrari A, et al. Abnormalities of stromal cells in autoimmune systemic lupus murine model. Blood,2004,104:364A.
20顾志峰,赵盛楠,张华勇,等.系统性红斑狼疮患者骨髓MSC超微结构及细胞骨架特征.中华风湿病学杂志,2008,12：397-400.
21李慧,孙凌云.MRL/lpr鼠骨髓间充质干细胞对T淋巴细胞作用的研究.中华风湿病学杂志,2007,11：340-343.
22 Lee JH, Wang LC, Lin YT, et al. Inverse correlation between CD4 regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus. Immunol,2006,117: 280-286.
23 Miyara M, Amoura Z, Parizot C, et al. Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol,2005,175:8392-8400.
24 Filaci G, Bacilieri S, Fravega M, et al. Impairment of CD8+ T suppressor cell function in patients with active systemic lupus erythematosus. J Immnol,2001,166:6452-6457.
25 Funauchi M, Sugiyama M, Sukyoo B, et al. A possible role of apoptosis for regulating autoreactive responses in systemic lupus erythematosus. Lupus,2001,10:284-288.
26顾志峰,金欧阳,徐婷,等.脐带间质干细胞移植治疗狼疮鼠的疗效.中华风湿病学杂志,2009,13：4-7.
27 Zhou K, Zhang H, Jin O, Feng X, Yao G, Hou Y, Sun L. Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice. Cell Mol Immunol, 2008,5:417-424.
28 Sun L Y, Li H, Liang J, et al. The polarization of T lymphocytes modulated by mesenchymal stem cells in NZB/WF1 and BALB/C mice. Int J Mol Sci,2007,8:455-469.
29赵盛楠,张华勇,顾志峰,等.间充质干细胞对系统性红斑狼疮CD4+ Foxp3+ T淋巴细胞的调节.中华风湿病学杂志,2008,12：7-10.
30孙凌云,张华勇,冯学兵,等.异基因骨髓间质干细胞移植治疗难治性红斑狼疮.实用临床医药杂志,2007,11：2-4.
[1]Sun L Y, Zhang H Y, Fen X B, et al. Abnormality of bone marrow-derived stem cell in patients with systemic lupus erythematosus. Lupus,2007,16(2):121.
[2]Remer CF, Weisman MH, Wallace DJ. Benefits of leflunomide in systemic lupus erythematosus:a pilot observational study. Lupus,2001,10:480-3.
[3]Mok CC, Tong KH, To CH, et al. Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: an open-labeled pilot study. Kidney Int,2005,68:813-7.
[4]Chan TM, Li FK, Tang CS, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med,2000,343:1156-62.
[5]Hu W, Liu Z, Chen H, et al. Mycophenolate mofetil vs cyclophosphamide therapy for patients with diffuse proliferative lupus nephritis. Chin Med J (Engl),2002,115:705-9.
[6]Alarcon-Segovia D, Tumlin JA, Furie RA, et al. LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus:results from a randomized, double-blind, placebo-controlled study. Arthritis Rheum,2003,48:442-54.
[7]Sfikakis PP, Boletis JN, Lionaki S, et al. Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand:an open-label trial. Arthritis Rheum,2005,52:501-13.
[8]Seshasayee D, Valdez P, Yan M, et al. Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor. Immunity,2003,18:279-88.
[9]Boumpas DT, Furie R, Manzi S, et al. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum,2003,48:719-27.
[10]Kalunian KC, Davis JC Jr, Merrill JT, et al. Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD 154:a randomized, double-blind, placebo-controlled trial. Arthritis Rheum,2002,46:3251-8.
[11]Larsen CP, Pearson TC, Adams AB, et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant,2005,5:443-53.
[12]Daikh DI, Wofsy D. Cutting edge:reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. J Immunol,2001,166:2913-6.
[13]Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science,1999,284(5411):143-147.
[14]Koc ON, Gerson SL, Cooper BW, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol,2000,18(2):307-316.
[15]Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood,2002,99(10):3838-3843.
[16]Tse WT, Pendleton JD, Beyer WM, et al. Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation. Transplantation,2003,75(3):389-397.
[17]Le Blanc K, Tammik L, Sundberg B, et al. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol,2003,57(1):11-20.
[18]Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals.Blood,2003,102(10):3837-3844.
[19]Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol,2002,30(1):42-48.
[20]Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet,2004,363(9419):1439-1441.
[21]Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol,2003,31(10):890-896.
[22]Morton JI, Siegel BV. Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice. Proc Natl Acad Sci USA,1974,71(6):2162-2165.
[23]Ikehara S, Good RA, Nakamura T, et al. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA,1985,82(8):2483-2487.
[24]Papadaki HA, Boumpas DT, Gibson FM, et al. Increased apoptosis of bone marrow CD34(+) cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus. Br J Haematol,2001,115(1):167-174.
[25]Ikehara S. New strategies for allogeneic BMT. Bone Marrow Transplant,2003,32 Suppl 1:S73-75.
[26]李慧,孙凌云.间质干细胞的免疫调节及免疫治疗作用研究.中华医学杂志,2006,86：501.
[27]Sun L Y, Li H, Liang J, et al, The polarization of T lymphocytes modulated by mesenchymal stem cells in NZB/WF1 and BALB/C mice. Int JMol Sci,2007,8:455.
[28]Ikehara S. New strategies for allogeneic BMT, Bone Marrow Transplant,2003,32:S73.
