脂肪间充质干细胞修复放射性肠损伤的实验研究
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摘要
目的：本研究旨在利用脂肪来源的间充质干细胞（Ad-MSC），评价其对放射性肠损伤的修复作用。
方法：本研究采用的实验动物为成年雄性SD大鼠，SPF级，体重400~450g，共152只。首先，选择其中36只大鼠进行放射性肠损伤的剂量效应关系研究。将其平均分为4组，每组9只。分别给予0、8.5、12及15Gy的全腹部X射线照射。照射后14d内，每2d称量大鼠体重，计算占初始体重的百分比；记录受照大鼠的腹泻发生率及便潜血阳性率；H&E染色分析受照小肠组织形态的变化；采用One-way ANOVA方法对组间数据进行比较。然后，选择40只大鼠进行了Ad-MSC修复放射性肠上皮损伤的实验研究。将大鼠分为3组：健康对照组（6只）、PBS溶剂对照组（17只）和Ad-MSC治疗组（17只）。全腹照射剂量为15Gy，腹腔移植的Ad-MSC数量为5×106/只。PBS腹腔注射量为：1.5ml/只。在照射后的第10、20及30d，将PBS溶剂对照组及Ad-MSC治疗组的大鼠分批处死，每组3只。获取新鲜的肠组织标本进行上皮完整性的分析，包括：H&E染色分析受照肠组织形态，Ki67免疫组化染色分析隐窝细胞增殖，TUNEL检测受照肠组织凋亡细胞，Bmi1免疫组化染色分析隐窝Bmi1阳性肠干细胞数量，实时荧光定量PCR检测受照组织内EGF、KGF、E-Cadherin、Bax和Bcl-2基因的表达。统计分析各组大鼠体重变化及生存率。然后，再次选择40只大鼠，采用同样的分组方法和造模方法进行了Ad-MSC修复损伤血管的实验研究。在照射后的第10、20及30d，将PBS溶剂对照组及Ad-MSC治疗组的大鼠分批处死，每组3只。免疫荧光染色分析受照部位CD31/vWF双阳性血管内皮细胞的数量，Isolectin-B4染色分析受照部位脉管系统的密度，VE-Cadherin免疫组化染色分析受照部位血管结构的完整性。CD31/CD105/CD34/CD45/CD133/Ki67免疫荧光染色分析受照部位血管的新生机制，实时荧光定量PCR检测受照组织内VEGF、HGF和SDF-1因子的表达量。统计分析各组大鼠的体重及生存率变化。最后选取剩余36只大鼠，进行了Ad-MSC的抗炎作用研究。实验分为3组：健康对照组（6只）、PBS溶剂对照组（15只）和Ad-MSC治疗组（15只）。造模方法同前。在照射后第3.5、7、10、20和30d，将PBS溶剂对照组和Ad-MSC治疗组大鼠分批处死，每组3只。获取大鼠外周血及胸腺组织。流式细胞术分析样本中CD4/CD25/Foxp(3)阳性调节性T细胞的百分比。ELISA方法检测外周血IL-10的含量。获取受损肠组织，Masson染色分析受照肠组织胶原的沉积，MPO免疫组化染色分析炎症细胞在损伤部位的浸润。PBS溶剂对照组及Ad-MSC治疗组数据采用配对t检验来进行比较。
结果：研究发现，放射性肠损伤的损伤程度与辐射剂量具有线性依赖关系。以15Gy剂量引起的病理变化具有典型的放射性肠损伤疾病特征。与PBS溶剂对照组相比，Ad-MSC能够上调损伤部位EGF、KGF和Bcl-2基因的表达，促进隐窝细胞的增殖；通过下调损伤部位Bax基因的表达，抑制上皮细胞的凋亡。从而增加了隐窝内Bmi1阳性肠干细胞的数量。另外，Ad-MSC通过上调损伤部位VEGF、HGF和SDF-1基因的表达动员骨髓中CD31阳性造血干/祖细胞向损伤部位迁移，促进该部位血管的重建。不仅如此，Ad-MSC能够上调外周血及胸腺组织内的CD4/CD25/Foxp(3)炎性调节性T细胞的百分比，提高外周血中IL-10的含量，减轻受照大鼠体内的炎症反应。
结论：Ad-MSC对放射性肠损伤具有修复作用，这是通过促进上皮完整性恢复、加速受损部位血管结构的重建以及减轻宿主体内炎症反应3方面来完成的。
Objective: To assess the therapeutic effects of adipose-derivedmesenchymal stem cells (Ad-MSC) on radiation-induced intestinalinjury.
Method: A total of152male Sprague-Dawley rats, weighting400~450g, were enrolled in this study. Firstly,36rats were selected forevaluating the relationship between the ionizing doses and tissue damage.The rats were classified into four groups. Each group contained9rats.They were respectively irradiated with0,8.5,12and15grays (Gy) totheir whole abdomens. During a period of14days after irradiation, allrats were weighted every other day, and the incidences of diarrhea andoccult blood were recorded. Besides, the histological changes wereanalyzed using H&E staining. The data from the four groups werecompared using One-way ANOVA method. After that, we selected40rats to evaluate the effect of Ad-MSC on maintaining the integrity ofintestinal epithelium after irradiation. Herein,34rats, receiving15Gyionizing irradiation, were used for establishing models ofradiation-induced intestinal injury. Thereafter,17rats were respectivelyadministrated with a dose of5×106cells intrapersonally (Ad-MSCgroup). Another17rats were respectively injected with1.5ml phosphate buffered saline (PBS group). The remaining6rats were used as thecontrols (Normal group). At10,20and30days post-irradiation, theinjured tissue was freshly isolated for analyzing the integrity of intestinalepithelium, including their morphology using H&E staining,proliferative cells and intestinal stem cells within crypts using eitherKi67or Bmi1IHC-staining. TUNEL for apoptotic cells and thegene-profiles containing EGF, KGF, E-Cadherin, Bcl-2and Bax usingReal-time PCR. Besides, the survival of rats and their body-weightvariation were also recored. Next, another40rats were used in the studyof Ad-MSC promoting micro-vascular reconstruction within injuredintestine. The approaches of grouping and modeling were as same asthose in previous study. A t10,20and30days post-irradiation, each3rats from either the PBS group or the Ad-MSC group were sacrificed.The samples were used for identifying the CD31and vWFdouble-positive cells in the injured tissues by IF-staining. In addition,the integrity of vasculature was analyzed by VE-Cadherin IHC-staining,and the density of micro-blood vessels was tested using Isolectin-B4.Markers including CD31, CD34, CD45, CD105, CD133and Ki67wereused for analyzing the mobilized HSC or HPC within injured tissue.Besides, the expressions of VEGF, HGF and SDF-1in irradiatedintestine were also tested using real-time PCR. Lastly, the remaining36rats were used for analyzing the anti-inflammatory effect of Ad-MSC. There were6,15and15rats in the normal, PBS and Ad-MSC groups,respectively. At3.5,7,10,20and30days post-irradiation, each3ratsfrom either the PBS group or the Ad-MSC group were sacrificed. Theperipheral blood and thymus were harvested for computing thepercentages of CD4/CD25/Foxp(3) triple-positive regulatory T cells.Besides, levels of IL-10in serum were tested using ELISA method. Thedeposition of collagen was detected by using Masson staining.IHC-staining for MPO was used for identifying the infiltration ofinflammatory cells within injured tissues. The data from the PBS andAd-MSC groups were compared using Paired t-test.
Result: We observed that the degrees of tissue damage depended on theionizing doses, and there were the typical lesions of radiation-inducedintestinal injury in the rats receiving15Gy irradiation. As comparedwith the PBS group, Ad-MSC could promote the proliferation of cellswithin crypts and increase the the number of Bmi1-positve intestinalstem cells through the high expressions of EGF and KGF. Besides, theup-regulated expression of Bcl-2and down-regulated expression of Baxin the Ad-MSC group inhibited the apoptosis of epithelial cells. Theresults also showed that Ad-MSC could promote the neovascularizationin the damaged intestine by triggering mobilization of HSC and HPCtogether with up-regulated expressions of VEGF, HGF and SDF-1.Additionally, after delivery of Ad-MSC, the percentages of CD4/CD25/Foxp(3) triple-positive regulatory T cells increased in boththymus and peripheral blood, which resulted in a high serum level ofIL-10facilitating inflammation in injured tissues.
Conclusion: Ad-MSC had the healing roles on radiation-inducedintestinal injury, representing by the restoring the integrity of epithelium,promoting neovascularization within injured tissues and mitigating theinflammation. Consequently, Ad-MSC had the potentials formanagement of radiation-induced intestinal injury.
