脂肪间充质干细胞的生物学特性及潜在临床应用
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摘要
脂肪间充质干细胞(adipose-derived stem cells,ADSCs)是来源于脂肪组织的多能干细胞。具有自我更新和多向分化能力,且可塑性强、免疫原性低、可旁分泌多种生物活性因子,同时致畸致瘤风险也比较低,在适宜诱导条件下可以分化为成骨细胞、脂肪细胞、软骨细胞等。ADSCs已经广泛用于骨及软骨组织的修复,皮肤损伤的修复、糖尿病和免疫调节等疾病治疗。本文就ADSCs的生物学特性及临床应用进展作一综述。
Adipose-derived mesenchymal stem cells(ADSCs) are stem cells that derived from adipose.Like other adult stem cells,they have self-renewal capacity,multi-differentiation potential,plasticity,low immunogenicity,paracrine secretion of various biologically active factors and lower teratogenicity.Meanwhile they can be differentiated into osteoblasts cells,fat cells and chondrocytes cells under suitable induction conditions.Adipose-derived mesenchymal stem cells have been widely used in the repair of bone,cartilage tissue,skin damage,diabetes and immune regulation.This article reviews the clinical application of ADSCs.
Adipose-derived mesenchymal stem cells(ADSCs) are stem cells that derived from adipose.Like other adult stem cells,they have self-renewal capacity,multi-differentiation potential,plasticity,low immunogenicity,paracrine secretion of various biologically active factors and lower teratogenicity.Meanwhile they can be differentiated into osteoblasts cells,fat cells and chondrocytes cells under suitable induction conditions.Adipose-derived mesenchymal stem cells have been widely used in the repair of bone,cartilage tissue,skin damage,diabetes and immune regulation.This article reviews the clinical application of ADSCs.
引文
[1]美丽,刘少英,刘福艳,等.脂肪组织来源干细胞治疗骨关节炎研究进展[J].国际骨科学杂志,2016,37(2):102-105.
[2]于婷,陈薇.脂肪来源间充质干细胞研究进展[J].军事医学科学院院刊,2008,32(1):81-83.
[3]Dominici M,Le Blanc K,Mueller I,et al.Minimal criteria for defining multipotent mesenchymal stromal cells.The international society for cellular therapy position statement[J].Cytotherapy,2006,8(4):315-317.
[4]Yoshimura K,Shigeura T,Matsumoto D,et al.Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates[J].J Cell Physiol,2006,208(1):64-76.
[5]Trottier V,Marceau-Fortier G,Germain L,et al.IF-ATS collection:Using human adipose-derived stem/stromal cells for the production of new skin substitutes[J].Stem cells,2008,26(10):2713-2723.
[6]Uemura R,Xu M,Ahmad N,et al.Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling[J].Circulation Research,2006,98(11):1414-1421.
[7]Crisostomo PR,Markel TA,Wang M,et al.In the adult mesenchymal stem cell population,source gender is a biologically relevant aspect of protective power[J].Surgery,2007,142(2):215-221.
[8]Wang M,Tsai BM,Crisostomo PR,et al.Pretreatment with adult progenitor cells improves recovery and decreases native myocardial proinflammatory signaling after ischemia[J].Shock,2006,25(5):454-459.
[9]王维,黄玉成,陈燕辉.脂肪间充质干细胞对硬皮病小鼠皮损组织成纤维细胞增殖的影响及其机制[J].中国组织工程研究,2018,22(33):5249-5254.
[10]胡丽.人脂肪间充质干细胞来源的外泌体通过调控细胞外基质重建促进皮肤无瘢痕愈合[C].中华口腔医学会口腔医学科研管理分会第二次学术年会论文集,武汉,2017.
[11]刘培,胡振生,马玲,等.脂肪间充质干细胞条件培养基制备温敏凝胶外用治疗皮肤烫伤[J].中国组织工程研究,2017,21(30):4853-4860.
[12]谢敏,郝好杰,刘杰杰.脂肪间充质干细胞促进肝脏糖酵解对2型糖尿病大鼠高血糖的改善作用研究[J]解放军医学杂志,2016,41(7):539-543.
[13]李素燕,陈倩雅,邱友燕.2型糖尿病患者脂肪间充质干细胞成脂肪分化能力的实验研究[J].重庆医学,2018,47(4):456-459.
[14]唐敏.肥胖促进骨桥蛋白甲基化导致脂肪来源的间充质干细胞成脂分化[D].上海:第二军医大学,2017.