[29]孙凌云,张华勇,冯学兵,等.异基因骨髓间质干细胞移植治疗难治性红斑狼疮.实用临床医药杂志,2007,11(4)：2-4.
[30]董燕湘,董晓先,何慧华,等.大鼠骨髓间质干细胞用中药绞股蓝诱导为神经细胞的研究[J].中华神经科杂志,2003,36(5)：355.
[31]张进,徐志伟.补肾法诱导间充质干细胞向神经方向分化研究[J].现代医院,2004,4(9)：15.
[32]苏平,黄建华,雒晓东,等.银杏内酯B对骨髓间充质干细胞分化为神经样细胞的影响.广东医学,2007,28(1)：33-35.
[33]冼绍祥, 杨忠奇, 汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究.广州中医药大学学报,2007,24(1)：37-40.
[34]史风雷,李刚,王海彬,等.袁氏生脉成骨胶囊对激素诱导骨髓基质细胞成脂分化的拮抗作用[J].广州中医药大学学报,2003,20(4)：302.
[35]杨博华,秦建辉,朱龄群,等.自体骨髓干细胞移植合中药治疗下肢动脉缺血[J].浙江中西医结合杂志,2004,14(11)：683.
[1]Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science,1999,284(5411):143-147.
[2]贾正平,张汝学,等.淫羊藿总黄酮含药血清促进骨髓间充质干细胞增殖与成骨性分化.中国骨质疏松杂志,2004,10(4)：420-422.
[3]肖鲁伟,武中庆,季卫锋,等.右归饮诱导胎兔骨髓基质细胞向软骨细胞分化的实验研究.中国中医药科技,2005,12(3)：154.
[4]张进,徐志伟.补肾法诱导间充质干细胞向神经方向分化研究.现代医院,2004,4(9)：15.
[5]冼绍祥,杨忠奇,汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究.广州中医药大学学报,2007,24(1)：37-40.
[6]Majumdar MK, Thiede MA, Mosca JD, et al. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSC) and stromal cells. J Cell Physiol,1998,176(1):57-66.
[7]Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol,1999,181(1):67-73.
[8]Koc ON, Gerson SL, Cooper BW, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol,2000,18(2):307-316.
[9]张新华,黄有文,王荣新,等.益髓生血灵对小鼠骨髓造血干／祖细胞的影响.浙江中医杂志,2002,37(10)：448.
[10]陈志雄,曹克俭,薛恺睿,等.活髓片对环磷酰胺造模小鼠骨髓骨髓细胞DNA含量及细胞周期的影响.中医杂志,1999,40(11)：686.
[11]梁毅,陈志雄,丘和明,等.活髓片与四物汤对免疫介导再障小鼠骨髓基质细胞的影响比较.中国中西医结合急救杂志,2002,9(6)：327.
[12]Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood,2002,99(10):3838-3843.
[13]Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol,2002,30(1):42-48.
[14]Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet,2004,363(9419):1439-1441.
[15]Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol,2003,31(10):890-896.
[16]杨博华,秦建辉,朱龄群,等.自体骨髓干细胞移植合中药治疗下肢动脉缺血.浙江中西医结合杂志,2004,14(11)：683.
2 Schiemann B, Gommerman JL, Vora K, et al. An essential role for BAFF in the normal development of B cells through a BCMA-independent pathway. Science,2001,293:2111-4.
3 Majumdar MK, Thiede MA, Mosca JD, et al. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSC) and stromal cells. J Cell Physiol,1998,176(1):57-66.
4 Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol,1999,181(1):67-73.
5 Koc ON, Gerson SL, Cooper BW, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol,2000,18(2):307-316.
6 Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science,1999,284(5411):143-147.
7 Schuening FG, Storb R, Meyer J, et al. Long-term culture of canine bone marrow cells. Exp Hematol, 1989,17(5):411-417.
8 Cheng L, Qasba P, Vanguri P, et al. Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34(+) hematopoietic progenitor cells. J Cell Physiol, 2000,184(1):58-69.
9 Peled A, Petit I, Kollet O, et al. Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science,1999,283(5403):845-848.
10 Bhakta S, Hong P, Koc O. The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovasc Revasc Med,2006,7(1):19-24.
11 Liu G, Hu YY, Zhao JN, et al. Effect of type I collagen on the adhesion, proliferation, and osteoblastic gene expression of bone marrow-derived mesenchymal stem cells. Chin J Traumatol, 2004,7(6):358-362.
12 Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood, 2002,99(10):3838-3843.
13 Tse WT, Pendleton JD, Beyer WM, et al. Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation. Transplantation,2003,75(3):389-397.
14 Le Blanc K, Tammik L, Sundberg B, et al. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol,2003,57(1):11-20.
15 Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood,2003,102(10):3837-3844.
16 Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol,2002,30(1):42-48.
17 Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet,2004,363(9419):1439-1441.
18 Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol,2003,31(10):890-896.
19李慧,梁军,孙凌云,等.NZBWF1/J鼠骨髓间充质干细胞对T淋巴细胞的免疫调节.中华风湿病学杂志,2006,10：457-461.
20 Panagiota A, Sonia A, Angelos D, et al. Interactions between human mesenchymal stem cells and natural killer cells.Stem Cells,2006,24:74-85.
21张华勇,冯学兵,孙凌云.系统性红斑狼疮患者间质干细胞生物学特性及对造血支持的研究.中华风湿病学杂志,2006,10：331-334.
22 Bernasconi NL, Onai N, Lanzavecchia A. A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells.Blood,2003,101:4500-4504.