方法：本研究采用的实验动物为成年雄性SD大鼠，SPF级，体重400~450g，共152只。首先，选择其中36只大鼠进行放射性肠损伤的剂量效应关系研究。将其平均分为4组，每组9只。分别给予0、8.5、12及15Gy的全腹部X射线照射。照射后14d内，每2d称量大鼠体重，计算占初始体重的百分比；记录受照大鼠的腹泻发生率及便潜血阳性率；H&E染色分析受照小肠组织形态的变化；采用One-way ANOVA方法对组间数据进行比较。然后，选择40只大鼠进行了Ad-MSC修复放射性肠上皮损伤的实验研究。将大鼠分为3组：健康对照组（6只）、PBS溶剂对照组（17只）和Ad-MSC治疗组（17只）。全腹照射剂量为15Gy，腹腔移植的Ad-MSC数量为5×106/只。PBS腹腔注射量为：1.5ml/只。在照射后的第10、20及30d，将PBS溶剂对照组及Ad-MSC治疗组的大鼠分批处死，每组3只。获取新鲜的肠组织标本进行上皮完整性的分析，包括：H&E染色分析受照肠组织形态，Ki67免疫组化染色分析隐窝细胞增殖，TUNEL检测受照肠组织凋亡细胞，Bmi1免疫组化染色分析隐窝Bmi1阳性肠干细胞数量，实时荧光定量PCR检测受照组织内EGF、KGF、E-Cadherin、Bax和Bcl-2基因的表达。统计分析各组大鼠体重变化及生存率。然后，再次选择40只大鼠，采用同样的分组方法和造模方法进行了Ad-MSC修复损伤血管的实验研究。在照射后的第10、20及30d，将PBS溶剂对照组及Ad-MSC治疗组的大鼠分批处死，每组3只。免疫荧光染色分析受照部位CD31/vWF双阳性血管内皮细胞的数量，Isolectin-B4染色分析受照部位脉管系统的密度，VE-Cadherin免疫组化染色分析受照部位血管结构的完整性。CD31/CD105/CD34/CD45/CD133/Ki67免疫荧光染色分析受照部位血管的新生机制，实时荧光定量PCR检测受照组织内VEGF、HGF和SDF-1因子的表达量。统计分析各组大鼠的体重及生存率变化。最后选取剩余36只大鼠，进行了Ad-MSC的抗炎作用研究。实验分为3组：健康对照组（6只）、PBS溶剂对照组（15只）和Ad-MSC治疗组（15只）。造模方法同前。在照射后第3.5、7、10、20和30d，将PBS溶剂对照组和Ad-MSC治疗组大鼠分批处死，每组3只。获取大鼠外周血及胸腺组织。流式细胞术分析样本中CD4/CD25/Foxp(3)阳性调节性T细胞的百分比。ELISA方法检测外周血IL-10的含量。获取受损肠组织，Masson染色分析受照肠组织胶原的沉积，MPO免疫组化染色分析炎症细胞在损伤部位的浸润。PBS溶剂对照组及Ad-MSC治疗组数据采用配对t检验来进行比较。
结果：研究发现，放射性肠损伤的损伤程度与辐射剂量具有线性依赖关系。以15Gy剂量引起的病理变化具有典型的放射性肠损伤疾病特征。与PBS溶剂对照组相比，Ad-MSC能够上调损伤部位EGF、KGF和Bcl-2基因的表达，促进隐窝细胞的增殖；通过下调损伤部位Bax基因的表达，抑制上皮细胞的凋亡。从而增加了隐窝内Bmi1阳性肠干细胞的数量。另外，Ad-MSC通过上调损伤部位VEGF、HGF和SDF-1基因的表达动员骨髓中CD31阳性造血干/祖细胞向损伤部位迁移，促进该部位血管的重建。不仅如此，Ad-MSC能够上调外周血及胸腺组织内的CD4/CD25/Foxp(3)炎性调节性T细胞的百分比，提高外周血中IL-10的含量，减轻受照大鼠体内的炎症反应。
结论：Ad-MSC对放射性肠损伤具有修复作用，这是通过促进上皮完整性恢复、加速受损部位血管结构的重建以及减轻宿主体内炎症反应3方面来完成的。
Objective: To assess the therapeutic effects of adipose-derivedmesenchymal stem cells (Ad-MSC) on radiation-induced intestinalinjury.
Method: A total of152male Sprague-Dawley rats, weighting400~450g, were enrolled in this study. Firstly,36rats were selected forevaluating the relationship between the ionizing doses and tissue damage.The rats were classified into four groups. Each group contained9rats.They were respectively irradiated with0,8.5,12and15grays (Gy) totheir whole abdomens. During a period of14days after irradiation, allrats were weighted every other day, and the incidences of diarrhea andoccult blood were recorded. Besides, the histological changes wereanalyzed using H&E staining. The data from the four groups werecompared using One-way ANOVA method. After that, we selected40rats to evaluate the effect of Ad-MSC on maintaining the integrity ofintestinal epithelium after irradiation. Herein,34rats, receiving15Gyionizing irradiation, were used for establishing models ofradiation-induced intestinal injury. Thereafter,17rats were respectivelyadministrated with a dose of5×106cells intrapersonally (Ad-MSCgroup). Another17rats were respectively injected with1.5ml phosphate buffered saline (PBS group). The remaining6rats were used as thecontrols (Normal group). At10,20and30days post-irradiation, theinjured tissue was freshly isolated for analyzing the integrity of intestinalepithelium, including their morphology using H&E staining,proliferative cells and intestinal stem cells within crypts using eitherKi67or Bmi1IHC-staining. TUNEL for apoptotic cells and thegene-profiles containing EGF, KGF, E-Cadherin, Bcl-2and Bax usingReal-time PCR. Besides, the survival of rats and their body-weightvariation were also recored. Next, another40rats were used in the studyof Ad-MSC promoting micro-vascular reconstruction within injuredintestine. The approaches of grouping and modeling were as same asthose in previous study. A t10,20and30days post-irradiation, each3rats from either the PBS group or the Ad-MSC group were sacrificed.The samples were used for identifying the CD31and vWFdouble-positive cells in the injured tissues by IF-staining. In addition,the integrity of vasculature was analyzed by VE-Cadherin IHC-staining,and the density of micro-blood vessels was tested using Isolectin-B4.Markers including CD31, CD34, CD45, CD105, CD133and Ki67wereused for analyzing the mobilized HSC or HPC within injured tissue.Besides, the expressions of VEGF, HGF and SDF-1in irradiatedintestine were also tested using real-time PCR. Lastly, the remaining36rats were used for analyzing the anti-inflammatory effect of Ad-MSC. There were6,15and15rats in the normal, PBS and Ad-MSC groups,respectively. At3.5,7,10,20and30days post-irradiation, each3ratsfrom either the PBS group or the Ad-MSC group were sacrificed. Theperipheral blood and thymus were harvested for computing thepercentages of CD4/CD25/Foxp(3) triple-positive regulatory T cells.Besides, levels of IL-10in serum were tested using ELISA method. Thedeposition of collagen was detected by using Masson staining.IHC-staining for MPO was used for identifying the infiltration ofinflammatory cells within injured tissues. The data from the PBS andAd-MSC groups were compared using Paired t-test.
Result: We observed that the degrees of tissue damage depended on theionizing doses, and there were the typical lesions of radiation-inducedintestinal injury in the rats receiving15Gy irradiation. As comparedwith the PBS group, Ad-MSC could promote the proliferation of cellswithin crypts and increase the the number of Bmi1-positve intestinalstem cells through the high expressions of EGF and KGF. Besides, theup-regulated expression of Bcl-2and down-regulated expression of Baxin the Ad-MSC group inhibited the apoptosis of epithelial cells. Theresults also showed that Ad-MSC could promote the neovascularizationin the damaged intestine by triggering mobilization of HSC and HPCtogether with up-regulated expressions of VEGF, HGF and SDF-1.Additionally, after delivery of Ad-MSC, the percentages of CD4/CD25/Foxp(3) triple-positive regulatory T cells increased in boththymus and peripheral blood, which resulted in a high serum level ofIL-10facilitating inflammation in injured tissues.
Conclusion: Ad-MSC had the healing roles on radiation-inducedintestinal injury, representing by the restoring the integrity of epithelium,promoting neovascularization within injured tissues and mitigating theinflammation. Consequently, Ad-MSC had the potentials formanagement of radiation-induced intestinal injury.
引文
[1]李荣富.放射性肠炎发生机制的研究进展[J].医学综述,2011,17(2):257-259.
[2]闵锐,李雨,潘真.辐射损伤的分类及诊断—介绍美国国家战略储备辐射工作组关于急性放射病治疗的建议之一[J].国外医学（放射医学核医学分册）,2005,29(4):179-185.
[3] Kennedy GD, Heise CP. Radiation colitis and proctitis [J]. ClinColon Rectal Surg,2007,20(1):64-72.
[4]刘国辉,康新,陈功,等.肠内营养对放射性肠炎患者肠屏障功能及机体免疫反应的影响[J].中华放射医学与防护杂志,2012,32(6):612-615.
[5]曾昭冲.腹盆部肿瘤放射治疗学[M].复旦大学出版社,2007:589.
[6] Langberg CW, Sauer T, Reitan JB, et al. Relationship betweenintestinal fibrosis and histopathologic and morphometricchanges in consequential and late radiation enteropathy [J].Acta Oncol,1996,35(1):81-87.
[7] Umar S. Intestinal stem cells [J]. Current gastroenterologyreports,2010,12(5):340-348.
[8] Barker N, van Es JH, Kuipers J, et al. Identification of stemcells in small intestine and colon by marker gene Lgr5[J].Nature,2007,449(7165):1003-1007.
[9] Potten CS. Stem cells in gastrointestinal epithelium: numbers,characteristics and death [J]. Philos Trans R Soc Lond B BiolSci,1998,353(1370):821-830.
[10] Sato T, Vries RG, Snippert HJ, et al. Single Lgr5stem cellsbuild crypt-villus structures in vitro without a mesenchymalniche [J]. Nature,2009,459(7244):262-265.
[11] Clevers H. Stem Cells: A unifying theory for the crypt [J].Nature,2013,495(7439):53-54.
[12] Sato T, Clevers H. Growing self-organizing mini-guts from asingle intestinal stem cell: mechanism and applications [J].Science,2013,340(6137):1190-1194.
[13] Sato T, van Es JH, Snippert HJ, et al. Paneth cells constitutethe niche for Lgr5stem cells in intestinal crypts [J]. Nature,2011,469(7330):415-418.
[14] Schepers AG, Vries R, van den Born M, et al. Lgr5intestinalstem cells havehigh telomerase activity and randomly segregatetheir chromosomes [J]. EMBO J,2011,30(6):1104-1109.
[15] Foltankova V, Legartova S, Kozubek S, et al. DNA-damageresponse in chromatin of ribosomal genes and the surroundinggenome [J]. Gene,2013,522(2):156-167.
[16] Ishizuka S, Martin K, Booth C, et al. Poly (ADP-ribose)polymerase-1is a survival factor for radiation-exposedintestinal epithelial stem cells in vivo [J]. Nucleic Acids Res,2003,31(21):6198-205.
[17] Yan KS, Chia LA, Li X, et al. The intestinal stem cell markersBmi1and Lgr5identify two functionally distinct population [J].Proc Natl Acad Sci USA,2012,109(2):81-87.
[18]王守安,张胜昌,田国忠,等.成人和胎儿回肠器官内微血管构筑[J].解剖学进展,2010,16(5):463-466.
[19] Paris F, Fuks Z, Kang A, et al. Endothelial apoptosis as theprimary lesion initiating intestinal radiation damage in mice [J].Science,2001,293(5528):293-297.
