Skeletal Muscle Stem Cells Derived from Teratomas

源自畸胎瘤的骨骼肌干细胞

• 批准号: 10627944
• 负责人: Michael Kyba
• 金额: $ 43.05万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10627944
• 关键词: Address; Advanced Development; Cell Differentiation process; Cell Therapy; Cells; Data; Development; Environment; Equation; Fiber; Generations; Glean; Histologic; Human; In Vitro; Knowledge; Label; Literature; Maps; Mediating; Methods; Mus; Muscle; Muscle Fibers; Muscle satellite cell; Myopathy; Natural regeneration; Pluripotent Stem Cells; Population; Public Health; Regenerative Medicine; Risk; Series; Signal Transduction; Signaling Protein; Skeletal Development; Skeletal Muscle; Surface; System; Teratoma; Time; Tissues; Translating; Transplantation; differentiation protocol; human pluripotent stem cell; improved; in vivo; in vivo regeneration; induced pluripotent stem cell; insight; muscle regeneration; muscle transplantation; novel; progenitor; regeneration potential; regenerative therapy; single cell sequencing; single-cell RNA sequencing; stem cell differentiation; stem cells; success; tibialis anterior muscle; tool

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.

抽象的 多能干细胞为肌肉细胞疗法的最终发展带来巨大希望 疾病;然而，事实证明，获得具有有意义的体内再生能力的细胞极其困难 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 衍生细胞非常罕见，目前该领域的成功相当于在一个细胞中产生数百根纤维 移植胫骨前肌，总纤维数为3-4,000。我们最近发现，当鼠标 PSC在体内分化为畸胎瘤，产生大量骨骼肌干细胞，并 这些细胞具有巨大的体内功能潜力，可再生大部分 TA 肌肉 移植后产生力的肌纤维。我们提出了一系列旨在了解 这些细胞是如何产生的，它们有何独特之处，将这些发现转化为人体系统，并利用它 改进体外分化方案的知识。

项目成果

Enhanced differentiation of human induced pluripotent stem cells toward the midbrain dopaminergic neuron lineage through GLYPICAN-4 downregulation.

通过 GLYPICAN-4 下调增强人诱导多能干细胞向中脑多巴胺能神经元谱系的分化。

• 发表时间: 2021
• 影响因子: 6
• 作者: Corti, Serena;Bonjean, Remi;Legier, Thomas;Rattier, Diane;Melon, Christophe;Salin, Pascal;Toso, Erik A;Kyba, Michael;Kerkerian;Maina, Flavio;Dono, Rosanna
• 通讯作者: Dono, Rosanna