23 Jiang XX, Zhang Y, Liu B, et al. Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dentritic cells.Blood,2005,105:4120-4126.
24郭根凯,梁军,侯亚义.系统性红斑狼疮患者骨髓间质干细胞对B淋巴细胞免疫抑制作用的初步研究.中华风湿病学杂志,2007(11)：524-527.
25 Anna C, Federica B, Elisa F, et al. Human mesenchymal stem cells modulate B-cell functions.Blood,2006,107:367-372.
26 Sato Y, Araki H, Kato J, et al. Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood,2005,106:756-763.
27 Zhao LR, Duan WM, Reyes M, et al. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol,2002, 174:11-20.
28 Zhang J, Li Y, Chen J, et al. Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. Exp Neurol,2005,195:16-26.
29 Togel F, Hu Z, Weiss K, et al. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol,2005, 289:F31-F42.
30 Kunter U, Rong S, Djuric Z, et al. Transplanted mesenchymal stem cells accelerate glomerular healing in experimental glomerulonephritis. J Am Soc Nephrol,2006,17:2202-2212.
31 Morton JI, Siegel BV. Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice. Proc Natl Acad Sci USA,1974,71(6):2162-2165.
32 Ikehara S, Good RA, Nakamura T, et al. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA,1985,82(8):2483-2487.
33 Ikehara S, Inaba M, Yasumizu R, et al. Autoimmune diseases as stem cell disorders. Tohoku J Exp Med,1994,173(1):141-155.
34孙凌云.自身免疫病一造血干细胞病.中华风湿病学杂志,2000,4(1)：5-6.
35 Sun L Y, Li H, Liang J, et al. The polarization of T lymphocytes modulated by mesenchymal stem cells in NZB/WF1 and BALB/C mice. Int J Mol Sci,2007,8:455-469.
36 Jabs DA, Burek CL, Hu Q, et al. Anti-CD4 monoclonal antibody therapy suppresses autoimmune disease in MRL/Mp-lpr/lpr mice. Cell Immunol,1992,141:496-507.
37 Tsai CY, Wu TH, Huang SF, et al. Abnormal splenic and thymic IL-4 and TNF-alpha expression in MRL-lpr/lpr mice. Scand J Immunol,1995,41:157-163.
38 Prud'homme GJ, Kono DH, Theofilopoulos AN. Quantitative polymerase chain reaction analysis reveals marked overexpression of interleukin-1 beta, interleukin-1 and interferon-gamma mRNA in the lymph nodes of lupus-prone mice. Mol Immunol,1995,32:495-503.
39 Peng SL, Moslehi J, Craft J. Roles of interferon-gamma and interleukin-4 in murine lupus. J Clin Invest,1997,99:1936-1946.
40 Nicoletti F, Meroni P, Dimarco R, et al. In vivo treatment with a monoclonal antibody to interferongamma neither affects the survival nor the incidence of lupusnephritis in the MRL-lpr/lpr mouse. Immunopharmacology,1992,24:11-16.
41 Shimizu S, Sugiyama N, Masutani K, et al. Membranous glomerulonephritis development with Th2-type immune deviations in MRL/lpr mice deficient for IL-27 receptor (WSX-1). J Immunol,2005, 175:7185-7192.
42 Jabs DA, Lee B, Whittum-Hudson JA, et al. Thl versus Th2 immune responses in autoimmune lacrimal gland disease in MRL/Mp mice. Invest Ophthalmol Vis Sci,2000,41:826-831.
43 Schwarting A, Moore K, Wada T, et al. IFN-gamma limits macrophage expansion in MRL-Fas(lpr) autoimmune interstitial nephritis:a negative regulatory pathway. J Immunol,1998,160:4074-4081.
44张华勇,冯学兵,马晓蕾,等.异基因骨髓间充质干细胞移植治疗系统性红斑狼疮11例临床分析.中华风湿病学杂志,2009,13：89-92.
45 Lazzari L, Lucchi S, Rebulla P, et al. Long-term expansion and maintenance of cord blood haematopoietic stem cells using thrombopoietin, Flt3-ligand, interleukin (IL)-6 and IL-11 in a serum-free and stroma-free culture system. Br J Haematol,2001,112(2):397-404.
46 Biesecker LG, Emerson SG. Interleukin-6 is a component of human umbilical cord serum and stimulates hematopoiesis in embryonic stem cells in vitro. Exp Hematol,1993,21(6):774-778.
47 Armitage RJ, Namen AE, Sassenfeld HM, et al. Regulation of human T cell proliferation by IL-7. J Immunol,1990,144(3):938-941.
48 Fry TJ, Mackall CL. The many faces of IL-7:from lymphopoiesis to peripheral T cell maintenance. J Immunol,2005,174(11):6571-6576.
49 Kurzrock R. Thrombopoietic factors in chronic bone marrow failure states:the platelet problem revisited. Clin Cancer Res,2005,11(4):1361-1367.
50 Minehata K, Mukouyama YS, Sekiguchi T, et al. Macrophage colony stimulating factor modulates the development of hematopoiesis by stimulating the differentiation of endothelial cells in the AGM region. Blood,2002,99(7):2360-2368.
51 Thomas D, Vadas M, Lopez A. Regulation of haematopoiesis by growth factors-emerging insights and therapies. Expert Opin Biol Ther,2004,4(6):869-879.
