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人类间充质干细胞的异质性和功能多样性的新见解。

New insights into the heterogeneity and functional diversity of human mesenchymal stem cells.

作者信息

Han Z C, Du W J, Han Z B, Liang L

机构信息

National Engineering Center of Stem Cells, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.

Beijing Institute of Health and Stem Cells, Beijing, China.

出版信息

Biomed Mater Eng. 2017;28(s1):S29-S45. doi: 10.3233/BME-171622.

DOI:10.3233/BME-171622
PMID:28372276
Abstract

Mesenchymal stem cells (MSCs) are being tested in several biological systems and clinical settings with the aim of exploring their therapeutic potentials for a variety of diseases. MSCs are also known to be heterogeneous populations with variable functions. In the context of this multidimensional complexity, a recurrent question is what source or population of MSCs is suitable for specific clinical indications. Here, we reported that the biological features of MSCs varied with the individual donor, the tissue source, the culture condition and the subpopulations. Placental chorionic villi (CV) derived MSCs exhibited superior activities of immunomodulation and pro-angiogenesis compared to MSCs derived from bone marrow (BM), adipose and umbilical cord (UC). We identified a subpopulation of CD106(VCAM-1)+MSCs, which are present richly in placental CV, moderately in BM, and lowly in adipose and UC. The CD106+MSCs possess significantly increased immunomodutory and pro-angiogenic activities compared to CD106-MSCs. Analysis of gene expression and cytokine secretion revealed that CD106+MSCs highly expressed several immnumodulatory and pro-angiogenic cytokines. Our data offer new insights on the identification and selection of suitable source or population of MSCs for clinical applications. Further efforts should be concentrated on standardizing methods which will ultimately allow the validation of MSC products with defined biomarkers as predictive of potency in suitable pre-clinical models and clinical settings.

摘要

间充质干细胞(MSCs)正在多个生物系统和临床环境中进行测试,目的是探索其对多种疾病的治疗潜力。已知MSCs是具有可变功能的异质群体。在这种多维复杂性的背景下,一个反复出现的问题是哪种来源或类型的MSCs适合特定的临床适应症。在此,我们报告MSCs的生物学特征随个体供体、组织来源、培养条件和亚群的不同而有所变化。与来自骨髓(BM)、脂肪和脐带(UC)的MSCs相比,胎盘绒毛膜(CV)来源的MSCs表现出更强的免疫调节和促血管生成活性。我们鉴定出一个CD106(血管细胞黏附分子-1)+ MSCs亚群,其在胎盘CV中大量存在,在BM中中等存在,而在脂肪和UC中含量较低。与CD106 - MSCs相比,CD106 + MSCs具有显著增强的免疫调节和促血管生成活性。基因表达和细胞因子分泌分析显示,CD106 + MSCs高表达几种免疫调节和促血管生成细胞因子。我们的数据为临床应用中合适的MSCs来源或类型的鉴定和选择提供了新见解。应进一步致力于标准化方法,这最终将允许在合适的临床前模型和临床环境中,用确定的生物标志物验证MSCs产品的效力。

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