Skeletal Muscle Stem Cells Derived from Teratomas

来自畸胎瘤的骨骼肌干细胞

• 批准号: 9919497
• 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/9919497
• 关键词: Address; Advanced Development; Cell Differentiation process; Cell Therapy; Cells; Data; Development; Environment; 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; Protocols documentation; Public Health; Regenerative Medicine; Risk; Series; Signal Transduction; Signaling Protein; Skeletal Development; Skeletal Muscle; Surface; System; Teratoma; Time; Tissues; Translating; Transplantation; base; human pluripotent stem cell; improved; in vivo; in vivo regeneration; induced pluripotent stem cell; insight; muscle regeneration; muscle transplantation; novel; progenitor; regenerative; 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.

摘要