52 Lyman SD, Jacobsen SE. c-kit ligand and Flt3 ligand:stem/progenitor cell factors with overlapping yet distinct activities. Blood,1998,91(4):1101-1134.
53 Arrighi JF, Hauser C, Chapuis B, et al. Long-term culture of human CD34(+) progenitors with FLT3-ligand, thrombopoietin, and stem cell factor induces extensive amplification of a CD34(-)CD14(-) and a CD34(-)CD14(+) dendritic cell precursor. Blood,1999,93(7):2244-2252.
54 Luens KM, Travis MA, Chen BP, et al. Thrombopoietin, kit ligand, and flk2/flt3 ligand together induce increased numbers of primitive hematopoietic progenitors from human CD34+Thy-1+Lin-cells with preserved ability to engraft SCID-hu bone. Blood,1998,91(4):1206-1215.
55 Gaffney PM, Ortmann WA, Selby SA, et al. Genome screening in human systemic lupus erythematosus:results from a second Minnesota cohort and combined analyses of 187 sib-pair families. Am J Hum Genet.2000,66:547-556.
56 International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley JB, Alarcon-Riquelme ME, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008,40:204-210.
57 Hom G, Graham RR, Modrek B, et al. Association of systemic lupus erythematosus with C8 or f13-BLK and ITGAM-ITGAX. N Engl J Med.2000,358:900-909.
58冯学兵,沈南,陈顺乐,等。中国人群16号染色体q12区存在SLE易感基因。中华医学遗传学杂志2003,20：27-30.
59冯学兵,沈南,罗纬琼,等。系统性红斑狼疮患者16q12精细定位研究。中华风湿病学杂志2004,8：454-457.
60冯学兵,沈南,罗纬琼,等。中国人群系统性红斑狼疮患者OAz基因多态性研究。中华医学遗传学学杂志2004,21：430-434.
61 Gillett CD, Langefeld CD, Williams AH, et al. Fine mapping chromosome 16q12 in a collection of 231 systemic lupus erythematosus sibpair and multiplex families. Genes Immun.2005,6:19-23.
62 Nath SK, Namjou B, Hutchings D, et al. Systemic lupus erythematosus (SLE) and chromosome 16: confirmation of linkage to 16q12-13 and evidence for genetic heterogeneity. Eur J Hum Genet.2004, 12:668-672.
63 Lee YH, Nath SK. Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. Hum Genet.2005,118:434-443.
64 Cantor RM, Yuan J, Napier S, et al. Systemic lupus erythematosus genome scan:support for linkage at 1q23,2q33,16q12-13, and 17q21-23 and novel evidence at 3p24,10q23-24,13q32, and 18q22-23. Arthritis Rheum.200,50:3203-3210.
65 Ath SK, Han S, Kim-Howard X, et al. A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet.2008,40:152-154.
66 Wrana JL. Regulation of Smad activity. Cell,2000,100:189-192.
67 Scott Fields, Kristina Ternyak, Hua Gao, et al. The'zinc knuckle'motif of early B cell factor is required for transcriptional activation of B cell-specific genes. Molecular Immunol,2008,45:3786-3796.
68 Bond HM, Mesuraca M, Carbone E, et al. Early hematopoietic zinc finger protein (EHZF), the human homologue to mouse Evi3, is highly expressed in primitive human hematopoietic cells. Blood,2004, 103:2062-2070.
69 Zon LI. Self-renewal versus differentiation, a job for the mighty morphogens. Nat Immunol 2001, 2:142-143.
70 Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003,425:836-841.
71 Heasley LE, Petersen BE. Signalling in stem cells. EMBO Rep 2004,5:241-244.
72 Manching Ku, Shavonne Howard, Weihua Ni, et al.OAZ regulates bone morphogenetic protein signaling through Smad6 activation. J Biol Chem,2006,281:5277-5287.
73 Davis BN, Hilyard AC, Lagna G, Hata et al. A SMAD proteins control DROSHA-mediated microRNA maturation. Nature,2008,454:56-61.
74 Jonas Larsson, Stefan Karlsson. The role of Smad signaling hematopoiesis. Oncogene,2005, 24:5676-5692.
75 Andreas von Bubnoff, Daniel A. Peiffer, Ira L. Blitz, et al.Phylogenetic footprinting and genome scanning identify vertebrate BMP response elements and new target genes. Developmental Biology, 2005,281:210-226.
76 Christian Kersten, Guri Dosen, June H. Myklebust, et al.BMP-6 inhibits human bone marrow B lymphopoiesisd Upregulation of Id1 and Id3. Exp Hematol,2006,34:72-81.
1 冯学兵,沈南,罗纬琼,等.系统性红斑狼疮患者16q12精细定位研究.中华风湿病学杂志,2004,8：454-457.
2 Bombardier C, Gladman DD, Urowitz MB, et al. Derivation of the SLEDAI:a disease activity index for lupus patients:the committee on prognosis studies in SLE. Arthritis Rheum,1992,35:630-640.
3 Arnett FC, Edworthy SM, Bloch DA, et al.The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum,1988,31:315-324.
4 Feng X, Wu H, Grossman JM, et al. Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheum,2006, 54:2951-62.
5 Pitashny M, Schwartz N, Qing X, et al. Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis. Arthritis Rheum,2007,56:1894-903.
6 Muro Y. Antinuclear antibodies. Autoimmunity,2005,38:3-9.
7 冯学兵,沈南,陈顺乐,等.中国人群16号染色体q12区存在SLE易感基因.中华医学遗传学杂志,2003,20：27-30.
