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从诱导多能干细胞体外生成血管壁典型间充质干细胞(VW-MSC) 通过 VW-MSC 特异性基因转移。

In Vitro Generation of Vascular Wall-Typical Mesenchymal Stem Cells (VW-MSC) from Murine Induced Pluripotent Stem Cells Through VW-MSC-Specific Gene Transfer.

机构信息

Institute for Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Essen, Germany.

Institute for Transfusion Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany.

出版信息

Methods Mol Biol. 2020;2155:83-97. doi: 10.1007/978-1-0716-0655-1_7.

Abstract

Among the adult stem cells, multipotent mesenchymal stem cells (MSCs) turned out to be a promising option for cell-based therapies for the treatment of various diseases including autoimmune and cardiovascular disorders. MSCs bear a high proliferation and differentiation capability and exert immunomodulatory functions while being still clinically safe. As tissue-resident stem cells, MSCs can be isolated from various tissue including peripheral or umbilical cord blood, placenta, blood, fetal liver, lung, adipose tissue, and blood vessels, although the most commonly used source for MSCs is the bone marrow. However, the proportion of MSCs in primary isolates from adult tissue biopsies is rather low, and therefore MSCs must be intensively expanded in vitro before the MSCs find particular use in therapies that may require extensive and repetitive cell replacement. Therefore, more easily accessible sources of MSCs are needed. Here, we present a detailed protocol to generate tissue-typical MSCs by direct linage conversion using transcription factors defining target MSC identity from murine induced pluripotent stem cells (iPSCs).

摘要

在成体干细胞中,多能间充质干细胞(MSCs)被证明是一种很有前途的细胞治疗选择,可用于治疗各种疾病,包括自身免疫性疾病和心血管疾病。MSCs 具有高增殖和分化能力,并发挥免疫调节功能,同时在临床上仍然安全。作为组织驻留干细胞,MSCs 可以从各种组织中分离出来,包括外周血或脐带血、胎盘、血液、胎儿肝脏、肺、脂肪组织和血管,尽管最常用的 MSCs 来源是骨髓。然而,从成人组织活检中分离出来的原代 MSCs 比例相当低,因此在 MSCs 特别用于可能需要广泛和重复细胞替代的治疗之前,必须在体外进行密集扩增。因此,需要更易获得的 MSCs 来源。在这里,我们提出了一种详细的方案,通过使用转录因子从鼠诱导多能干细胞(iPSCs)中直接谱系转化来生成组织典型的 MSCs,从而定义目标 MSC 特性。

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