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，事实证明，获得有意义的体内再生细胞极其困难 来自未经修饰的野生型(WT)多能干细胞的潜力。WT-PSC-小鼠移植研究 衍生细胞很少见，目前在这一领域的成功相当于在一年中产生数百根纤维 移植的胫前肌总纤维数为3~4,000。我们最近发现，当老鼠 PSCs在体内分化为畸胎瘤，产生大量的骨骼肌干细胞， 这些细胞在体内具有巨大的功能潜力，可以再生绝大多数TA肌肉 移植后产生力量的肌肉纤维。我们提出了一系列研究，旨在了解 这些细胞是如何产生的，是什么使它们独一无二，将这些发现转化为人类系统，并使用 改进体外分化方案的知识。

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.