8 冯学兵,沈南,陈顺乐,等.系统性红斑狼疮患者16号染色体候选基因表达研究.中华皮肤科杂志,2003,36：322-324.
9 Liang D, Huang XQ, Shen N, et al. Variations within OLF1/EBF-associated zinc finger protein gene confer susceptibility to lupus nephritis in Chinese population. Zhonghua yi Xue Za Zhi,2005,85:949-54.
10 Wrana JL. Regulation of Smad activity. Cell,2000,100:189-192.
11 Scott Fields, Kristina Ternyak, Hua Gao, et al. The'zinc knuckle'motif of early B cell factor is required for transcriptional activation of B cell-specific genes. Mol Immunol,2008,45:3786-96.
12 Bond HM, Mesuraca M, Carbone E, et al. Early hematopoietic zinc finger protein (EHZF), the human homologue to mouse Evi3, is highly expressed in primitive human hematopoietic cells. Blood,2004,103: 2062-70.
13 Zon LI. Self-renewal versus differentiation, a job for the mighty morphogens. Nat Immunol 2001, 2:142-143.
14 Zhang J, Niu C, Ye L, et al. Identification of the haematopoietic stem cell niche and control of the niche size. Nature 2003,425:836-841.
15 Heasley LE, Petersen BE. Signalling in stem cells:meeting on signal transduction determining the fate of stem cells.EMBO Rep 2004,5:241-244.
16 Manching Ku, Shavonne Howard, Weihua Ni, et al.OAZ regulates bone morphogenetic protein signaling through Smad6 activation. J Biol Chem,2006,281:5277-5287.
17 Davis BN, Hilyard AC, Lagna G, et al. SMAD proteins control DROSHA-mediated microRNA maturation. Nature,2008,454:56-61.
18 Jonas Larsson, Stefan Karlsson. The role of Smad signaling hematopoiesis. Oncogene,2005,24:5676-92.
19 Andreas von Bubnoff, Daniel A. Peiffer, Ira L. Blitz, et al.Phylogenetic footprinting and genome scanning identify vertebrate BMP response elements and new target genes. Dev Biol,2005,281:210-226.
20 Christian Kersten, Guri Dosen, June H. Myklebust, et al.BMP-6 inhibits human bone marrow B lymphopoiesisd Upregulation of Id1 and Id3. Exp Hematol,2006,34:72-81.
1 冯学兵,沈南,罗纬琼,等.系统性红斑狼疮患者16q12精细定位研究.中华风湿病学杂志,2004,8：454-457.
2 Shim S, Bae N, Han JK. Bone morphogenetic protein-4-induced activation of Xretpos is mediated by Smads and Olf-1/EBF associated zinc finger (OAZ). Nucleic Acids Res 2002; 30:3107-3017.
3 李荣良,黄静,孙凌云,等.系统性红斑狼疮OAZ通路基因表达研究.中华医学杂志,2009,89：2068-2071.
4 Bombardier C, Gladman DD, Urowitz MB, et al. Derivation of the SLEDAI:a disease activity index for lupus patients, the committee on prognosis studies in SLE. Arthritis Rheum,1992,35:630-640.
5 Feng X, Wu H, Grossman JM, et al. Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis Rheum,2006, 54:2951-62.
6 冯学兵,沈南,陈顺乐,等.中国人群16号染色体q12区存在SLE易感基因.中华医学遗传学杂志,2003,20：27-30.
7 冯学兵,沈南,陈顺乐,等.系统性红斑狼疮患者16号染色体候选基因表达研究.中华皮肤科杂志,2003,36：322-324.
8 Wrana JL. Regulation of Smad activity. Cell,2000,100:189-192.
9 Benezra R, Davis RL, Lockshon D, et al. The protein Id:a negative regulator of helix-loop-helix DNA binding proteins. Cell,1990,61:49-59.
10 Massari ME, Murre C. Helix-loop-helix proteins:regulators of transcription in eucaryotic organisms. Mol Cell Biol,2000,20:429-440.
11 Rivera R, Murre C. The regulation and function of the Id proteins in lymphocyte development. Oncogene, 2001,20:8308-8316.
12 Mori S, Nishikawa SI, Yokota Y. Lactation defect in mice lacking the helix-loop-helix inhibitor Id2. EMBOJ,2000,19:5772-5781.
13周琳,屠小刚,朱烨,等.系统性红斑狼疮患者血清B淋巴细胞刺激因子水平的检测.中华风湿病杂,2005,9(4)：222-224.
14李慧,梁军,侯亚义,等.NZBWF1/J鼠骨髓间充质干细胞对淋巴细胞亚群平衡的免疫调节.中华风湿病学杂志,2006,10：457-461.
15 Parrish-Novak J, Dillon SR, Nelson A, et al. Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function. Nature,2000,408:57-63.
16 Ozaki K, Spolski R, Ettinger R, et al. Regulation of B cell differentiation and plasma cell generation by IL21, a novel inducer of Blimp-land Bcl-6. J Immunol,2004,173:5361-5371.
17 Ozaki K, Spolski R, Feng CG, et al. A critical role for IL-21 in regulating immunoglobulin production. Science,2002,298:1630-1634.
18 Pene J, Gauchat JF, Lecart S, et al. Cutting edge:IL-21 is a switch factor for the production of IgGl and IgG3 by human B cells. J Immunol,2004,172:5154-5157.
