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Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation [RNA-seq]

ABSTRACT: Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation [RNA-seq]

PROVIDER: PRJNA888141 | ENA |

REPOSITORIES: ENA

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Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation

Project description:Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation

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Project description:Satellite cells, the stem cells of skeletal muscle tissue, hold a remarkable regeneration capacity and therapeutic potential in regenerative medicine. However, low satellite cell yield from autologous or donor-derived muscles hinders the adoption of satellite cell transplantation for the treatment of muscle diseases, including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether satellite cells can be derived in allogeneic or xenogeneic animal hosts. First, injection of CRISPR/Cas9-corrected mouse DMD-induced pluripotent stem cells (iPSCs) into mouse blastocysts carrying an ablation system of host satellite cells gave rise to intraspecies chimeras exclusively carrying iPSC-derived satellite cells. Furthermore, injection of genetically corrected DMD-iPSCs into rat blastocysts resulted in the formation of interspecies rat-mouse chimeras harboring mouse satellite cells. Remarkably, iPSC-derived satellite cells or derivative myoblasts produced in intraspecies or interspecies chimeras restored dystrophin expression in DMD mice following intramuscular transplantation, and contributed to the satellite cell pool. Collectively, this study demonstrates the feasibility of producing therapeutically competent stem cells across divergent animal species, raising the possibility of generating human muscle stem cells in large animals for regenerative medicine purposes.

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Xenogeneic Skin Transplantation Promotes Angiogenesis and Tissue Regeneration

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An FGF-2 signaling pathway that is activated in aged skeletal muscle promotes intramuscular adipogenesis

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