[20] Giblin JP, Hewlett LJ, Hannah MJ. Basal secretion of vonWillebrand factor from human endothelial cells [J]. Blood,2008,112(4):957-964.
[21] Wang J, Boerma M, Fu Q, et al. Significance of endothelialdysfunction in the pathogenesis of early and delayed radiationenteropathy [J]. World J Gastroenterol,2007,13(22):3047-3055.
[22] Hendry JH, Booth C, Potten CS. Endothelial cells and radiationgastrointestinal syndrome [J]. Science,2001,294(5546):1411.
[23] Rao RM, Yang L, Garcia-Cardena G, et al.Endothelial-dependent mechanism of leukocyte recruitment tovascular wall [J]. Cire Res,2007,101(3):234-47.
[24] Auletta JJ, Deans RJ, Bartholomew AM. Emerging roles formultipotent, bone marrow-derived stromal cells in host defense[J]. Blood,2012,119(8):1801-1809.
[25]毕迎惠,韩俊庆,盛巍,等.爱维治对急性放射性肠炎大鼠肠道修复作用的实验研究[J].山东大学学报（医学版）,2007,45(3):274-278.
[26]姜新,辛颖,刘野,等.爱维治保留灌肠在盆腔精确放射治疗中对直肠损伤的保护作用[J].中国老年学杂志,2013,33(18):4392-4394.
[27]叶霈智.放射性肠炎临床治疗现状评述[J].癌症进展,2010,8(1):49-52.
[28] Kountouras J, Zavos C. Recent advances in the management ofradiation colitis [J]. World Gastroenterol,2008,14(48):7289-7301.
[29]周岩冰,李世宽,张建立,等.严重放射性肠损伤28例的综合治疗[J].中华普通外科杂志,2002,17(2):719-720.
[30] Oh H, Seong J, Kim W, et al. Recombinant human epidermalgrowth factor (rh EGF) protects radiation-induced intestinalinjury in murine [J]. J Radiat Res,2010,51(5):535-541
[31] Tessner TG, Muhale F, Riehl TE, et al. Prostaglandin E2reduces radiation-induced epithelial apoptosis though amechanism involving AKT activation and bax translocation [J].J Clin Invest,2004,114(11):1676-85.
[32]王瑞娟,彭瑞云,高亚兵,等. IL-11保护中子照射后肠上皮损伤的Jak/STAT信号转导机制研究[J].细胞与分子免疫学杂志,2009,25(1):27-30.
[33] Cai Y, Wang W, Liang H, et al. Keratinocyte growth factorpretreatment prevents radiation-induced intestinal damage in amouse model [J]. Scand J Gastroenterol,2013,48(4):419-426.
[34] Liu Y, Kudo K, Abe Y, et al. Inhibition of transforming growthfactor-beta, hypoxia-inducible factor-1alpha and vascularendothelial growth factor reduced late rectal injury induced byirradiation [J]. J Radiat Res,2009,50(3):233-239
[35]付凯飞,彭瑞云.肠放射性损伤的研究进展[J].中华放射医学与防护杂志,2004,24(1):79-81.
[36] Kilic D, Sayan H. The effect of granulocytemacrophage-colony stimulating factor on the prostaglandinE(2)-like activity of the small intestine of rat during total bodyirradiation [J]. Prostaglandins Leukot Essent Fatty Acids,2000,62(6):349-353.
[37]窦保凤，李双标，张金格.中药对大鼠放射性直肠损伤的作用机制研究[J].中国现代医生,2009,47(15):70-71.
[38]胡岳然,吴超权,陈楚平,等.盆腔肿瘤放疗中用参苓白术散防止放射性肠炎[J].实用癌症杂志,2004,19(3):317-318.
[39]翟瑞庆,翟红运.扶正止泻汤治疗放射性肠炎68例[J].上海中医药杂志,2008,42(11):43-45.
[40] Vaanane HK. Mesenchymal stem cell [J]. Ann Med,2005,37(7):469-479.
[41] Zuk PA. Stem cell research has only just begun [J]. Science,2001,293(5528):211-212.
[42] Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is asource of multipotent stem cells [J]. Mol Biol Cell,2002,13(12):4279-4295.
[43] Hussain I, Magd SA, Eremin O, et al. New approach to isolatemesenchymal stem cell (MSC) from human umbilical cordblood [J]. Cell Biol Int,2012,36(7):595-600.
[44] Salem HK, Thiemermann C. Mesenchymal stromal cells:current understanding and clinical status [J]. Stem Cells,2010,31(28):585-596.
[45] Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria fordefining multipotent mesenchymal stromal cells.TheInterational Society for Cellular Therapy position statement [J].Cytotherapy,2006,8(4):315-317.
[46] Song K, Wang Z, Li W, et al. In vitro culture, determination,and directed differentiation of adult adipose-derived stem cellstowards cardiomyocyte-like cells induced by angiotensin II [J].Appl Biochem Biotechnol,2013,170(2):459-470.
[47] Dave SD, Vanikar AV, Trivedi HL, et al. Extrinsic factorspromoting in vitro differentiation of insulin-secreting cells fromhuman adipose tissue-derived mesenchymal stem cells [J].Appl Biochem Biotechol,2013,170(4):962-971
[48] Qin Y, Zhou P, Zhou C, et al. The adipose-derivedlineage-negative cells are enriched mesenchymal stem cells andpromote limb ischemia recovery in mice [J]. Stem Cells Dev,23(4):363-371.
[49] Bruckner S, Tautenhahn HM, Winkler S, et al. Isolation andhepatocyte differentiation of mesenchymal stem cells fromporcine bone marrow―surgical waste as a novel MSC source[J]. Transplat Proc,2013,45(5):2056-2058.
[50] Li JF, Yin HL, Shuboy A, et al. Differentiation of hUC-MSCinto dopaminergic-like cells after transduction with hepatocytegrowth factor [J]. Mol Cell Biochem,2013,381(1-2):183-190.
[51] Park BS, Kim WS, Choi JS, et al. Hair growth stimulated byconditioned medium of adipose-derived stem cells is enhancedby hypoxia: evidence of increased growth factor secretion [J].Biomed Res,2010,31(1):27-34.
[52] Ji JF, He BP, Dheen ST, et al. Interations of chemokines andchemokine receptors mediate the migration of mesenchymalstem cells to the impaired site in the brain after hypoglossalnerve injury [J]. Stem cells,2004,22(3):415-427.
[53] Yagi H, Soto-Gutierrez A, Parekkadan B, et al. Mesenchymalstem cells: Mechanisms of immunemodulation and homing [J].Cell Transplant,2010,19(6):667-679.
[54] Zhang J, Gong JF, Zhang W, et al. Effects of transplated bonemarrow mesenchymal stem cells on the irradiated intestine ofmice [J]. J Biomed Sci,2008,15(5):585-594.
[55] Francois S, Bensidhoum M, Mouiseddine M, et al. Localirradiation not only induces homing of human mesenchymalstem cells at exposed sites but promotes their widespreadengrafment to multiple organs: a study of their quantitativedistribution after irradiation damage [J]. Stem cells,2006,24(4):1020-1029.
[56] Ren G, Zhao X, Zhang L, et al. Inflammatory cytokine-inducedintracellular adhesion molecular-1and vascular cell adhesionmolecular-1in mesenchymal stem cells are critical forimmunosuppression [J]. J Immunol,2010,184(5):2321-2328.
[57] Wang H, Yang YF, Zhao L, et al. Hepatocyte growth factorgene-modified mesenchymal stem cells reducedirradiation-induced lung injury [J]. Hum Gene Ther,2013,24(3):343-353.
[58] Xue J, Li X, Lu Y, et al. Gene-modified mesenchymal stemcells protect against radiation-induced lung injury [J]. Mol Ther,2013,21(2):456-465.
[59] Aguilar S, Scotton CJ, McNulty K, et al. Bone marrow stemcells expressing keratinocyte growth factor via an inducibleletivirus protests against bleomycin-induced pulmonary fibrosis[J]. PLoS One,2009,4(11): e8013.
[60] Rigol M, Solanes N, Farre J, et al. Effects of adiposetissue-derived stem cell therapy after myocardial infarction:impact of the route of administration [J]. J Card Fail,2010,16(4):357-366.
[61] Rigol M, Solanes N, Roura S, et al. Allogeneic adipose stemcell therapy in acute myocardial infarction [J]. Eur J Clin Invest,2014,44(1):83-92.
[62] Berardi GR, Rebelatto CK, Tavares HF, et al. Transplantationof SNAP-treated adipose tissue-derived stem cells improvescardiac function and induces neovascularization aftermyocardium infarct in rats [J]. Exp Mol Pathol,2011,90(2):149-156.
[63] Modonna R, Renna FV, Cellini C, et al. Age-dependentimpairment of number and angiogenic potential of adiposetissue-derived progenitor cells [J]. Eur J Clin Invest,2011,41(2):126-133.
[64] Lu F, Zhao X, Wu J, et al. MSCs transfected with hepatocytegrowth factor or vascular endothelial growth factor improvecardiac function in the infracted porcine heart by increasingangiogensis and reducing fibrosis [J]. Int J Cardiol,2013,167(6):2524-2532.
[65] Calligaris SD, Conget P. Intravenous administration of bonemarrow-derived multipotent mesenchymal stromal cells has aneutral effect on obesity-induced diabetic cardiomyopathy [J].Biol Res,2013,46(3):251-255.
[66] Cao Z, Zhang G, Wang F, et al. Protective effects ofmesenchymal stem cells with CXCR4up-regulation in a ratrenal transplantation [J]. PLoS One,2013,8(12): e82949.
[67] Duffy GP, Herron CC. Mesenchymal stem cells to augmenttherapeutic angiogenesis in hind-limb ischemia models: howimportant is their source [J]. Stem Cell Res Ther,2013,4(5):131.
[68] Yang SS, Kim NR, Park KB, et al. A phase I study of humancord blood-derived mesenchymal stem cell therapy in patientswith peripheral arterial occlusive disease [J]. Int J Stem Cells,2013,6(1):37-44.