19 Herber D, Brown TP, Liang S. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. J Immunol.2007,178,3822-3830.
20 Rafei M, Hsieh J, Fortier S, et al. Mesenchymal stromal cell_derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction. Blood,2008,112:4991-4998.
1 冯学兵,沈南,罗纬琼,等.系统性红斑狼疮患者16q12精细定位研究.中华风湿病学杂志,2004,8：454-457.
2 Shim S, Bae N, Han JK. Bone morphogenetic protein-4-induced activation of Xretpos is mediated by Smads and Olf-1/EBF associated zinc finger (OAZ). Nucleic Acids Res 2002; 30:3107-3017.
3 李荣良,黄静,孙凌云,等.系统性红斑狼疮OAZ通路基因表达研究.中华医学杂志,2009,89：2068-2071.
4 黄静,李荣良,冯学兵,等.系统性红斑狼疮干扰素诱导基因表达研究.中华内科学杂志,2010,49：45-48.
5 李荣良,黄静,周涛,等.siRNA阻断OAZ信号通路对狼疮抗核抗体产生的影响.中华风湿病学杂志,2010,14：3-7.
6 Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum,1997,40:1725.
7 张华勇,冯学兵,马晓蕾,等.异基因骨髓间充质干细胞移植治疗系统性红斑狼疮11例临床分析.中华风湿病学杂志,2009,13：89-92.
8 Morton JI, Siegel BV. Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice. Proc Natl Acad Sci U S A,1974,71(6):2162-2165.
9 Ikehara S, Good RA, Nakamura T, et al. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA,1985,82(8):2483-2487.
10 Ikehara S, Inaba M, Yasumizu R, et al. Autoimmune diseases as stem cell disorders. Tohoku J Exp Med, 1994,173(1):141-155.
11孙凌云.自身免疫病一造血干细胞病.中华风湿病学杂志,2000,4(1)：5-6.
12 El-Badri NS, Pascual C, Ferrari A, et al. Abnormalities of stromal cells in autoimmune systemic lupus murine model. Blood,2004,104:364A.
13顾志峰,赵盛楠,张华勇,等.系统性红斑狼疮患者骨髓MSC超微结构及细胞骨架特征.中华风湿病学杂志,2008,12：397-400.
14 Sun LY, Zhang HY, Feng XB, et al. Abnormality of bone marrow-derived stem cell in patients with systemic lupus erythematosus. Lupus.2007,16:121-128.
15 Sun L Y, Li H, Liang J, et al. The polarization of T lymphocytes modulated by mesenchymal stem cells in NZB/WF1 and BALB/C mice. Int J Mol Sci,2007,8:455-469.
16 Wrana JL. Regulation of Smad activity. Cell,2000,100:189-192.
17 Benezra R, Davis RL, Lockshon D, et al. The protein Id:a negative regulator of helix-loop-helix DNA binding proteins. Cell,1990,61:49-59.
18 Massari ME, Murre C. Helix-loop-helix proteins:regulators of transcription in eucaryotic organisms. Mol Cell Biol,2000,20:429-440.
19 Rivera R, Murre C. The regulation and function of the Id proteins in lymphocyte development. Oncogene, 2001,20:8308-8316.
20 Mori S, Nishikawa SI, Yokota Y. Lactation defect in mice lacking the helix-loop-helix inhibitor Id2. EMBO J,2000,19:5772-5781.
21汤建平,顾越英,沈南,等.干扰素诱导表达的淋巴细胞抗原6复合体E和干扰素诱导蛋白1基因与系统性红斑狼疮患者病情活动性的关系.中华医学杂志,2004,84：1157-1160.
22 Herber D, Brown TP, Liang S. IL-21 has a pathogenic role in a lupus-prone mouse model and its blockade with IL-21R.Fc reduces disease progression. J Immunol.2007,178,3822-3830.
23李慧,梁军,侯亚义,等.NZBWF1/J鼠骨髓间充质干细胞对淋巴细胞亚群平衡的免疫调节.中华风湿病学杂志,2006,10：457-461.
24 Rafei M, Hsieh J, Fortier S, et al. Mesenchymal stromal cell derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction. Blood,2008,112:4991-4998.
1 Hofman RW. T cells in the pathogenesis of systemic lupus erythematosus. Clin Immunol,2004,113:4-13.
2 栾希英,张光波,胡玉敏,等.人骨髓MSC对PHA活化T细胞周期以及表型和细胞因子分泌的影响.细胞与分子免疫学杂志,2007,23：402-405.
3 Groh ME, Maitra B, Szekely E, et al. Human mesenchymal stem cells require monocyte-mediated activation to suppress alloreactive T cells. Exp Hematol,2005,33:928-934.
4 李慧,梁军,孙凌云,等.NZBWF1/J鼠骨髓间充质干细胞对T淋巴细胞亚群平衡的免疫调节.中华风湿病学杂志,2006,10：457-461.
5 Rasmusson I, Ringden O, Sundberg B, et al. Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms. Exp Cell Res,2005,305:33-41.
6 Sbano P, Cuccia A, Mazzanti B, et al.Use of donor bone marrow mesenchymal stem cells for treatment of skin allograft rejection in a preclinical rat model. Arch Dermatol Res,2008,300:115-24.
7 Plumas J, Chaperot L, Richard MJ, et a 1. Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia,2005,19:1597-1604.
8 Djouad F, Plence P, Bony C, et al.Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood,2003,102:3837-3844.
9 Krampers M, Glennie S, Dyson J, et al. Bone marrow mesenchymal stem cells inhibit the response of native and memory antigen specific T cells to their congnate peptide. Blood,2003,101:3722-3729.
