Activin A expression regulates multipotency of mesenchymal progenitor cells.

Activin A expression regulates multipotency of mesenchymal progenitor cells.
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DOI:
10.1186/scrt11
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发表时间:
2010-05-04
影响因子:
7.5
通讯作者:
Tuan RS
Tuan RS
中科院分区:
医学2区
文献类型:
--
作者:
Djouad F;Jackson WM;Bobick BE;Janjanin S;Song Y;Huang GT;Tuan RS

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骨髓(BM)基质目前代表间充质祖细胞(MPC)的最常见和研究的来源;然而,也已从多种组织中分离出类似的成体祖细胞或干细胞。本研究的目的是评估来自不同组织的MPCs的功能相似性,并确定与其多能性相关的特定因素。为此,我们直接比较了从不同成人组织中分离的MPC,包括骨髓、扁桃体、肌肉和牙髓。我们首先检查和比较增殖率,免疫调节特性,和多分化潜能,这些MPC在体外。接下来,我们专门评估了来自四种来源的MPC中激活素A表达谱和激活素A:卵泡抑素比率。MPC的多向分化潜能与激活素A水平和/或激活素A:卵泡抑素比率相关。有趣的是,通过siRNA介导的激活素A敲低,显示激活素A是MPC的软骨形成和成骨分化所需的。这些发现有力地表明,激活素A在软骨形成和骨形成的早期阶段具有关键的分化相关作用,同时抑制MPC的脂肪形成。这种来自不同组织来源的MPC的比较分析还将骨髓来源的MPC确定为在多谱系分化和免疫抑制方面最有效的MPC,这是基于细胞的再生医学的两个关键要求。此外,这项研究暗示了激活素A作为MPC身份的功能标志物的意义。
Bone marrow (BM) stroma currently represents the most common and investigated source of mesenchymal progenitor cells (MPCs); however, comparable adult progenitor or stem cells have also been isolated from a wide variety of tissues. This study aims to assess the functional similarities of MPCs from different tissues and to identify specific factor(s) related to their multipotency. For this purpose, we directly compared MPCs isolated from different adult tissues, including bone marrow, tonsil, muscle, and dental pulp. We first examined and compared proliferation rates, immunomodulatory properties, and multidifferentiation potential of these MPCs in vitro. Next, we specifically evaluated activin A expression profile and activin A:follistatin ratio in MPCs from the four sources. The multidifferentiation potential of the MPCs is correlated with activin A level and/or the activin A:follistatin ratio. Interestingly, by siRNA-mediated activin A knockdown, activin A was shown to be required for the chondrogenic and osteogenic differentiation of MPCs. These findings strongly suggest that activin A has a pivotal differentiation-related role in the early stages of chondrogenesis and osteogenesis while inhibiting adipogenesis of MPCs. This comparative analysis of MPCs from different tissue sources also identifies bone marrow-derived MPCs as the most potent MPCs in terms of multilineage differentiation and immunosuppression, two key requirements in cell-based regenerative medicine. In addition, this study implicates the significance of activin A as a functional marker of MPC identity.
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