[69] Matthes SM, Reimers K, Janssen I, et al. Intravenoustransplantation of mesenchymal stromal cells to enhanceperipheral nerve regeneration [J]. Biomed Res Int,2013,2013:573619.
[70]傅重洋,赵佳,曲巍.组织工程化神经修复周围神经创伤的应用[J].中国组织工程研究,2013,41:7335-7340.
[71]高平,孙占胜,王伯珉,等.骨髓间充质干细胞诱导成神经元样细胞移植治疗脊髓损伤[J].中国组织工程研究,2013,23:4256-4263.
[72] Tsai MJ, Tsai SK, Hu BR, et al. Recovery of neurologicalfunction of ischemic stroke by application of conditionedmedium of bone marrow mesenchymal stem cells derived fromnormal and cerebral ischemia rats [J]. J Biomed Sci,2014,21(1):5.
[73] Liao W, Xie J, Zhong J, et al. Therapeutic effects of humanumbilical cord multipotent mesenchymal stromal cells in a ratmodel of stroke [J]. Transplantation,2009,87(3):350-359.
[74] Wakabayashi K, Nagai A, Sheikh AM, et al. Transplantation ofhuman mesenchymal stem cells promotes fuctionalimprovement and increased expression of neurotrophic factorsin a rat focal cerebral ischemia model [J]. J Neurosci Res,2010,88(5):1017-25.
[75] Lee JK, Jin HK, Endo S, et al. Intracerebral transplantation ofbone marrow-derived mesenchymal stem cells reducesamyloid-beta deposition and rescues memory deficits inAlzhemier‘s disease mice by modulation of immune response[J]. Stem Cells,2010,28(2):329-343.
[76] Shin JY, Park HJ, Kim HN, et al. Mesenchymal stem cellsenhance autophagy and increase β-amyloid clearance inAlzheimer disease models [J]. Autophagy,2014,10(1):32-44.
[77] Lee HJ, Lee JK, Lee H, et al. Human umbilical cordblood-derived mesenchymal stem cells improveneuropathology and cognitive impairment in an Alzheimer‘sdisease mouse model through modulation ofneuroinflammation [J]. Neurobiol Aging,2012,33(3):588-602.
[78] Kusadasi N, Groeneveld AB. A perspective on mesenchymalstromal cell transplantation in the treatment of sepsis [J]. Shock,2013;40(5):352-7.
[79] Chang YS, Choi SJ, Ahn SY, et al. Timing of umbilical cordblood derived mesenchymal stem cells transplantationdetermines therapeutic efficacy in the neonatal hyperoxic lunginjury [J]. PLoS One,2013,8(1): e52419.
[80] Lyer SS, Co C, Rojas M. Mesenchymal stem cells andinflammatory lungdiseases [J]. Panminerva Med,2009,51(5):5-16.
[81] Antoniou KM, Papadaki HA, Soufla G, et al. Investigation ofbone marrow mesenchymal stem cells (BM MSCs)involvement in Idiopathic Pulmonary Fibrosis (IPF)[J]. RespirMed,2010,104(10):1535-1542.
[82] Toonke RL, Hare JM, Matthay MA, et al. Mesenchymal stemcells and idiopathic pulmonary fibrosis. Potential for clinicaltesting [J]. Am J Respir Crit Care Med,2013,188(2):133-140.
[83] Ma N, Gai H, Mei J, et al. Bone marrow mesenchymal stemcells can differentiate into type II alveolar epithelial cells invitro [J]. Cell Biol Int,2011,35(12):1261-1266.
[84] Bozyk PD, Moore BB. Prostaglandin E2and pathogenesis ofpulmonary fibrosis [J]. Am J Respir Cell Mol Biol,2011,45(3):445-452.
[85] Hyashi H, Abdollah S, Qiu Y, et al. The MAD-related proteinSmad7associats with the TGFbeta receptor and functions as anantagonist of TGFbeta signaling [J]. Cell,1997,89(7):1165-1173.
[86] Shukla MN, Rose JL, Ray R, et al. Hepatocyte growth factorinhibits epithelial to myofibroblast transition in lung cells viaSmad7[J]. Am J Respir Cell Mol Biol,2009,40(6):643-653.
[87] Sun Z, Gong X, Zhu H, et al. Inhibition of Wnt/β-cateninsignaling promotes engrafment of mesenchymal stem cells torepair lung injury [J]. J Cell Physiol,2014，229(2):213-224.
[88] Zimmerlin L, Park TS, Zambidis ET, et al. Mesenchymal stemcells secretome and regenerative therapy after cancer [J].Biochimie,2013,95(12):2235-2245.
[89] Zhao ZH, Xin SJ, Zhao JM, et al. Dynamic expression ofmatrix metalloproteinase-2, membrane type–matrixmetalloproteinase-2in experimental hepatic fibrosis and itsreversal in rat [J]. Zhonghua Shi Yan He Lin Chuang Bing DuXue Za Zhi,2004,18(4):328-331.
[90] Hardjo M, Miyazaki M, Sakaguchi M, et al. Suppression ofcarbon tetrachloride-induced liver fibrosis by transplantationof a clonal mesenchymal stem cell line derived from rat bonemarrow [J]. Cell Transplant,2009,18(1):89-99.
[91] Tsai PC, Fu TW, Chen YM, et al. The therapeutic potential ofhuman umbilical mesenchymal stem cells from Wharton‘s jellyin the treatment of rat liver fibrosis [J]. Liver Transpl,2009,15(5):484-495.
[92]柳林,杨海山,孙昱,等.自体脂肪间充质干细胞对晚期肝病影响的初步临床研究[J].中国实验诊断学,2007,11(4):473-476.
[93] Kuo TK, Hung SP, Chuang CH, et al. Stem cell therapy forliver disease: parameters governing the success of using bonemarrow mesenchymal stem cells [J]. Gastroenterology,2008,134(7):2111-21.
[94]常鹏宇,曲雅勤,刘拥军.自体脂肪干细胞在炎性肠病治疗中的应用前景[J].中国免疫学杂志,2013,29(4):443-448.
[95] Garcia-Olmo D, Garcia-Arranz M, Garcia LG, et al.Autologous stem cells transplantation for treatment ofrectovaginal fistula in perianal Crohn‘s disease: a newcell-based therapy [J]. Int J Colorectal Dis,2003,18(5):451-454.
[96] Garcia-Olmo D, Garcia-Arranz M, Herreros D, et al. A phase Iclinical trail of the treatment of Crohn‘s fistula by adiposemesenchymal stem cell transplantation [J]. Dis Colon Rectum,2005,48(7):1416-1423.
[97] Garcia-Olmo D, Herreros D, Pascual I, et al. Expandedadipose-derived stem cells for the treatment of complexperianal fistula: a phase II clinical trail [J]. Dis Colon Rectum,2009,52(1):79-86.
[98] Swart JF, de Roock S, Hofhuis FM, et al. Mesenchymal stemcell therapy in proteoglycan induced arthritis [J]. Ann RheumDis,2014,[Epub ahead of print].
[99]鲁琳,王丹丹,李霞,等.脐带间充质干细胞上调系统性红斑狼疮调节性T细胞的机制研究[J].中华医学杂志,2013,93(13):980-983.
[100] Nazarov C, Surdo J, Bauer SR, et al. Assessment ofimmunosuppressive activity of human mesenchymal stem cellsusing murine antigen specific CD4and CD8T cells in vitro [J].Stem Cell Res Ther,2013,4(5):128.
[101] Newell LF, Deans RJ, Maziarz RT. Adult adherent stromalcells in the management of graft–versus-host disease [J].Expert Opin Biol Ther,2014,14(2):231-246.
[102]乔淑敏,陈广华,王易,等.脐带间充质干细胞治疗儿童异基因造血干细胞移植后急性移植物抗宿主病疗效观察[J].中国实验血液学杂志,2013,21(3):716-720.
[103] Semont A, Mouiseddine M, Francois A, et al. Mesenchymalstem cells improve small intestinal integrity though regulationof endogenous epithelial cell homeostasis [J]. Cell Death Differ,2010,17(6):952-961.
[104] Saha S, Bhanja P, Kabarriti R, et al. Bone marrow stromal celltranslocation mitigates radiation-induced gastrointestinalsyndrome in mice [J]. PLoS One,2011,6(9): e24072.
[105] Goessling W, North TE, Loewer S, et al. Genetic interaction ofPGE2and Wnt signaling regulates development specificationof stem cells and regeration [J]. Cell,2009,136(6):1136-1147.
[106] van Es JH, Haegebar A, Kujala P, et al. A critical role for theWnt effector Tcf4in adult intestinal homeostasis self-renewal[J]. Mol Cell Biol,2012,32(10):1918-1927.
[107] Park CH, Moon Y, Shin CM, et al. Cyclic AMP suppressesmatix metalloproteinase-1expression through inhibition ofMAPK and GSK-3beta [J]. J Invest Dermatol,2010,130(8):2049-2056.
[108] Bettess MD, Dubois N, Murphy MJ, et al. c-Myc is required forthe formation of intestinal crypts but dispensable forhomeostasis of the adult intestinal epithelium [J]. Mol Cell Biol,2005,25(17):7868-7878.
[109] Kudo K, Liu Y, Takahashi K, et al. Transplantation ofmesenchymal stem cells to prevent radiation-induced intestinalinjury mice [J]. J Radiat Res,2010,51(1):73-79.
[110]曹晓沧,王邦茂,赵辉,等.脐带间充质干细胞移植对肠辐射损伤模型鼠治疗作用的实验研究[J].中国辐射卫生,2010,19(3):257-261.
[111] Lee RH, Kim B, Choi I, et al. Characterization and expressionanalysis of mesenchymal stem cells from human bone marrowand adipose tissue [J]. Cell Physiol Biochem,2004,14(4-6):311-324.
[112] Liotta F, Angeli R, Cosmi L, et al. Toll-like receptor3and4are expressed byhuman bone marrow-derived mesenchymalstem cells and can inhibit their T-cell modulatory activity byimparing Notch signaling [J]. Stem Cells,2008,26(1):279-289.
[113] Lombardo E, DelaRosa O, Mancheno-Corvo P, et al. Toll-likereceptor-mediated signaling in human adipose-derived stemcells: implications for immunogenicity and immunosuppressivepotential [J]. Tissue Eng Part A,2009,15(7):1579-1589.
