INSERM UMR940, Institut Universitaire d'Hématologie, 75475 Paris Cedex 10, France.
Stem Cells Int. 2012;2012:412610. doi: 10.1155/2012/412610. Epub 2012 Apr 23.
In human skeletal muscle, myoblasts represent the main population of myogenic progenitors. We previously showed that, beside their myogenic differentiation capacities, myoblasts also differentiate towards osteogenic and chondrogenic lineages, some properties generally considered being hallmarks of mesenchymal stem cells (MSCs). MSCs are also characterized by their immunosuppressive potential, through cell-cell contacts and soluble factors, including prostaglandin E-2 (PGE-2), transforming growth factor-β1 (TGF-β1), interleukine-10, or indoleamine 2,3-dioxygenase. We and others also reported that Galectin-1 (Gal-1) and Semaphorin-3A (Sema-3A) were involved in MSCs-mediated immunosuppression. Here, we show that human myoblasts induce a significant and dose-dependant proliferation inhibition, independently of PGE-2 and TGF-β1. Our experiments revealed that myoblasts, in culture or in situ in human muscles, expressed and secreted Gal-1 and Sema-3A. Furthermore, myoblasts immunosuppressive functions were reverted by using blocking antibodies against Gal-1 or Sema-3A. Together, these results demonstrate an unsuspected immunosuppressive effect of myoblasts that may open new therapeutic perspectives.
在人类骨骼肌中，成肌细胞代表了主要的成肌祖细胞群体。我们之前曾表明，除了具有成肌分化能力外，成肌细胞还向成骨细胞和成软骨细胞谱系分化，而这些特性通常被认为是间充质干细胞（MSCs）的特征。MSCs 还具有免疫抑制特性，通过细胞-细胞接触和可溶性因子，包括前列腺素 E-2（PGE-2）、转化生长因子-β1（TGF-β1）、白细胞介素-10 或吲哚胺 2,3-双加氧酶。我们和其他人还报道称，半乳糖凝集素-1（Gal-1）和 Sema-3A 参与了 MSC 介导的免疫抑制作用。在这里，我们表明人类成肌细胞诱导显著且剂量依赖性的增殖抑制，这与 PGE-2 和 TGF-β1 无关。我们的实验表明，成肌细胞在培养或人肌肉原位中表达和分泌 Gal-1 和 Sema-3A。此外，使用针对 Gal-1 或 Sema-3A 的阻断抗体可以逆转成肌细胞的免疫抑制功能。总之，这些结果表明成肌细胞具有意想不到的免疫抑制作用，这可能为新的治疗方法开辟了新的前景。
