Department of Biochemistry and Biophysics, Graduate School of Health Care Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Building 3, Bunkyo-ku, Tokyo 113-8510, Japan.
Center for iPS Cell Research and Application (CiRA), Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Stem Cell Reports. 2018 Feb 13;10(2):568-582. doi: 10.1016/j.stemcr.2017.12.013. Epub 2018 Jan 11.
Satellite cells function as precursor cells in mature skeletal muscle homeostasis and regeneration. In healthy tissue, these cells are maintained in a state of quiescence by a microenvironment formed by myofibers and basement membrane in which LAMININs (LMs) form a major component. In the present study, we evaluated the satellite cell microenvironment in vivo and found that these cells are encapsulated by LMα2-5. We sought to recapitulate this satellite cell niche in vitro by culturing satellite cells in the presence of recombinant LM-E8 fragments. We show that treatment with LM-E8 promotes proliferation of satellite cells in an undifferentiated state, through reduced phosphorylation of JNK and p38. On transplantation into injured muscle tissue, satellite cells cultured with LM-E8 promoted the regeneration of skeletal muscle. These findings represent an efficient method of culturing satellite cells for use in transplantation through the recapitulation of the satellite cell niche using recombinant LM-E8 fragments.
卫星细胞作为成熟骨骼肌稳态和再生的前体细胞发挥作用。在健康组织中，这些细胞被肌纤维和基膜形成的微环境维持在静止状态，其中层粘连蛋白（LMs）构成主要成分。在本研究中，我们评估了体内卫星细胞的微环境，发现这些细胞被 LMα2-5 包裹。我们试图通过在存在重组 LM-E8 片段的情况下培养卫星细胞来在体外再现这种卫星细胞生态位。我们表明，通过降低 JNK 和 p38 的磷酸化，LM-E8 处理促进了未分化状态下卫星细胞的增殖。在移植到损伤的肌肉组织中，用 LM-E8 培养的卫星细胞促进了骨骼肌的再生。这些发现代表了一种通过使用重组 LM-E8 片段再现卫星细胞生态位来培养用于移植的卫星细胞的有效方法。