[114] Wagner W, Wein F, Sekinger A, et al. Comparativecharacteristics of mesenchymal stem cells from human bonemarrow, adipose tissue, and umbilical cord blood [J]. ExpHematol,2005,33(11):1402-1416.
[115]钟雪云,陈云贤.脐带造血干细胞移植的伦理问题[J].中国医学伦理学,2000,5:61-62.
[116] Brzoska M, Geiger H, Gauer S, et al. Epithelial differentiationof human adipose tissue-derived adult stem cells [J]. BiochemBiophys Res Commun,2005,330(1):142-150.
[117] Ando Y, Inaba M, Sakaguchi Y, et al. Subcutaneous AdiposeTissue-Derived Stem Cells Facilitate Colonic MucosalRecovery from2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)–Induced Colitis in Rats [J]. Inflamm Bowel Dis,2008,14(6):826-838.
[118] Zangi L, Margalit R, Reich-Zeliger S, et al. Direct imaging ofimmune rejection and memory induction by allogeneicmesenchymal stromal cells [J]. Stem Cells,2009,27(11):2865-2874.
[119] Cao Y, Sun Z, Liao L, et al. Human adipose tissue-derived stemcells differentiate into endothelial cells in vitro and improvepostnatal neovascularization in vivo [J]. Biochem Biophy ResCommun,2005,332(2):370-379.
[120] Aggarwal S, Pittenger MF. Human mesenchymal stem cellsmodulate allogeneic immune cell response [J]. Blood,2005,105(4):1815-1822.
[121] Nemeth K, Leelahavanichkul A, Yuen PS, et al. Bone marrowstromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophage to increasetheir interleukin-10production [J]. Nat Med,2009,15(1):42-29.
[122] Maqqini J, Mirkin G, Boqnanni I, et al. Mouse bonemarrow-derived mesenchymal stromal cells turn activatedmacrophages into a regulatory–like profile [J]. PLoS One,2010,5(2): e9252.
[123] Gonzalez-Rey, Anderson P, Gonzalez MA, et al. Human adultstem cells derived from adipose tissue protect againstexperimental colitis and sepsis [J]. Gut,2009,58(7):929-939.
[124] Waterman RS, Tomchuck SL, Henkle SL, et al. A newmesenchymal stem cell (MSC) paradigm: polarization into apro-inflammatory MSC1or an immunosuppressive MSC2phenotype [J]. PLoS One,2010,5(4): e10088.
[125] Hwa Cho H, Bae YC, Jung JS. Role of toll-like receptors onhuman adipose-derived stromal cells [J]. Stem Cells,2006,24(12):2744-2752.
[126] Brittan M, Chance V, Elia G, et al. A regenerative role for bonemarrow following experimental colitis: contributiong toneovasculogenesis and myofibroblasts [J]. Gastroenterology,2005,128(7):1984-1995.
[127] Hamilton W, Coleman MG, Rubin G. Colorectal cancer [J].BMJ,2013,346: f3172.
[128] Potten CS, Booth C. The role of radiation-induced andspontaneous apoptosis in the homeostasis of the gastrointestinalepithelium: a brief review [J]. Comp Biochem Physiol BBiochem Mol Biol,1997,118(3):473-478.
[129] Hauer Jensen M, Sauer T, Reitan JB, et al. Late radiationenteropathy following split-dose irradiation of rat smallintestine [J]. Acta Radiol Oncol,1986,25(3):203-206.
[130]顾源,汤新星,张圆圆,等.电离辐射致大鼠肠上皮细胞磷脂变化的研究[J].中华放射医学与防护杂志,2013,33(5):457-462.
[131] Merritt AJ, Allen TD, Potten CS, et al. Apoptosis in smallintestinal epithelial from p53-null mice: evidence for delayed,p53-independent G2/M-associated cell death aftergamma-irradiation [J]. Oncogene,1997,14(23):2759-2766.
[132] Trott KR. Radiation risks from imaging of intestinal andabdominal inflammation [J]. Scand J Gastroenterol Suppl,1994,203:43-47.
[133] Sangiorgi E, Capecchi MR. Bmi1is expressed in vivo inintestinal stem cells [J]. Nat Genet,2008,40(7):915-920.
[134] Carlone DL, Breault DT. Tales from the crypt: the expandingrole of slow cycling intestinal stem cells [J]. Cell Stem Cell,2012,10(1):2-4.
[135] Tian H, Biehs B, Warming S, et al. A reserve stem cellpopulation in small intestine renders Lgr5-positve cellsdispensable [J]. Nature,2011,478(7368):255-259.
[136] Tekeda N, Jain R, LeBoeuf MR, et al. Interconversion betweenintestinal stem cell populations in distinct niches [J]. Science,2011,334(6061):1420-1424.
[137] Roth S, Fodde R. The nature of intestinal stem cells’ nature [J].EMBO Rep,2011,12(6):483-484.
[138] Lei NY, Jabaji Z, Wang J, et al. Intestinal subepithelialmyofibroblasts support the growth of intestinal epithelial stemcell [J]. PLoS One,2014,9(1): e84651.
[139] Lange C, Brunswig-Spickenheier B, Cappallo-Obermann H, etal. Radiation rescue: mesenchymal stromal cells protect fromlethal irradiation [J]. PLos One,2011,6(1): e14486.
[140] Chen L, Tredget EE, Wu PY, et al. Paracrine factors ofmesenchymal stem cells recruit macrophages and endotheliallineage cells and enhance wound healing [J]. PLoS One,2008,3(4): e1886.
[141] Naito H, Kidoya H, Sakimoto S, et al. Identification andcharacterization of a resident vascular stem/progenitor cellpopulation in preexisting blood vessels [J]. EMBO J,2012,31(4):842-855.
[142] Cribbs SK, Martin GS, Rojas M. Monitoring of endothelialdysfunction in critically ill patients: the role of endothelialprogenitor cells [J]. Curr Opin Crit Care,2008,14(3):354-360.
[143] Kim H, Cho HJ, Kim SW, et al. CD31+cells represent highlyangiogenic and vasculogenic cells in bone marrow: novel roleof nonendothelial CD31+cells in neovascularization and theirtherapeutic effects on ischemic vascular disease [J]. Circ Res,2010,107(5):602-614.
[144] Yang X, Cepko CL. Flk-1, a receptor for vascular endothelialgrowth factor(VEGF), is expressed by retinal progenitor cells[J]. J Neurosci,1996,16(19):6089-6099.
[145] Qiu W, Carson-Walter EB, Liu H, et al. PUMA regulatesintestinal progenitor cell radiosensitivity and gastrointestinalsyndrome [J]. Cell Stem Cell,2008,2(6):576-583.
[146] Iwata M, Madtes DK, Abrams K, et al. Late infusion of clonedmarrow fibroblasts stimulates endogenous recovery fromradiation-induced lung injury [J]. PLoS One,2013,8(3):e57179.
[147] Askari AT, Unzek S, Popovic ZB, et al. Effect of stromal–cell-derived factor1on stem-cell homing and tissueregeneration in ischaemic cardiomyopathy [J]. Lancet,2003,362(9385):697-703.
[148]常鹏宇,崔爽,曲雅勤.间充质干细胞修复放射性肠损伤的机制探讨[J].中华放射医学与防护杂志,2013,33(5):565-568.
[149] Ocuin M, Bamboat ZM, Balachandran VP, et al. NeutrophilIL-10suppresses peritoneal inflammatory monocytes duringpolymicrobial sepsis [J]. J Leukoc Biol,2011,89(3):423-432.
[150] Nauseef WM. Diagnostic assays for myeloperoxidase andmyeloperoxidase deficiency [J]. Methods Mol Biol,2014,1124:537-546.
[151] Uchiyama M, Jin X, Matsuda H, et al. An AgonisticAnti-BTLA mAb (3C10) Induced Generation ofIL-10-Dependent Regulatory CD4+T Cells and Prolongationof Murine Cardiac Allograft [J]. Transplantation,2014,97(3):301-309.
[152] Engela AU, Hoogduijn MJ, Boer K, et al. Humanadipose-tissue derived mesenchymal stem cells inducefunctional de-novo regulatory T cells with methylated FOXP3gene DNA [J]. Clin Exp Immunol,2013,173(2):343-354.
[153] Lax S, Ross EA, White A, et al. CD248expression onmesenchymal stromal cells is required for post-natal andinfection-dependent thymus remodeling and regeneration [J].FEBS Open Bio,2012,2:187-190.
[2]闵锐,李雨,潘真.辐射损伤的分类及诊断—介绍美国国家战略储备辐射工作组关于急性放射病治疗的建议之一[J].国外医学（放射医学核医学分册）,2005,29(4):179-185.
[3] Kennedy GD, Heise CP. Radiation colitis and proctitis [J]. ClinColon Rectal Surg,2007,20(1):64-72.
[4]刘国辉,康新,陈功,等.肠内营养对放射性肠炎患者肠屏障功能及机体免疫反应的影响[J].中华放射医学与防护杂志,2012,32(6):612-615.
[5]曾昭冲.腹盆部肿瘤放射治疗学[M].复旦大学出版社,2007:589.
[6] Langberg CW, Sauer T, Reitan JB, et al. Relationship betweenintestinal fibrosis and histopathologic and morphometricchanges in consequential and late radiation enteropathy [J].Acta Oncol,1996,35(1):81-87.
[7] Umar S. Intestinal stem cells [J]. Current gastroenterologyreports,2010,12(5):340-348.
[8] Barker N, van Es JH, Kuipers J, et al. Identification of stemcells in small intestine and colon by marker gene Lgr5[J].Nature,2007,449(7165):1003-1007.
[9] Potten CS. Stem cells in gastrointestinal epithelium: numbers,characteristics and death [J]. Philos Trans R Soc Lond B BiolSci,1998,353(1370):821-830.
[10] Sato T, Vries RG, Snippert HJ, et al. Single Lgr5stem cellsbuild crypt-villus structures in vitro without a mesenchymalniche [J]. Nature,2009,459(7244):262-265.
