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人工模拟胰腺微环境诱导骨髓间充质干细胞分化为胰岛素产生细胞 被引量:2

Mesenchymal stem cells trans-differentiate to insulin-producing cells upon microenvironment manipulation in vitro
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摘要 目的:探讨人工模拟胰腺微环境诱导下骨髓间充质干细胞是否可以转分化为胰岛素产生细胞,并评价其功能。方法:采集兔骨髓间充质干细胞,分为2组。实验组将胰腺碎片整合到镍包被的微载体中,重建胰腺微环境,进行细胞培养,对照组为同期培养的未经诱导的细胞。骨髓间充质干细胞在微环境中培养3~4周后,观察是否有胰岛样细胞团形成。ELISA法检测细胞悬液中胰岛素含量,荧光免疫组化检测细胞团胰岛素和C-肽蛋白的表达,荧光原位杂交(FISH)检测胰岛素和C-肽mRNA的表达,流式细胞仪检测分化的细胞在高糖环境下继续培养3周是否发生凋亡。结果:培养3~4周后倒置显微镜下观察到胰岛样细胞团。实验组基础相胰岛素分泌量为(308.50±14.54)mIU/L,在高糖刺激下为(414.30±28.94)mIU/L,2者相比,差异有统计学意义(t=5.68,P<0.01);高糖刺激下实验组的胰岛素分泌量高于对照组的(5.21±1.04)mIU/L(t=34.60,P<0.01)。分化的胰岛样细胞团表达C-肽和胰岛素mRNA与蛋白。分化的细胞在高糖环境下继续培养3周未发生凋亡。结论:人工模拟胰腺微环境可以诱导骨髓间充质干细胞转分化为有功能的胰岛素产生细胞,有望替代胰岛细胞治疗糖尿病。 Aim:To observe whether mesenchymal stem cells(MSCs) could trans-differentiate to insulin-producing cells under manipulated microenvironment and assess their function.Methods:We delivered pancreatic pieces into Niobium-Coated Dynamatrix to construct a simulated pancreatic microenvironment.MSCs cultured upon simulated pancreatic microenvironment were selected as experimental group. MSCs cultured without induction at the same period were selected as control group.Bone marrow derived MSCs were cultured upon the...
出处 《郑州大学学报(医学版)》 CAS 北大核心 2009年第5期960-963,共4页 Journal of Zhengzhou University(Medical Sciences)
基金 国家973专项研究基金资助项目2004CCA01500 河南省教育厅自然科学基金资助项目2007310014
关键词 骨髓间充质干细胞 转分化 微环境 胰岛素产生细胞 mesenchymal stem cells trans-differentiation microenvironment insulin-producing cells
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  • 1任宁,王新平,张文治.骨髓间充质干细胞向神经细胞分化的研究进展[J].国际脑血管病杂志,2006,14(1):65-68. 被引量:1
  • 2王向鹏,杨智勇,王廷华,王进昆.神经生长因子和脑源性神经营养因子在脑胶质瘤内的表达[J].国际神经病学神经外科学杂志,2006,33(2):99-102. 被引量:13
  • 3何旭,王心蕊,张海英,牛云,李玉林.人骨髓间充质干细胞体外定向诱导分化为脂肪细胞方法的建立[J].吉林大学学报(医学版),2006,32(3):530-532. 被引量:10
  • 4Ianus A, Holz GG, Theise ND, Hussain MA. In vivo derivation of glucose - competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 2003; 111:843-850.
  • 5Kolb H, Burkart V. Nicotinamide in type 1 diabetes. Mechanism of action revisited. Diabetes Care 1999; 22(Suppl 2):B16-20.
  • 6Rajagopal J, Anderson WJ, Kume S, Martinez OI, Melton DA.Insulin staining of ES cells progeny from insulin uptake. Science 2003; 299:363.
  • 7Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, Scott EW. Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 2000; 416:542-545.
  • 8Spees JL, Olson SD, Ylostalo J, Lynch PJ, Smith J, Perry A,Peister A, Wang MY, Prockop DJ. Differentiation, cell fusion,and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc Natl Acad Sci U S A 2003; 100: 2397-2402.
  • 9Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki KL, Tzukerman M. Insulin production by human embryonic stem cells. Diabetes 2001; 50:1691-1697.
  • 10Hori Y, Rulifson IC, Tsai BC, Heit JJ, Cahoy JD, Kim SK.Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci U S A 2002; 99:16105-16110.

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  • 1Soria B. In-vitro differentiation of pancreatic beta cells[J]. Differentiation 2001, 68 (4/5) : 205-219,.
  • 2Lee J, Han DJ, Kim SC, et al. In human adipose tissue derived stem pancreatic phenotype by regenerating Bioehem Biophy Res Commun, 2008, vitro differentiation of cells into cells with pancreas extract[J].375 (4): 547-551.
  • 3Lumelsky N, Blondel O, Laeng P, et al. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets [J]. Science, 2001, 292 (5520):1389- 1394.
  • 4Wagner RT, Lewis J, Cooney A, et al. Stem cell approaches for the treatment of type 1 diabetes mellitus [J]. Transl Res, 2010, 156 (3): 169-179.
  • 5Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells [J]. Mol Biol Cell, 2002, 13 (12): 4279-4295.
  • 6Timper K, Seboek D, Eberhardt M, et al. Human adipose tissue derived mesenchymal stem cells differentiate into insulin, somatostatin, and glueagons expressing cells [J].Biochem Biophys Res Commun, 2006, 341 (4): 1135-1140.
  • 7Wang GS, Kauri LM, Patrick C, et al. Enhanced islet expansion by beta cell proliferation in young diabetes prone rats fed a protective diet [J]. J Cell Physiol, 2010, 224 (2) 501-508.
  • 8Borelli MI, Del Zotto H, Flores LE, et al. Transcription, expression and tissue binding in vivo of INGAP and INGAP- related peptide in normal hamsters [J].Regul Pept, 2007, 40 (3), 192-197.
  • 9Borelli MI, Stoppiglia LF, Rezende LF, et al. INGAP- related pentadecapeptide: its modulatory ef{eet upon insulin secretion[J]. Regul Pept, 2005, 31 (1 3): 97-102.
  • 10Rosenberg L, Lipsett M, Yoon pentadecapeptide fragment of islet protein increases beta cell mass and C57BL/6J mice [J]. Ann Surg, 2004 JW, et al. A neogenesis-associated reverses diabetes in 40 (5): 875-884.

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