Skeletal Muscle Stem Cells Derived from Teratomas

摘要 多能干细胞为肌肉细胞疗法的最终发展带来了巨大的希望 疾病;然而，已经证明非常难以获得具有有意义的体内再生的细胞 来自未修饰的野生型（WT）多能干细胞的潜能。使用WT PSC的小鼠移植研究- 衍生的细胞是罕见的，目前在该领域的成功等同于在一个细胞中产生几百个纤维。 移植胫骨前肌，总纤维数为3- 4，000。我们最近发现当老鼠 PSC在体内分化成畸胎瘤，它们产生大量的骨骼肌干细胞， 这些细胞具有巨大的体内功能潜力，再生大部分TA肌肉， 移植后产生力量的肌肉纤维。我们提出了一系列旨在了解 这些细胞是如何产生的，是什么使它们独特，将这些发现转化为人类系统，并利用这些发现， 知识，以改善体外分化方案。

Abstract Pluripotent stem cells hold tremendous promise for the eventual development of cell therapies for muscle disease; however it has proven exceptionally difficult to derive cells with meaningful in vivo regeneration potential from unmodified wild type (WT) pluripotent stem cells. Mouse transplantation studies with WT PSC- derived cells are rare, and success in the field currently equates to generation of a few hundred fibers in a transplanted tibialis anterior muscle with 3-4,000 total fibers. We have recently discovered that when mouse PSCs are differentiated into teratomas in vivo, they generate large numbers of skeletal muscle stem cells, and these cells have tremendous in vivo functional potential, regenerating the great majority of the TA muscle with force-generating muscle fibers upon transplantation. We propose a series of studies aimed at understanding how these cells arise, what makes them unique, translating these findings to the human system, and using this knowledge to improve in vitro differentiation protocols.