Myogenic Properties of Human Mesenchymal Stem Cells Derived From Three Different Sources
Myogenic Properties of Human Mesenchymal Stem Cells Derived From Three Different Sources
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DOI：
10.3727/096368911x580554
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发表时间：
2012-01-01
影响因子：
3.3
通讯作者：
Knaan-Shanzer, Shoshan
中科院分区：
文献类型：
--
作者：
de la Garza-Rodea, Anabel S.;van der Velde-van Dijke, Ietje;Knaan-Shanzer, Shoshan
哺乳动物的间充质干细胞（MSC）已经从许多组织中分离出来，其特征在于它们具有分化成骨、软骨和脂肪的能力。已经用来源于一些组织的MSC实现了向其他谱系的细胞如骨骼肌、肌腱/韧带、神经组织和上皮的分化。这种能力是否由所有组织的MSC共享尚不清楚。因此，我们比较了三个人供体的脂肪组织（AT），骨髓（BM）和滑膜（SM）的间充质干细胞的成肌特性。我们的数据表明，来自三种组织的人MSC在表型、增殖能力和分化潜能方面存在差异。AT-MSCs的分裂率明显高于其他两种组织来源的MSCs。此外，在长期维持MSC增殖能力方面观察到明显的供体特异性差异。虽然与鼠成肌细胞的体外融合能力相似，但三种来源的MSC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-、BM-或SM-MSC移植到免疫缺陷小鼠的心脏毒素损伤的胫骨前肌（TAM）中揭示，在治疗后30天，在用AT-MSC治疗的TAM中杂交肌纤维的频率最高。我们在含有人类细胞核的混合肌纤维中发现了人类特异性β-血影蛋白和肌营养不良蛋白，这为MSC在再生小鼠骨骼肌中的肌源性编程提供了依据。为了进一步开发基于MSC的肌病治疗，AT-MSC似乎是最好的选择，因为它们对肌再生的有效贡献，它们的高离体扩增潜力，并且因为它们的收获比BM-或SM-MSC的要求低。
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 beta-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 beta-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.