10 Di Nicola M, Carlo Stella C, Magni M, et al. Human bone marrow stromal cells suppress T lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood,2002,99:3838-3843.
11 Zappia E, Casazza S, Pedemonte E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T cell anergy. Blood,2005,106:1755-1761.
12 Chabannes D, Hill M, Merieau E, et al. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood,2007,110:3691-3694.
13 Krampera M, Cosmi L, Angeli R, et al. Role of the IFN-y in the immunomodulatory activity of human mesenchymal stem cells. Stem cells,2005,24:386-398.
14 Sotiropoulou PA, Perez SA, Gritzapis AD, et al. Interactions between human mensenchymal stem cells and natural killer cells. Stem Cells,2006,24:74-85.
15张伟,葛薇,李长红,等.骨髓间充质干细胞通过上调CD8+ CD28T细胞抑制T细胞的增殖.中国实验血液学杂志,2004,12：666-669.
16 Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood,2005,105:1815-1822.
17孙凌云,顾宁琰,侯亚义,等.系统性红斑狼疮骨髓间质干细胞的初步研究.中华风湿病学杂志,2005,9：586-589.
18 Papadaki HA, Boumpas DT, Gibson FM, et al. Increased apoptosis of bone marrow CD34+ cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus. Br J Haematol,2001,115:167-174.
19 El-Badri NS, Pascual C, Ferrari A, et al. Abnormalities of stromal cells in autoimmune systemic lupus murine model. Blood,2004,104:364A.
20顾志峰,赵盛楠,张华勇,等.系统性红斑狼疮患者骨髓MSC超微结构及细胞骨架特征.中华风湿病学杂志,2008,12：397-400.
21李慧,孙凌云.MRL/lpr鼠骨髓间充质干细胞对T淋巴细胞作用的研究.中华风湿病学杂志,2007,11：340-343.
22 Lee JH, Wang LC, Lin YT, et al. Inverse correlation between CD4 regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus. Immunol,2006,117: 280-286.
23 Miyara M, Amoura Z, Parizot C, et al. Global natural regulatory T cell depletion in active systemic lupus erythematosus. J Immunol,2005,175:8392-8400.
24 Filaci G, Bacilieri S, Fravega M, et al. Impairment of CD8+ T suppressor cell function in patients with active systemic lupus erythematosus. J Immnol,2001,166:6452-6457.
25 Funauchi M, Sugiyama M, Sukyoo B, et al. A possible role of apoptosis for regulating autoreactive responses in systemic lupus erythematosus. Lupus,2001,10:284-288.
26顾志峰,金欧阳,徐婷,等.脐带间质干细胞移植治疗狼疮鼠的疗效.中华风湿病学杂志,2009,13：4-7.
27 Zhou K, Zhang H, Jin O, Feng X, Yao G, Hou Y, Sun L. Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice. Cell Mol Immunol, 2008,5:417-424.
28 Sun L Y, Li H, Liang J, et al. The polarization of T lymphocytes modulated by mesenchymal stem cells in NZB/WF1 and BALB/C mice. Int J Mol Sci,2007,8:455-469.
29赵盛楠,张华勇,顾志峰,等.间充质干细胞对系统性红斑狼疮CD4+ Foxp3+ T淋巴细胞的调节.中华风湿病学杂志,2008,12：7-10.
30孙凌云,张华勇,冯学兵,等.异基因骨髓间质干细胞移植治疗难治性红斑狼疮.实用临床医药杂志,2007,11：2-4.
[1]Sun L Y, Zhang H Y, Fen X B, et al. Abnormality of bone marrow-derived stem cell in patients with systemic lupus erythematosus. Lupus,2007,16(2):121.
[2]Remer CF, Weisman MH, Wallace DJ. Benefits of leflunomide in systemic lupus erythematosus:a pilot observational study. Lupus,2001,10:480-3.
[3]Mok CC, Tong KH, To CH, et al. Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: an open-labeled pilot study. Kidney Int,2005,68:813-7.
[4]Chan TM, Li FK, Tang CS, et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong-Guangzhou Nephrology Study Group. N Engl J Med,2000,343:1156-62.
[5]Hu W, Liu Z, Chen H, et al. Mycophenolate mofetil vs cyclophosphamide therapy for patients with diffuse proliferative lupus nephritis. Chin Med J (Engl),2002,115:705-9.
[6]Alarcon-Segovia D, Tumlin JA, Furie RA, et al. LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus:results from a randomized, double-blind, placebo-controlled study. Arthritis Rheum,2003,48:442-54.
[7]Sfikakis PP, Boletis JN, Lionaki S, et al. Remission of proliferative lupus nephritis following B cell depletion therapy is preceded by down-regulation of the T cell costimulatory molecule CD40 ligand:an open-label trial. Arthritis Rheum,2005,52:501-13.
[8]Seshasayee D, Valdez P, Yan M, et al. Loss of TACI causes fatal lymphoproliferation and autoimmunity, establishing TACI as an inhibitory BLyS receptor. Immunity,2003,18:279-88.
[9]Boumpas DT, Furie R, Manzi S, et al. A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Arthritis Rheum,2003,48:719-27.
[10]Kalunian KC, Davis JC Jr, Merrill JT, et al. Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD 154:a randomized, double-blind, placebo-controlled trial. Arthritis Rheum,2002,46:3251-8.
