Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
Stem Cell Res Ther. 2010 May 4;1(2):11. doi: 10.1186/scrt11.
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.
骨髓(BM)基质目前是最常见和研究最多的间充质祖细胞(MPCs)来源;然而,也已经从各种组织中分离出了相当数量的成体祖细胞或干细胞。本研究旨在评估不同组织来源的 MPC 之间的功能相似性,并确定与它们多能性相关的特定因子。
为此,我们直接比较了来自不同成年组织的 MPC,包括骨髓、扁桃体、肌肉和牙髓。我们首先检查并比较了这些 MPC 在体外的增殖率、免疫调节特性和多向分化潜能。接下来,我们特别评估了四个来源的 MPC 中激活素 A 的表达谱和激活素 A:卵泡抑素比。
MPC 的多向分化潜能与激活素 A 水平和/或激活素 A:卵泡抑素比相关。有趣的是,通过 siRNA 介导的激活素 A 敲低,激活素 A 被证明是 MPC 软骨和成骨分化所必需的。这些发现强烈表明,激活素 A 在软骨发生和骨发生的早期阶段具有关键的分化相关作用,同时抑制 MPC 的脂肪生成。
对不同组织来源的 MPC 的这种比较分析还确定了骨髓来源的 MPC 是多谱系分化和免疫抑制方面最有潜力的 MPC,这是细胞再生医学的两个关键要求。此外,本研究表明激活素 A 作为 MPC 特征的功能标志物具有重要意义。