[15]杨晨.脂肪间充质干细胞移植改善糖尿病心肌病大鼠心肌损伤的研究[D].北京:中国人民解放军医学院,2017.
[16]靳丽媛.脂肪间充质干细胞促进巨噬细胞的极化修复糖尿病心肌病大鼠损伤心肌的研究[D].北京:中国人民解放军医学院,2017.
[17]王建军,樊艳,马爱群,等.人脂肪间充质干细胞的免疫调节作用[J].中国组织工程研究,2012,16(45):8430-8434.
[18]朱希山,台卫平,施薇,等.骨髓和脂肪来源间充质干细胞的免疫调节作用[J].中国组织工程研究,2011,15(36):6683-6686.
[19]Sato M,Uchida K,Nakajima H,et al.Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis[J].Arthritis Res Ther,2012,14(1):R31.
[20]孙玺淳,巩凡,牛东生,等.脂肪间充质干细胞结合透明质酸钠对兔骨性关节炎治疗的实验研究[J].中国矫形外科杂志,2013,21(19):1991-1997.
[21]韩健,殷振华,李富航,等.人自体脂肪间充质干细胞治疗骨关节炎的临床研究[J].实用骨科杂志,2017,23(3):235-239.
[22]罗欣,余丽梅.外泌体在间充质干细胞治疗骨性关节炎中的作用:新策略与新思路[J].中国组织工程研究,2018,22(1):140-145.
[23]宋卓悦,王洋,连晓磊.人脂肪间充质干细胞和滑膜间充质干细胞协同抑制炎性软骨细胞的退变[J].中国组织工程研究,2018,22(17):2661-2668.
[24]丁涛,汤峰林,陆淼,等.骨形态发生蛋白14成骨诱导脂肪间充质干细胞复合丝素蛋白/羟基磷灰石支架修复骨缺损[J].中国组织工程研究,2018,22(33):5309-5314.
[25]Huo D,Dong F,Yu W,et al.Ifferentiation of mesenchymal stem cell in the microenviroment of Retinitis pigmentosa[J].Int J Ophthalmol,2010,10(10):1851-1854.
[26]戴方方.联合脂化间充质干细胞移植对糖尿病视网膜病变大鼠血-视网膜屏障的影响[D].北京:北京协和医院,2016.
[27]高俊彦,张芸,李明,等.生长相关蛋白43基因修饰脂肪间充质干细胞对视网膜色素变性的修复及保护[J].中国组织工程研究,2017,21(25):3978-3983.
[28]Theis VS,Sripadam R,Ramani V,et al.Chronic radiation enteritis[J].Clinical Oncology,2010,22(1):70-83.
[29]Yang C,Chen HX,Zhou Y,et al.Manganese superoxide dismutase gene therapy protects against irradiationinduced intestinal injury[J].Curr Gene Ther,2013,13(5):305-314.
[30]Somosy Z,Horvath G,Telbisz A,et al.Morphological aspects of ionizing radiation response of small intestine[J].Micron,2002,33(2):167-178.
[31]Mouiseddine M,Francois S,Semont A,et al.Human mesenchymal stem cellshome specifically to radiationinjured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model[J].Br J Radiol,2007,80 Spec No1(special_issue_1):S49.
[32]Chang P,Qu Y,Liu Y,et al.Multi-therapeutic effects of human adipose derived mesenchymal stem cells on radiation-induced intestinal injury[J].Cell Death Dis,2013,4:e685.
[33]常鹏宇,脂肪间充质干细胞修复放射性肠损伤的实验研究[D].吉林:吉林大学,2014.
[34]林琳,孙雯,王丽双.间充质干细胞对人He La宫颈癌细胞生长的影响[J].中华医学杂志,2015,95(15):1175-1178.
[35]Cho JA,Park H,Kim HK,et al.Hyperthermia-treated mesenchymal stem cells exert antitumor effects on human carcinoma cell line[J].Cancer,2009,115(2):311-323.
[36]Li Z,Ye Z,Zhang X,et al.E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice[J].Oncotarget,2016,7(32):51815-51828.
[37]Abrate A,Buono R,Canu T,et al.Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression[J].Eur J Cancer,2014,50(14):2478-2488.
[38]Ho IA,Yulyana Y,Sia KC,et al.Matrix metalloproteinase-1-mediated mesenchymal stem cell tumor tropism is dependent on crosstalk with stromal derived growth factor 1/C-X-C chemokine receptor 4 axis[J].FASEB J,2014,28(10):4359-4368.
