干细胞治疗1型糖尿病研究进展

doi:10.16431/j.cnki.1671-7236.2015.11.040

摘要/Abstract

摘要： 1型糖尿病是一种具有遗传倾向的慢性病。该类型糖尿病是由胰岛β细胞受到自身免疫的攻击产生不可逆破坏所致,属于胰岛素依赖性糖尿病。传统的治疗方法有胰岛素注射治疗和胰腺胰岛移植等。近几年随着干细胞研究的发展,诱导干细胞分化形成可分泌胰岛素的类β细胞的技术日渐完善,这为治疗1型糖尿病提供了新的技术支持。文章阐述了1型糖尿病的发病机制及干细胞应用于糖尿病治疗的研究进展。

关键词: 干细胞; 1型糖尿病(T1DM); 胰岛素分泌细胞

Abstract: Type 1 diabetes mellitus (T1DM) is a chronic disease,which has an inherited tendency.T1DM is an insulin-dependent diabetes.Insulin-secreting β-cells of patients with T1DM are selectively and irreversibly destroyed by autoimmune,so that these cells lose their function to secrete insulin.Traditional methods to cure T1DM include insulin injections and pancreas islet transplantation.Recently with the development of stem cells technique,we can get insulin-secreting β-cells from different types of stem cells.These new techniques have provided a new chance to heal T1DM.The review summarizes thepathophysiology of T1DM and we also show some new advances in stem-cell-based approaches that could be applied to treat diabetes in the future.

Key words: stem cell; type 1 diabetes mellitus (T1DM); insulin-producing cell

中图分类号:

R587.1

樊亚男, 关伟军, 刘学东. 干细胞治疗1型糖尿病研究进展[J]. , 2015, 42(11): 3099-3104.

FAN Ya-nan, GUAN Wei-jun, LIU Xue-dong. Research Progress on Stem Cell Therapy for Type 1 Diabetes Mellitus[J]. , 2015, 42(11): 3099-3104.