[11] Clevers H. Stem Cells: A unifying theory for the crypt [J].Nature,2013,495(7439):53-54.
[12] Sato T, Clevers H. Growing self-organizing mini-guts from asingle intestinal stem cell: mechanism and applications [J].Science,2013,340(6137):1190-1194.
[13] Sato T, van Es JH, Snippert HJ, et al. Paneth cells constitutethe niche for Lgr5stem cells in intestinal crypts [J]. Nature,2011,469(7330):415-418.
[14] Schepers AG, Vries R, van den Born M, et al. Lgr5intestinalstem cells havehigh telomerase activity and randomly segregatetheir chromosomes [J]. EMBO J,2011,30(6):1104-1109.
[15] Foltankova V, Legartova S, Kozubek S, et al. DNA-damageresponse in chromatin of ribosomal genes and the surroundinggenome [J]. Gene,2013,522(2):156-167.
[16] Ishizuka S, Martin K, Booth C, et al. Poly (ADP-ribose)polymerase-1is a survival factor for radiation-exposedintestinal epithelial stem cells in vivo [J]. Nucleic Acids Res,2003,31(21):6198-205.
[17] Yan KS, Chia LA, Li X, et al. The intestinal stem cell markersBmi1and Lgr5identify two functionally distinct population [J].Proc Natl Acad Sci USA,2012,109(2):81-87.
[18]王守安,张胜昌,田国忠,等.成人和胎儿回肠器官内微血管构筑[J].解剖学进展,2010,16(5):463-466.
[19] Paris F, Fuks Z, Kang A, et al. Endothelial apoptosis as theprimary lesion initiating intestinal radiation damage in mice [J].Science,2001,293(5528):293-297.
[20] Giblin JP, Hewlett LJ, Hannah MJ. Basal secretion of vonWillebrand factor from human endothelial cells [J]. Blood,2008,112(4):957-964.
[21] Wang J, Boerma M, Fu Q, et al. Significance of endothelialdysfunction in the pathogenesis of early and delayed radiationenteropathy [J]. World J Gastroenterol,2007,13(22):3047-3055.
[22] Hendry JH, Booth C, Potten CS. Endothelial cells and radiationgastrointestinal syndrome [J]. Science,2001,294(5546):1411.
[23] Rao RM, Yang L, Garcia-Cardena G, et al.Endothelial-dependent mechanism of leukocyte recruitment tovascular wall [J]. Cire Res,2007,101(3):234-47.
[24] Auletta JJ, Deans RJ, Bartholomew AM. Emerging roles formultipotent, bone marrow-derived stromal cells in host defense[J]. Blood,2012,119(8):1801-1809.
[25]毕迎惠,韩俊庆,盛巍,等.爱维治对急性放射性肠炎大鼠肠道修复作用的实验研究[J].山东大学学报（医学版）,2007,45(3):274-278.
[26]姜新,辛颖,刘野,等.爱维治保留灌肠在盆腔精确放射治疗中对直肠损伤的保护作用[J].中国老年学杂志,2013,33(18):4392-4394.
[27]叶霈智.放射性肠炎临床治疗现状评述[J].癌症进展,2010,8(1):49-52.
[28] Kountouras J, Zavos C. Recent advances in the management ofradiation colitis [J]. World Gastroenterol,2008,14(48):7289-7301.
[29]周岩冰,李世宽,张建立,等.严重放射性肠损伤28例的综合治疗[J].中华普通外科杂志,2002,17(2):719-720.
[30] Oh H, Seong J, Kim W, et al. Recombinant human epidermalgrowth factor (rh EGF) protects radiation-induced intestinalinjury in murine [J]. J Radiat Res,2010,51(5):535-541
[31] Tessner TG, Muhale F, Riehl TE, et al. Prostaglandin E2reduces radiation-induced epithelial apoptosis though amechanism involving AKT activation and bax translocation [J].J Clin Invest,2004,114(11):1676-85.
[32]王瑞娟,彭瑞云,高亚兵,等. IL-11保护中子照射后肠上皮损伤的Jak/STAT信号转导机制研究[J].细胞与分子免疫学杂志,2009,25(1):27-30.
[33] Cai Y, Wang W, Liang H, et al. Keratinocyte growth factorpretreatment prevents radiation-induced intestinal damage in amouse model [J]. Scand J Gastroenterol,2013,48(4):419-426.
[34] Liu Y, Kudo K, Abe Y, et al. Inhibition of transforming growthfactor-beta, hypoxia-inducible factor-1alpha and vascularendothelial growth factor reduced late rectal injury induced byirradiation [J]. J Radiat Res,2009,50(3):233-239
[35]付凯飞,彭瑞云.肠放射性损伤的研究进展[J].中华放射医学与防护杂志,2004,24(1):79-81.
[36] Kilic D, Sayan H. The effect of granulocytemacrophage-colony stimulating factor on the prostaglandinE(2)-like activity of the small intestine of rat during total bodyirradiation [J]. Prostaglandins Leukot Essent Fatty Acids,2000,62(6):349-353.
[37]窦保凤，李双标，张金格.中药对大鼠放射性直肠损伤的作用机制研究[J].中国现代医生,2009,47(15):70-71.
[38]胡岳然,吴超权,陈楚平,等.盆腔肿瘤放疗中用参苓白术散防止放射性肠炎[J].实用癌症杂志,2004,19(3):317-318.
[39]翟瑞庆,翟红运.扶正止泻汤治疗放射性肠炎68例[J].上海中医药杂志,2008,42(11):43-45.
[40] Vaanane HK. Mesenchymal stem cell [J]. Ann Med,2005,37(7):469-479.
[41] Zuk PA. Stem cell research has only just begun [J]. Science,2001,293(5528):211-212.
[42] Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is asource of multipotent stem cells [J]. Mol Biol Cell,2002,13(12):4279-4295.
[43] Hussain I, Magd SA, Eremin O, et al. New approach to isolatemesenchymal stem cell (MSC) from human umbilical cordblood [J]. Cell Biol Int,2012,36(7):595-600.
[44] Salem HK, Thiemermann C. Mesenchymal stromal cells:current understanding and clinical status [J]. Stem Cells,2010,31(28):585-596.
[45] Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria fordefining multipotent mesenchymal stromal cells.TheInterational Society for Cellular Therapy position statement [J].Cytotherapy,2006,8(4):315-317.
[46] Song K, Wang Z, Li W, et al. In vitro culture, determination,and directed differentiation of adult adipose-derived stem cellstowards cardiomyocyte-like cells induced by angiotensin II [J].Appl Biochem Biotechnol,2013,170(2):459-470.
[47] Dave SD, Vanikar AV, Trivedi HL, et al. Extrinsic factorspromoting in vitro differentiation of insulin-secreting cells fromhuman adipose tissue-derived mesenchymal stem cells [J].Appl Biochem Biotechol,2013,170(4):962-971
[48] Qin Y, Zhou P, Zhou C, et al. The adipose-derivedlineage-negative cells are enriched mesenchymal stem cells andpromote limb ischemia recovery in mice [J]. Stem Cells Dev,23(4):363-371.
[49] Bruckner S, Tautenhahn HM, Winkler S, et al. Isolation andhepatocyte differentiation of mesenchymal stem cells fromporcine bone marrow―surgical waste as a novel MSC source[J]. Transplat Proc,2013,45(5):2056-2058.
[50] Li JF, Yin HL, Shuboy A, et al. Differentiation of hUC-MSCinto dopaminergic-like cells after transduction with hepatocytegrowth factor [J]. Mol Cell Biochem,2013,381(1-2):183-190.
[51] Park BS, Kim WS, Choi JS, et al. Hair growth stimulated byconditioned medium of adipose-derived stem cells is enhancedby hypoxia: evidence of increased growth factor secretion [J].Biomed Res,2010,31(1):27-34.
[52] Ji JF, He BP, Dheen ST, et al. Interations of chemokines andchemokine receptors mediate the migration of mesenchymalstem cells to the impaired site in the brain after hypoglossalnerve injury [J]. Stem cells,2004,22(3):415-427.
[53] Yagi H, Soto-Gutierrez A, Parekkadan B, et al. Mesenchymalstem cells: Mechanisms of immunemodulation and homing [J].Cell Transplant,2010,19(6):667-679.
[54] Zhang J, Gong JF, Zhang W, et al. Effects of transplated bonemarrow mesenchymal stem cells on the irradiated intestine ofmice [J]. J Biomed Sci,2008,15(5):585-594.
[55] Francois S, Bensidhoum M, Mouiseddine M, et al. Localirradiation not only induces homing of human mesenchymalstem cells at exposed sites but promotes their widespreadengrafment to multiple organs: a study of their quantitativedistribution after irradiation damage [J]. Stem cells,2006,24(4):1020-1029.
[56] Ren G, Zhao X, Zhang L, et al. Inflammatory cytokine-inducedintracellular adhesion molecular-1and vascular cell adhesionmolecular-1in mesenchymal stem cells are critical forimmunosuppression [J]. J Immunol,2010,184(5):2321-2328.
[57] Wang H, Yang YF, Zhao L, et al. Hepatocyte growth factorgene-modified mesenchymal stem cells reducedirradiation-induced lung injury [J]. Hum Gene Ther,2013,24(3):343-353.
[58] Xue J, Li X, Lu Y, et al. Gene-modified mesenchymal stemcells protect against radiation-induced lung injury [J]. Mol Ther,2013,21(2):456-465.
[59] Aguilar S, Scotton CJ, McNulty K, et al. Bone marrow stemcells expressing keratinocyte growth factor via an inducibleletivirus protests against bleomycin-induced pulmonary fibrosis[J]. PLoS One,2009,4(11): e8013.
[60] Rigol M, Solanes N, Farre J, et al. Effects of adiposetissue-derived stem cell therapy after myocardial infarction:impact of the route of administration [J]. J Card Fail,2010,16(4):357-366.
[61] Rigol M, Solanes N, Roura S, et al. Allogeneic adipose stemcell therapy in acute myocardial infarction [J]. Eur J Clin Invest,2014,44(1):83-92.
[62] Berardi GR, Rebelatto CK, Tavares HF, et al. Transplantationof SNAP-treated adipose tissue-derived stem cells improvescardiac function and induces neovascularization aftermyocardium infarct in rats [J]. Exp Mol Pathol,2011,90(2):149-156.
