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人脐带基质干细胞:帕金森病啮齿动物模型中的初步表征及移植效果

Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease.

作者信息

Weiss Mark L, Medicetty Satish, Bledsoe Amber R, Rachakatla Raja Shekar, Choi Michael, Merchav Shosh, Luo Yongquan, Rao Mahendra S, Velagaleti Gopalrao, Troyer Deryl

机构信息

Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506, USA.

出版信息

Stem Cells. 2006 Mar;24(3):781-92. doi: 10.1634/stemcells.2005-0330. Epub 2005 Oct 13.

Abstract

The umbilical cord contains an inexhaustible, noncontroversial source of stem cells for therapy. In the U.S., stem cells found in the umbilical cord are routinely placed into bio-hazardous waste after birth. Here, stem cells derived from human umbilical cord Wharton's Jelly, called umbilical cord matrix stem (UCMS) cells, are characterized. UCMS cells have several properties that make them of interest as a source of cells for therapeutic use. For example, they 1) can be isolated in large numbers, 2) are negative for CD34 and CD45, 3) grow robustly and can be frozen/thawed, 4) can be clonally expanded, and 5) can easily be engineered to express exogenous proteins. UCMS cells have genetic and surface markers of mesenchymal stem cells (positive for CD10, CD13, CD29, CD44, and CD90 and negative for CD14, CD33, CD56, CD31, CD34, CD45, and HLA-DR) and appear to be stable in terms of their surface marker expression in early passage (passages 4-8). Unlike traditional mesenchymal stem cells derived from adult bone marrow stromal cells, small populations of UCMS cells express endoglin (SH2, CD105) and CD49e at passage 8. UCMS cells express growth factors and angiogenic factors, suggesting that they may be used to treat neurodegenerative disease. To test the therapeutic value of UCMS cells, undifferentiated human UCMS cells were transplanted into the brains of hemiparkinsonian rats that were not immune-suppressed. UCMS cells ameliorated apomorphine-induced rotations in the pilot test. UCMS cells transplanted into normal rats did not produce brain tumors, rotational behavior, or a frank host immune rejection response. In summary, the umbilical cord matrix appears to be a rich, noncontroversial, and inexhaustible source of primitive mesenchymal stem cells.

摘要

脐带含有一种用于治疗的取之不尽、毫无争议的干细胞来源。在美国,出生后在脐带中发现的干细胞通常被当作生物危险废物处理。在此,对源自人脐带华通氏胶的干细胞,即脐带基质干细胞(UCMS细胞)进行了特性描述。UCMS细胞具有多种特性,使其成为一种有吸引力的治疗用细胞来源。例如,它们1)能够大量分离,2)CD34和CD45呈阴性,3)生长旺盛且可冻存/解冻,4)能够克隆扩增,5)能够轻易被改造以表达外源蛋白。UCMS细胞具有间充质干细胞的遗传和表面标志物(CD10、CD13、CD29、CD44和CD90呈阳性,CD14、CD33、CD56、CD31、CD34、CD45和HLA-DR呈阴性),并且在早期传代(第4 - 8代)时其表面标志物表达似乎是稳定的。与源自成人骨髓基质细胞的传统间充质干细胞不同,少量UCMS细胞在第8代时表达内皮糖蛋白(SH2,CD105)和CD49e。UCMS细胞表达生长因子和血管生成因子,这表明它们可能可用于治疗神经退行性疾病。为了测试UCMS细胞的治疗价值,将未分化的人UCMS细胞移植到未进行免疫抑制的偏侧帕金森病大鼠的大脑中。在初步试验中,UCMS细胞改善了阿扑吗啡诱导的旋转行为。移植到正常大鼠体内的UCMS细胞未产生脑肿瘤、旋转行为或明显的宿主免疫排斥反应。总之,脐带基质似乎是原始间充质干细胞的丰富、毫无争议且取之不尽的来源。

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