参考文献

[1] Bluestone J A,Herold K,Eisenbarth G.Genetics,pathogenesis and clinical interventions in type 1 diabetes[J].Nature,2010,464(7293):1293-1300.
[2] Burton A R,Vincent E,Arnold P Y,et al.On the pathogenicity of autoantigen-specific T-cell receptors[J].Diabetes,2008,57(5):1321-1330.
[3] Seissler J,Scherbaum W A.Autoimmune diagnostics in diabetes mellitus[J].Clin Chem Lab Med,2006,44(2):133-137.
[4] Erlich H,Valdes A M,Noble J,et al.HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk:Analysis of the type 1 diabetes genetics consortium families[J].Diabetes,2008,57(4):1084-1092.
[5] 高会敏,蒙碧辉.1型糖尿病发病机制的研究进展[J].医学研究杂志,2009,38(1):4-7.
[6] Engman C,Wen Y,Meng W S,et al.Generation of antigen-specific Foxp3⁺ regulatory T-cells in vivo following administration of diabetes-reversing tolerogenic microspheres does not require provision of antigen in the formulation[J].Clinical Immunology,2015,158(1):77-87.
[7] 张贻宇,胡宇航,潘玲玲,等.1型糖尿病知识更新[J].糖尿病天地,2009,3(6):242-245.
[8] Quinn M J.Diabetes,diet and autonomic denervation[J].Med Hypotheses,2010,74(2):232-234.
[9] Cekin Y,Ozkaya E,Gulkesen H,et al.Investigation of enterovirus infections,autoimmune factors and HLA genotypes in patients with T1DM[J].Minerva Endocrinol,2014,39(1):67-74.
[10] Seemayer T,Oligny L,Tannenbaum G,et al.Animal model:Spontaneous diabetes mellitus in the BB Wistar rat[J].Am J Pathol,1980,101:485.
[11] 周晓朋,钟学礼,朱禧星,等.自发性糖尿病BB大鼠的发病特点及其胰岛病理改变[J].上海医科大学学报,1990,17(4):261-264.
[12] 张俊.NOD鼠Ⅰ型糖尿病的发病机理及免疫治疗[D].合肥:中国科学技术大学,2011.
[13] 中华医学会、中华医学会糖尿病学分会.胰岛素注射技术对治疗效果的影响[A].中华医学会糖尿病学分会教育管理研讨会暨2014国际糖尿病教育管理论坛会议摘要集[C].中华医学会、中华医学会糖尿病学分会,2014.
[14] Shapiro A M,Lakey J R,Ryan E A,et al.Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen[J].N Engl J Med,2000,343(4):230-238.
[15] 王珊珊,闫峰,赵小丽,等.干细胞的研究进展[J].中国畜牧兽医,2010,37(5):44-47.
[16] Kroon E,Martinson L A,Kadoya K,et al.Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo[J].Nature Biotechnology,2008,26(4):443-452.
[17] 邓守龙,彭涛,吕自力,等.哺乳动物胚胎干细胞研究进展[J].中国畜牧兽医,2009,36(9):86-93.
[18] Weissman I L.Translating stem and progenitor cell biology to the clinic:Barriers andopportunities[J].Science,2000,287(5457):1442-1446.
[19] Conrad S,Renninger M,Hennenlotter J,et al.Generation of pluripotent stem cells from adult human testis[J].Nature,2008,456(7220):344-349.
[20] Bonner W S,Li W C,Ouziel Y L,et al.β-cell growth and regeneration:Replication is only part of the story[J].Diabetes,2010,59(10):2340-2348.
[21] Bonner W S,Taneja M,Weir G C,et al.In vitro cultivation of human islets from expanded ductal tissue[J].Proc Natl Acad Sci USA,2000,97(14):7999-8004.
[22] 楚元奎,曹晖,王赟,等.胎猪胰腺干细胞体外诱导分化为胰岛素分泌细胞及其移植治疗裸鼠糖尿病的研究[J].农业生物技术学报,2011,19(1):9-17.
[23] Tang D Q,Cao L Z,Burkhardt B R,et al. In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow[J].Diabetes,2004,53(7):1721-1732.
[24] Gabr M M,Zakaria M M,Refaie A F,et al.Insulin-producing cells from adult human bone marrow mesenchymal stem cells control streptozotocin-induced diabetes in nude mice[J].Cell Transplant,2013,22(1):133-145.
[25] Wang H S,Shyu J F,Shen W S,et al.Transplantation of insulin-producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice[J].Cell Transplant,2011,20(3):455-466.
[26] Tsai P J,Wang H S,Shyr Y M,et al.Transplantation of insulin-producing cells from umbilical cord mesenchymal stem cells for the treatment of streptozotocin-induced diabetic rats[J].J Biomed Sci,2012,19:47.
[27] De Coppi P,Bartsch G,Siddiqui M M,et al.Isolation of amniotic stem cell lines with potential for therapy[J].Nat Biotechnol,2007,25(1):100-106.
[28] Zhang Y,Dou Z.Under a nonadherent state,bone marrow mesenchymal stem cells can be efficiently induced into functional islet-like cell clusters to normalize hyperglycemia in mice:A control study[J].Stem Cell Res Ther,2014,5(3):66.
[29] Jurewicz M,Yang S,Augello A,et al.Congenic mesenchymal stem cell therapy reverses hyperglycemia in experimental type 1 diabetes[J].Diabetes,2010,59(12):3139-3147.
[30] 廖荣荣,颉孝贤,马育芳,等.诱导多能干细胞技术在猪转基因研究中的应用前景[J].中国畜牧兽医,2013,40(6):90-95.
[31] Tateishi K,He J,Taranova O,et al.Generation of insulin-secreting islet-like clusters from human skin fibroblasts[J].J Biol Chem,2008,283(46):31601-31607.
[32] Raikwar S P,Kim E M,Sivitz W I,et al.Human iPS cell-derived insulin producing cells form vascularized organoids under the kidney capsules of diabetic mice[J].PLoS One,2015,10(1):e0116582.
[33] Zhang D,Jiang W,Liu M,et al.Highly efficient differentiation of human ES cells and iPS cells into mature pancreatic insulin-producing cells[J].Cell Research,2009,19(4):429-438.
[34] Nagaya M,Katsuta H,Kaneto H,et al.Adult mouse intrahepatic biliary epithelial cells induced in vitro to become insulin-producing cells[J].J Endocrinol,2009,201(1):37-47.
[35] Aviv V,Meivar-Levy I,Rachmut I H,et al.Exendin-4 promotes liver cell proliferation and enhances the PDX-1-induced liver to pancreas transdifferentiation process[J].J Biol Chem,2009,284(48):33509-33520.
[36] Yechoor V,Liu V,Paul A,et al.Gene therapy with neurogenin 3 and betacellulin reverses major metabolic problems in insulin-deficient diabetic mice[J].Endocrinology,2009,150(11):4863-4873.
[37] Zhou Q,Brown J,Kanarek A,et al.In vivo reprogramming of adult pancreatic exocrine cells to beta-cells[J].Nature,2008,455(7213):627-632.