[63] Modonna R, Renna FV, Cellini C, et al. Age-dependentimpairment of number and angiogenic potential of adiposetissue-derived progenitor cells [J]. Eur J Clin Invest,2011,41(2):126-133.
[64] Lu F, Zhao X, Wu J, et al. MSCs transfected with hepatocytegrowth factor or vascular endothelial growth factor improvecardiac function in the infracted porcine heart by increasingangiogensis and reducing fibrosis [J]. Int J Cardiol,2013,167(6):2524-2532.
[65] Calligaris SD, Conget P. Intravenous administration of bonemarrow-derived multipotent mesenchymal stromal cells has aneutral effect on obesity-induced diabetic cardiomyopathy [J].Biol Res,2013,46(3):251-255.
[66] Cao Z, Zhang G, Wang F, et al. Protective effects ofmesenchymal stem cells with CXCR4up-regulation in a ratrenal transplantation [J]. PLoS One,2013,8(12): e82949.
[67] Duffy GP, Herron CC. Mesenchymal stem cells to augmenttherapeutic angiogenesis in hind-limb ischemia models: howimportant is their source [J]. Stem Cell Res Ther,2013,4(5):131.
[68] Yang SS, Kim NR, Park KB, et al. A phase I study of humancord blood-derived mesenchymal stem cell therapy in patientswith peripheral arterial occlusive disease [J]. Int J Stem Cells,2013,6(1):37-44.
[69] Matthes SM, Reimers K, Janssen I, et al. Intravenoustransplantation of mesenchymal stromal cells to enhanceperipheral nerve regeneration [J]. Biomed Res Int,2013,2013:573619.
[70]傅重洋,赵佳,曲巍.组织工程化神经修复周围神经创伤的应用[J].中国组织工程研究,2013,41:7335-7340.
[71]高平,孙占胜,王伯珉,等.骨髓间充质干细胞诱导成神经元样细胞移植治疗脊髓损伤[J].中国组织工程研究,2013,23:4256-4263.
[72] Tsai MJ, Tsai SK, Hu BR, et al. Recovery of neurologicalfunction of ischemic stroke by application of conditionedmedium of bone marrow mesenchymal stem cells derived fromnormal and cerebral ischemia rats [J]. J Biomed Sci,2014,21(1):5.
[73] Liao W, Xie J, Zhong J, et al. Therapeutic effects of humanumbilical cord multipotent mesenchymal stromal cells in a ratmodel of stroke [J]. Transplantation,2009,87(3):350-359.
[74] Wakabayashi K, Nagai A, Sheikh AM, et al. Transplantation ofhuman mesenchymal stem cells promotes fuctionalimprovement and increased expression of neurotrophic factorsin a rat focal cerebral ischemia model [J]. J Neurosci Res,2010,88(5):1017-25.
[75] Lee JK, Jin HK, Endo S, et al. Intracerebral transplantation ofbone marrow-derived mesenchymal stem cells reducesamyloid-beta deposition and rescues memory deficits inAlzhemier‘s disease mice by modulation of immune response[J]. Stem Cells,2010,28(2):329-343.
[76] Shin JY, Park HJ, Kim HN, et al. Mesenchymal stem cellsenhance autophagy and increase β-amyloid clearance inAlzheimer disease models [J]. Autophagy,2014,10(1):32-44.
[77] Lee HJ, Lee JK, Lee H, et al. Human umbilical cordblood-derived mesenchymal stem cells improveneuropathology and cognitive impairment in an Alzheimer‘sdisease mouse model through modulation ofneuroinflammation [J]. Neurobiol Aging,2012,33(3):588-602.
[78] Kusadasi N, Groeneveld AB. A perspective on mesenchymalstromal cell transplantation in the treatment of sepsis [J]. Shock,2013;40(5):352-7.
[79] Chang YS, Choi SJ, Ahn SY, et al. Timing of umbilical cordblood derived mesenchymal stem cells transplantationdetermines therapeutic efficacy in the neonatal hyperoxic lunginjury [J]. PLoS One,2013,8(1): e52419.
[80] Lyer SS, Co C, Rojas M. Mesenchymal stem cells andinflammatory lungdiseases [J]. Panminerva Med,2009,51(5):5-16.
[81] Antoniou KM, Papadaki HA, Soufla G, et al. Investigation ofbone marrow mesenchymal stem cells (BM MSCs)involvement in Idiopathic Pulmonary Fibrosis (IPF)[J]. RespirMed,2010,104(10):1535-1542.
[82] Toonke RL, Hare JM, Matthay MA, et al. Mesenchymal stemcells and idiopathic pulmonary fibrosis. Potential for clinicaltesting [J]. Am J Respir Crit Care Med,2013,188(2):133-140.
[83] Ma N, Gai H, Mei J, et al. Bone marrow mesenchymal stemcells can differentiate into type II alveolar epithelial cells invitro [J]. Cell Biol Int,2011,35(12):1261-1266.
[84] Bozyk PD, Moore BB. Prostaglandin E2and pathogenesis ofpulmonary fibrosis [J]. Am J Respir Cell Mol Biol,2011,45(3):445-452.
[85] Hyashi H, Abdollah S, Qiu Y, et al. The MAD-related proteinSmad7associats with the TGFbeta receptor and functions as anantagonist of TGFbeta signaling [J]. Cell,1997,89(7):1165-1173.
[86] Shukla MN, Rose JL, Ray R, et al. Hepatocyte growth factorinhibits epithelial to myofibroblast transition in lung cells viaSmad7[J]. Am J Respir Cell Mol Biol,2009,40(6):643-653.
[87] Sun Z, Gong X, Zhu H, et al. Inhibition of Wnt/β-cateninsignaling promotes engrafment of mesenchymal stem cells torepair lung injury [J]. J Cell Physiol,2014，229(2):213-224.
[88] Zimmerlin L, Park TS, Zambidis ET, et al. Mesenchymal stemcells secretome and regenerative therapy after cancer [J].Biochimie,2013,95(12):2235-2245.
[89] Zhao ZH, Xin SJ, Zhao JM, et al. Dynamic expression ofmatrix metalloproteinase-2, membrane type–matrixmetalloproteinase-2in experimental hepatic fibrosis and itsreversal in rat [J]. Zhonghua Shi Yan He Lin Chuang Bing DuXue Za Zhi,2004,18(4):328-331.
[90] Hardjo M, Miyazaki M, Sakaguchi M, et al. Suppression ofcarbon tetrachloride-induced liver fibrosis by transplantationof a clonal mesenchymal stem cell line derived from rat bonemarrow [J]. Cell Transplant,2009,18(1):89-99.
[91] Tsai PC, Fu TW, Chen YM, et al. The therapeutic potential ofhuman umbilical mesenchymal stem cells from Wharton‘s jellyin the treatment of rat liver fibrosis [J]. Liver Transpl,2009,15(5):484-495.
[92]柳林,杨海山,孙昱,等.自体脂肪间充质干细胞对晚期肝病影响的初步临床研究[J].中国实验诊断学,2007,11(4):473-476.
[93] Kuo TK, Hung SP, Chuang CH, et al. Stem cell therapy forliver disease: parameters governing the success of using bonemarrow mesenchymal stem cells [J]. Gastroenterology,2008,134(7):2111-21.
[94]常鹏宇,曲雅勤,刘拥军.自体脂肪干细胞在炎性肠病治疗中的应用前景[J].中国免疫学杂志,2013,29(4):443-448.
[95] Garcia-Olmo D, Garcia-Arranz M, Garcia LG, et al.Autologous stem cells transplantation for treatment ofrectovaginal fistula in perianal Crohn‘s disease: a newcell-based therapy [J]. Int J Colorectal Dis,2003,18(5):451-454.
[96] Garcia-Olmo D, Garcia-Arranz M, Herreros D, et al. A phase Iclinical trail of the treatment of Crohn‘s fistula by adiposemesenchymal stem cell transplantation [J]. Dis Colon Rectum,2005,48(7):1416-1423.
[97] Garcia-Olmo D, Herreros D, Pascual I, et al. Expandedadipose-derived stem cells for the treatment of complexperianal fistula: a phase II clinical trail [J]. Dis Colon Rectum,2009,52(1):79-86.
[98] Swart JF, de Roock S, Hofhuis FM, et al. Mesenchymal stemcell therapy in proteoglycan induced arthritis [J]. Ann RheumDis,2014,[Epub ahead of print].
[99]鲁琳,王丹丹,李霞,等.脐带间充质干细胞上调系统性红斑狼疮调节性T细胞的机制研究[J].中华医学杂志,2013,93(13):980-983.
[100] Nazarov C, Surdo J, Bauer SR, et al. Assessment ofimmunosuppressive activity of human mesenchymal stem cellsusing murine antigen specific CD4and CD8T cells in vitro [J].Stem Cell Res Ther,2013,4(5):128.
[101] Newell LF, Deans RJ, Maziarz RT. Adult adherent stromalcells in the management of graft–versus-host disease [J].Expert Opin Biol Ther,2014,14(2):231-246.
[102]乔淑敏,陈广华,王易,等.脐带间充质干细胞治疗儿童异基因造血干细胞移植后急性移植物抗宿主病疗效观察[J].中国实验血液学杂志,2013,21(3):716-720.
[103] Semont A, Mouiseddine M, Francois A, et al. Mesenchymalstem cells improve small intestinal integrity though regulationof endogenous epithelial cell homeostasis [J]. Cell Death Differ,2010,17(6):952-961.
[104] Saha S, Bhanja P, Kabarriti R, et al. Bone marrow stromal celltranslocation mitigates radiation-induced gastrointestinalsyndrome in mice [J]. PLoS One,2011,6(9): e24072.
[105] Goessling W, North TE, Loewer S, et al. Genetic interaction ofPGE2and Wnt signaling regulates development specificationof stem cells and regeration [J]. Cell,2009,136(6):1136-1147.
[106] van Es JH, Haegebar A, Kujala P, et al. A critical role for theWnt effector Tcf4in adult intestinal homeostasis self-renewal[J]. Mol Cell Biol,2012,32(10):1918-1927.