[11]Larsen CP, Pearson TC, Adams AB, et al. Rational development of LEA29Y (belatacept), a high-affinity variant of CTLA4-Ig with potent immunosuppressive properties. Am J Transplant,2005,5:443-53.
[12]Daikh DI, Wofsy D. Cutting edge:reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide. J Immunol,2001,166:2913-6.
[13]Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science,1999,284(5411):143-147.
[14]Koc ON, Gerson SL, Cooper BW, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol,2000,18(2):307-316.
[15]Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood,2002,99(10):3838-3843.
[16]Tse WT, Pendleton JD, Beyer WM, et al. Suppression of allogeneic T-cell proliferation by human marrow stromal cells:implications in transplantation. Transplantation,2003,75(3):389-397.
[17]Le Blanc K, Tammik L, Sundberg B, et al. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol,2003,57(1):11-20.
[18]Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals.Blood,2003,102(10):3837-3844.
[19]Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol,2002,30(1):42-48.
[20]Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet,2004,363(9419):1439-1441.
[21]Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol,2003,31(10):890-896.
[22]Morton JI, Siegel BV. Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice. Proc Natl Acad Sci USA,1974,71(6):2162-2165.
[23]Ikehara S, Good RA, Nakamura T, et al. Rationale for bone marrow transplantation in the treatment of autoimmune diseases. Proc Natl Acad Sci USA,1985,82(8):2483-2487.
[24]Papadaki HA, Boumpas DT, Gibson FM, et al. Increased apoptosis of bone marrow CD34(+) cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus. Br J Haematol,2001,115(1):167-174.
[25]Ikehara S. New strategies for allogeneic BMT. Bone Marrow Transplant,2003,32 Suppl 1:S73-75.
[26]李慧,孙凌云.间质干细胞的免疫调节及免疫治疗作用研究.中华医学杂志,2006,86：501.
[27]Sun L Y, Li H, Liang J, et al, The polarization of T lymphocytes modulated by mesenchymal stem cells in NZB/WF1 and BALB/C mice. Int JMol Sci,2007,8:455.
[28]Ikehara S. New strategies for allogeneic BMT, Bone Marrow Transplant,2003,32:S73.
[29]孙凌云,张华勇,冯学兵,等.异基因骨髓间质干细胞移植治疗难治性红斑狼疮.实用临床医药杂志,2007,11(4)：2-4.
[30]董燕湘,董晓先,何慧华,等.大鼠骨髓间质干细胞用中药绞股蓝诱导为神经细胞的研究[J].中华神经科杂志,2003,36(5)：355.
[31]张进,徐志伟.补肾法诱导间充质干细胞向神经方向分化研究[J].现代医院,2004,4(9)：15.
[32]苏平,黄建华,雒晓东,等.银杏内酯B对骨髓间充质干细胞分化为神经样细胞的影响.广东医学,2007,28(1)：33-35.
[33]冼绍祥, 杨忠奇, 汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究.广州中医药大学学报,2007,24(1)：37-40.
[34]史风雷,李刚,王海彬,等.袁氏生脉成骨胶囊对激素诱导骨髓基质细胞成脂分化的拮抗作用[J].广州中医药大学学报,2003,20(4)：302.
[35]杨博华,秦建辉,朱龄群,等.自体骨髓干细胞移植合中药治疗下肢动脉缺血[J].浙江中西医结合杂志,2004,14(11)：683.
[1]Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science,1999,284(5411):143-147.
[2]贾正平,张汝学,等.淫羊藿总黄酮含药血清促进骨髓间充质干细胞增殖与成骨性分化.中国骨质疏松杂志,2004,10(4)：420-422.
[3]肖鲁伟,武中庆,季卫锋,等.右归饮诱导胎兔骨髓基质细胞向软骨细胞分化的实验研究.中国中医药科技,2005,12(3)：154.
[4]张进,徐志伟.补肾法诱导间充质干细胞向神经方向分化研究.现代医院,2004,4(9)：15.
[5]冼绍祥,杨忠奇,汪朝晖,等.黄芪甲苷体外诱导骨髓间充质干细胞分化为心肌样细胞的实验研究.广州中医药大学学报,2007,24(1)：37-40.
[6]Majumdar MK, Thiede MA, Mosca JD, et al. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSC) and stromal cells. J Cell Physiol,1998,176(1):57-66.
[7]Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol,1999,181(1):67-73.
[8]Koc ON, Gerson SL, Cooper BW, et al. Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol,2000,18(2):307-316.
[9]张新华,黄有文,王荣新,等.益髓生血灵对小鼠骨髓造血干／祖细胞的影响.浙江中医杂志,2002,37(10)：448.
[10]陈志雄,曹克俭,薛恺睿,等.活髓片对环磷酰胺造模小鼠骨髓骨髓细胞DNA含量及细胞周期的影响.中医杂志,1999,40(11)：686.
[11]梁毅,陈志雄,丘和明,等.活髓片与四物汤对免疫介导再障小鼠骨髓基质细胞的影响比较.中国中西医结合急救杂志,2002,9(6)：327.
[12]Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood,2002,99(10):3838-3843.
[13]Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol,2002,30(1):42-48.
[14]Le Blanc K, Rasmusson I, Sundberg B, et al. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet,2004,363(9419):1439-1441.
[15]Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol,2003,31(10):890-896.
[16]杨博华,秦建辉,朱龄群,等.自体骨髓干细胞移植合中药治疗下肢动脉缺血.浙江中西医结合杂志,2004,14(11)：683.