[39]Xu S,Menu E,DE Becker A,et al.Bone marrow-derived mesenchymal stromal cells are attracted by multiple myeloma cell-produced chemokine CCL25 and favor myeloma cell growth in vitro and in vivo[J].Stem Cells,2012,30(2):266-279.
[40]郑丽红,刘翊,朱雪琼.人脂肪间充质干细胞对宫颈癌细胞的趋化性[J].温州医科大学学报,2018,48(5):325-329.
[41]彭大颖,吴迪.肿瘤环境下人类脂肪间充质干细胞的旁分泌特征变化与肿瘤细胞侵袭的关系分析[J].中国现代药物应用,2017,11(7):60-62.
[42]谢青松,许信龙,魏晓捷,等.新型超顺磁性氧化铁在干细胞活体示踪中的应用研究[J].中国临床药理学与药物治疗学,2010,15(3):272-276.
[2]于婷,陈薇.脂肪来源间充质干细胞研究进展[J].军事医学科学院院刊,2008,32(1):81-83.
[3]Dominici M,Le Blanc K,Mueller I,et al.Minimal criteria for defining multipotent mesenchymal stromal cells.The international society for cellular therapy position statement[J].Cytotherapy,2006,8(4):315-317.
[4]Yoshimura K,Shigeura T,Matsumoto D,et al.Characterization of freshly isolated and cultured cells derived from the fatty and fluid portions of liposuction aspirates[J].J Cell Physiol,2006,208(1):64-76.
[5]Trottier V,Marceau-Fortier G,Germain L,et al.IF-ATS collection:Using human adipose-derived stem/stromal cells for the production of new skin substitutes[J].Stem cells,2008,26(10):2713-2723.
[6]Uemura R,Xu M,Ahmad N,et al.Bone marrow stem cells prevent left ventricular remodeling of ischemic heart through paracrine signaling[J].Circulation Research,2006,98(11):1414-1421.
[7]Crisostomo PR,Markel TA,Wang M,et al.In the adult mesenchymal stem cell population,source gender is a biologically relevant aspect of protective power[J].Surgery,2007,142(2):215-221.
[8]Wang M,Tsai BM,Crisostomo PR,et al.Pretreatment with adult progenitor cells improves recovery and decreases native myocardial proinflammatory signaling after ischemia[J].Shock,2006,25(5):454-459.
[9]王维,黄玉成,陈燕辉.脂肪间充质干细胞对硬皮病小鼠皮损组织成纤维细胞增殖的影响及其机制[J].中国组织工程研究,2018,22(33):5249-5254.
[10]胡丽.人脂肪间充质干细胞来源的外泌体通过调控细胞外基质重建促进皮肤无瘢痕愈合[C].中华口腔医学会口腔医学科研管理分会第二次学术年会论文集,武汉,2017.
[11]刘培,胡振生,马玲,等.脂肪间充质干细胞条件培养基制备温敏凝胶外用治疗皮肤烫伤[J].中国组织工程研究,2017,21(30):4853-4860.
[12]谢敏,郝好杰,刘杰杰.脂肪间充质干细胞促进肝脏糖酵解对2型糖尿病大鼠高血糖的改善作用研究[J]解放军医学杂志,2016,41(7):539-543.
[13]李素燕,陈倩雅,邱友燕.2型糖尿病患者脂肪间充质干细胞成脂肪分化能力的实验研究[J].重庆医学,2018,47(4):456-459.
[14]唐敏.肥胖促进骨桥蛋白甲基化导致脂肪来源的间充质干细胞成脂分化[D].上海:第二军医大学,2017.
[15]杨晨.脂肪间充质干细胞移植改善糖尿病心肌病大鼠心肌损伤的研究[D].北京:中国人民解放军医学院,2017.
[16]靳丽媛.脂肪间充质干细胞促进巨噬细胞的极化修复糖尿病心肌病大鼠损伤心肌的研究[D].北京:中国人民解放军医学院,2017.
[17]王建军,樊艳,马爱群,等.人脂肪间充质干细胞的免疫调节作用[J].中国组织工程研究,2012,16(45):8430-8434.
[18]朱希山,台卫平,施薇,等.骨髓和脂肪来源间充质干细胞的免疫调节作用[J].中国组织工程研究,2011,15(36):6683-6686.
[19]Sato M,Uchida K,Nakajima H,et al.Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis[J].Arthritis Res Ther,2012,14(1):R31.
[20]孙玺淳,巩凡,牛东生,等.脂肪间充质干细胞结合透明质酸钠对兔骨性关节炎治疗的实验研究[J].中国矫形外科杂志,2013,21(19):1991-1997.