[107] Park CH, Moon Y, Shin CM, et al. Cyclic AMP suppressesmatix metalloproteinase-1expression through inhibition ofMAPK and GSK-3beta [J]. J Invest Dermatol,2010,130(8):2049-2056.
[108] Bettess MD, Dubois N, Murphy MJ, et al. c-Myc is required forthe formation of intestinal crypts but dispensable forhomeostasis of the adult intestinal epithelium [J]. Mol Cell Biol,2005,25(17):7868-7878.
[109] Kudo K, Liu Y, Takahashi K, et al. Transplantation ofmesenchymal stem cells to prevent radiation-induced intestinalinjury mice [J]. J Radiat Res,2010,51(1):73-79.
[110]曹晓沧,王邦茂,赵辉,等.脐带间充质干细胞移植对肠辐射损伤模型鼠治疗作用的实验研究[J].中国辐射卫生,2010,19(3):257-261.
[111] Lee RH, Kim B, Choi I, et al. Characterization and expressionanalysis of mesenchymal stem cells from human bone marrowand adipose tissue [J]. Cell Physiol Biochem,2004,14(4-6):311-324.
[112] Liotta F, Angeli R, Cosmi L, et al. Toll-like receptor3and4are expressed byhuman bone marrow-derived mesenchymalstem cells and can inhibit their T-cell modulatory activity byimparing Notch signaling [J]. Stem Cells,2008,26(1):279-289.
[113] Lombardo E, DelaRosa O, Mancheno-Corvo P, et al. Toll-likereceptor-mediated signaling in human adipose-derived stemcells: implications for immunogenicity and immunosuppressivepotential [J]. Tissue Eng Part A,2009,15(7):1579-1589.
[114] Wagner W, Wein F, Sekinger A, et al. Comparativecharacteristics of mesenchymal stem cells from human bonemarrow, adipose tissue, and umbilical cord blood [J]. ExpHematol,2005,33(11):1402-1416.
[115]钟雪云,陈云贤.脐带造血干细胞移植的伦理问题[J].中国医学伦理学,2000,5:61-62.
[116] Brzoska M, Geiger H, Gauer S, et al. Epithelial differentiationof human adipose tissue-derived adult stem cells [J]. BiochemBiophys Res Commun,2005,330(1):142-150.
[117] Ando Y, Inaba M, Sakaguchi Y, et al. Subcutaneous AdiposeTissue-Derived Stem Cells Facilitate Colonic MucosalRecovery from2,4,6-Trinitrobenzene Sulfonic Acid (TNBS)–Induced Colitis in Rats [J]. Inflamm Bowel Dis,2008,14(6):826-838.
[118] Zangi L, Margalit R, Reich-Zeliger S, et al. Direct imaging ofimmune rejection and memory induction by allogeneicmesenchymal stromal cells [J]. Stem Cells,2009,27(11):2865-2874.
[119] Cao Y, Sun Z, Liao L, et al. Human adipose tissue-derived stemcells differentiate into endothelial cells in vitro and improvepostnatal neovascularization in vivo [J]. Biochem Biophy ResCommun,2005,332(2):370-379.
[120] Aggarwal S, Pittenger MF. Human mesenchymal stem cellsmodulate allogeneic immune cell response [J]. Blood,2005,105(4):1815-1822.
[121] Nemeth K, Leelahavanichkul A, Yuen PS, et al. Bone marrowstromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophage to increasetheir interleukin-10production [J]. Nat Med,2009,15(1):42-29.
[122] Maqqini J, Mirkin G, Boqnanni I, et al. Mouse bonemarrow-derived mesenchymal stromal cells turn activatedmacrophages into a regulatory–like profile [J]. PLoS One,2010,5(2): e9252.
[123] Gonzalez-Rey, Anderson P, Gonzalez MA, et al. Human adultstem cells derived from adipose tissue protect againstexperimental colitis and sepsis [J]. Gut,2009,58(7):929-939.
[124] Waterman RS, Tomchuck SL, Henkle SL, et al. A newmesenchymal stem cell (MSC) paradigm: polarization into apro-inflammatory MSC1or an immunosuppressive MSC2phenotype [J]. PLoS One,2010,5(4): e10088.
[125] Hwa Cho H, Bae YC, Jung JS. Role of toll-like receptors onhuman adipose-derived stromal cells [J]. Stem Cells,2006,24(12):2744-2752.
[126] Brittan M, Chance V, Elia G, et al. A regenerative role for bonemarrow following experimental colitis: contributiong toneovasculogenesis and myofibroblasts [J]. Gastroenterology,2005,128(7):1984-1995.
[127] Hamilton W, Coleman MG, Rubin G. Colorectal cancer [J].BMJ,2013,346: f3172.
[128] Potten CS, Booth C. The role of radiation-induced andspontaneous apoptosis in the homeostasis of the gastrointestinalepithelium: a brief review [J]. Comp Biochem Physiol BBiochem Mol Biol,1997,118(3):473-478.
[129] Hauer Jensen M, Sauer T, Reitan JB, et al. Late radiationenteropathy following split-dose irradiation of rat smallintestine [J]. Acta Radiol Oncol,1986,25(3):203-206.
[130]顾源,汤新星,张圆圆,等.电离辐射致大鼠肠上皮细胞磷脂变化的研究[J].中华放射医学与防护杂志,2013,33(5):457-462.
[131] Merritt AJ, Allen TD, Potten CS, et al. Apoptosis in smallintestinal epithelial from p53-null mice: evidence for delayed,p53-independent G2/M-associated cell death aftergamma-irradiation [J]. Oncogene,1997,14(23):2759-2766.
[132] Trott KR. Radiation risks from imaging of intestinal andabdominal inflammation [J]. Scand J Gastroenterol Suppl,1994,203:43-47.
[133] Sangiorgi E, Capecchi MR. Bmi1is expressed in vivo inintestinal stem cells [J]. Nat Genet,2008,40(7):915-920.
[134] Carlone DL, Breault DT. Tales from the crypt: the expandingrole of slow cycling intestinal stem cells [J]. Cell Stem Cell,2012,10(1):2-4.
[135] Tian H, Biehs B, Warming S, et al. A reserve stem cellpopulation in small intestine renders Lgr5-positve cellsdispensable [J]. Nature,2011,478(7368):255-259.
[136] Tekeda N, Jain R, LeBoeuf MR, et al. Interconversion betweenintestinal stem cell populations in distinct niches [J]. Science,2011,334(6061):1420-1424.
[137] Roth S, Fodde R. The nature of intestinal stem cells’ nature [J].EMBO Rep,2011,12(6):483-484.
[138] Lei NY, Jabaji Z, Wang J, et al. Intestinal subepithelialmyofibroblasts support the growth of intestinal epithelial stemcell [J]. PLoS One,2014,9(1): e84651.
[139] Lange C, Brunswig-Spickenheier B, Cappallo-Obermann H, etal. Radiation rescue: mesenchymal stromal cells protect fromlethal irradiation [J]. PLos One,2011,6(1): e14486.
[140] Chen L, Tredget EE, Wu PY, et al. Paracrine factors ofmesenchymal stem cells recruit macrophages and endotheliallineage cells and enhance wound healing [J]. PLoS One,2008,3(4): e1886.
[141] Naito H, Kidoya H, Sakimoto S, et al. Identification andcharacterization of a resident vascular stem/progenitor cellpopulation in preexisting blood vessels [J]. EMBO J,2012,31(4):842-855.
[142] Cribbs SK, Martin GS, Rojas M. Monitoring of endothelialdysfunction in critically ill patients: the role of endothelialprogenitor cells [J]. Curr Opin Crit Care,2008,14(3):354-360.
[143] Kim H, Cho HJ, Kim SW, et al. CD31+cells represent highlyangiogenic and vasculogenic cells in bone marrow: novel roleof nonendothelial CD31+cells in neovascularization and theirtherapeutic effects on ischemic vascular disease [J]. Circ Res,2010,107(5):602-614.
[144] Yang X, Cepko CL. Flk-1, a receptor for vascular endothelialgrowth factor(VEGF), is expressed by retinal progenitor cells[J]. J Neurosci,1996,16(19):6089-6099.
[145] Qiu W, Carson-Walter EB, Liu H, et al. PUMA regulatesintestinal progenitor cell radiosensitivity and gastrointestinalsyndrome [J]. Cell Stem Cell,2008,2(6):576-583.
[146] Iwata M, Madtes DK, Abrams K, et al. Late infusion of clonedmarrow fibroblasts stimulates endogenous recovery fromradiation-induced lung injury [J]. PLoS One,2013,8(3):e57179.
[147] Askari AT, Unzek S, Popovic ZB, et al. Effect of stromal–cell-derived factor1on stem-cell homing and tissueregeneration in ischaemic cardiomyopathy [J]. Lancet,2003,362(9385):697-703.
[148]常鹏宇,崔爽,曲雅勤.间充质干细胞修复放射性肠损伤的机制探讨[J].中华放射医学与防护杂志,2013,33(5):565-568.
[149] Ocuin M, Bamboat ZM, Balachandran VP, et al. NeutrophilIL-10suppresses peritoneal inflammatory monocytes duringpolymicrobial sepsis [J]. J Leukoc Biol,2011,89(3):423-432.
[150] Nauseef WM. Diagnostic assays for myeloperoxidase andmyeloperoxidase deficiency [J]. Methods Mol Biol,2014,1124:537-546.
[151] Uchiyama M, Jin X, Matsuda H, et al. An AgonisticAnti-BTLA mAb (3C10) Induced Generation ofIL-10-Dependent Regulatory CD4+T Cells and Prolongationof Murine Cardiac Allograft [J]. Transplantation,2014,97(3):301-309.
[152] Engela AU, Hoogduijn MJ, Boer K, et al. Humanadipose-tissue derived mesenchymal stem cells inducefunctional de-novo regulatory T cells with methylated FOXP3gene DNA [J]. Clin Exp Immunol,2013,173(2):343-354.
[153] Lax S, Ross EA, White A, et al. CD248expression onmesenchymal stromal cells is required for post-natal andinfection-dependent thymus remodeling and regeneration [J].FEBS Open Bio,2012,2:187-190.