Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
Cell Transplant. 2012;21(1):153-73. doi: 10.3727/096368911X580554. Epub 2011 Jun 7.
Mesenchymal stem cells (MSCs) of mammals have been isolated from many tissues and are characterized by their aptitude to differentiate into bone, cartilage, and fat. Differentiation into cells of other lineages like skeletal muscle, tendon/ligament, nervous tissue, and epithelium has been attained with MSCs derived from some tissues. Whether such abilities are shared by MSCs of all tissues is unknown. We therefore compared for three human donors the myogenic properties of MSCs from adipose tissue (AT), bone marrow (BM), and synovial membrane (SM). Our data show that human MSCs derived from the three tissues differ in phenotype, proliferation capacity, and differentiation potential. The division rate of AT-derived MSCs (AT-MSCs) was distinctly higher than that of MSCs from the other two tissue sources. In addition, clear donor-specific differences in the long-term maintenance of MSC proliferation ability were observed. Although similar in their in vitro fusogenic capacity with murine myoblasts, MSCs of the three sources contributed to a different extent to skeletal muscle regeneration in vivo. Transplanting human AT-, BM-, or SM-MSCs previously transduced with a lentiviral vector encoding β-galactosidase into cardiotoxin-damaged tibialis anterior muscles (TAMs) of immunodeficient mice revealed that at 30 days after treatment the frequency of hybrid myofibers was highest in the TAMs treated with AT-MSCs. Our finding of human-specific β-spectrin and dystrophin in hybrid myofibers containing human nuclei argues for myogenic programming of MSCs in regenerating murine skeletal muscle. For the further development of MSC-based treatments of myopathies, AT-MSCs appear to be the best choice in view of their efficient contribution to myoregeneration, their high ex vivo expansion potential, and because their harvesting is less demanding than that of BM- or SM-MSCs.
哺乳动物的间充质干细胞（MSCs）已从许多组织中分离出来，并具有向骨、软骨和脂肪分化的能力。一些组织来源的 MSCs 已分化为成肌细胞、肌腱/韧带、神经组织和上皮细胞等其他谱系的细胞。是否所有组织的 MSCs 都具有这种能力尚不清楚。因此，我们比较了来自 3 位供体的脂肪组织（AT）、骨髓（BM）和滑膜（SM）的 MSCs 的成肌特性。我们的数据表明，来自这三种组织的人 MSCs 在表型、增殖能力和分化潜能方面存在差异。AT 来源的 MSCs（AT-MSCs）的分裂率明显高于其他两种组织来源的 MSC。此外，还观察到 MSC 增殖能力的长期维持存在明显的供体特异性差异。尽管与小鼠成肌细胞的体外融合能力相似，但来自这三种来源的 MSCs 在体内对骨骼肌再生的贡献程度不同。将先前用编码β-半乳糖苷酶的慢病毒载体转导的人 AT-MSCs、BM-MSCs 或 SM-MSCs 移植到免疫缺陷小鼠的心肌毒素损伤的胫骨前肌（TAMs）中，发现治疗 30 天后，用 AT-MSCs 处理的 TAMs 中杂交肌纤维的频率最高。在含有人核的杂交肌纤维中发现人特异性β- spectrin 和 dystrophin ，这表明 MSCs 在再生的鼠骨骼肌中进行了成肌编程。考虑到 AT-MSCs 对肌再生的有效贡献、其体外扩增潜力高，以及与 BM-MSCs 或 SM-MSCs 相比，其采集要求较低，因此对于肌病的 MSC 为基础的治疗方法的进一步发展，AT-MSCs 似乎是最佳选择。