[21]韩健,殷振华,李富航,等.人自体脂肪间充质干细胞治疗骨关节炎的临床研究[J].实用骨科杂志,2017,23(3):235-239.
[22]罗欣,余丽梅.外泌体在间充质干细胞治疗骨性关节炎中的作用:新策略与新思路[J].中国组织工程研究,2018,22(1):140-145.
[23]宋卓悦,王洋,连晓磊.人脂肪间充质干细胞和滑膜间充质干细胞协同抑制炎性软骨细胞的退变[J].中国组织工程研究,2018,22(17):2661-2668.
[24]丁涛,汤峰林,陆淼,等.骨形态发生蛋白14成骨诱导脂肪间充质干细胞复合丝素蛋白/羟基磷灰石支架修复骨缺损[J].中国组织工程研究,2018,22(33):5309-5314.
[25]Huo D,Dong F,Yu W,et al.Ifferentiation of mesenchymal stem cell in the microenviroment of Retinitis pigmentosa[J].Int J Ophthalmol,2010,10(10):1851-1854.
[26]戴方方.联合脂化间充质干细胞移植对糖尿病视网膜病变大鼠血-视网膜屏障的影响[D].北京:北京协和医院,2016.
[27]高俊彦,张芸,李明,等.生长相关蛋白43基因修饰脂肪间充质干细胞对视网膜色素变性的修复及保护[J].中国组织工程研究,2017,21(25):3978-3983.
[28]Theis VS,Sripadam R,Ramani V,et al.Chronic radiation enteritis[J].Clinical Oncology,2010,22(1):70-83.
[29]Yang C,Chen HX,Zhou Y,et al.Manganese superoxide dismutase gene therapy protects against irradiationinduced intestinal injury[J].Curr Gene Ther,2013,13(5):305-314.
[30]Somosy Z,Horvath G,Telbisz A,et al.Morphological aspects of ionizing radiation response of small intestine[J].Micron,2002,33(2):167-178.
[31]Mouiseddine M,Francois S,Semont A,et al.Human mesenchymal stem cellshome specifically to radiationinjured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model[J].Br J Radiol,2007,80 Spec No1(special_issue_1):S49.
[32]Chang P,Qu Y,Liu Y,et al.Multi-therapeutic effects of human adipose derived mesenchymal stem cells on radiation-induced intestinal injury[J].Cell Death Dis,2013,4:e685.
[33]常鹏宇,脂肪间充质干细胞修复放射性肠损伤的实验研究[D].吉林:吉林大学,2014.
[34]林琳,孙雯,王丽双.间充质干细胞对人He La宫颈癌细胞生长的影响[J].中华医学杂志,2015,95(15):1175-1178.
[35]Cho JA,Park H,Kim HK,et al.Hyperthermia-treated mesenchymal stem cells exert antitumor effects on human carcinoma cell line[J].Cancer,2009,115(2):311-323.
[36]Li Z,Ye Z,Zhang X,et al.E1A-engineered human umbilical cord mesenchymal stem cells as carriers and amplifiers for adenovirus suppress hepatocarcinoma in mice[J].Oncotarget,2016,7(32):51815-51828.
[37]Abrate A,Buono R,Canu T,et al.Mesenchymal stem cells expressing therapeutic genes induce autochthonous prostate tumour regression[J].Eur J Cancer,2014,50(14):2478-2488.
[38]Ho IA,Yulyana Y,Sia KC,et al.Matrix metalloproteinase-1-mediated mesenchymal stem cell tumor tropism is dependent on crosstalk with stromal derived growth factor 1/C-X-C chemokine receptor 4 axis[J].FASEB J,2014,28(10):4359-4368.
[39]Xu S,Menu E,DE Becker A,et al.Bone marrow-derived mesenchymal stromal cells are attracted by multiple myeloma cell-produced chemokine CCL25 and favor myeloma cell growth in vitro and in vivo[J].Stem Cells,2012,30(2):266-279.
[40]郑丽红,刘翊,朱雪琼.人脂肪间充质干细胞对宫颈癌细胞的趋化性[J].温州医科大学学报,2018,48(5):325-329.
[41]彭大颖,吴迪.肿瘤环境下人类脂肪间充质干细胞的旁分泌特征变化与肿瘤细胞侵袭的关系分析[J].中国现代药物应用,2017,11(7):60-62.
[42]谢青松,许信龙,魏晓捷,等.新型超顺磁性氧化铁在干细胞活体示踪中的应用研究[J].中国临床药理学与药物治疗学,2010,15(3):272-276.