RESULTS: Selective culture conditions yielded PAX3 and PAX7 positive skeletal muscle precursors from UiPSM cells. The skeletal muscle precursors undergo in vitro maturation resulting in myotube formation. MYOD effectively promoted the maturity of the skeletal myocytes in a short time. We found that UiPSM and MYOD mediated UiPSM cell-derived skeletal myocytes were viable after transplantation into the tibialis anterior muscle of MITRG mice, as assessed by bioluminescence imaging and scRNA-seq. Lack of teratoma formation and evidence of long-term myocytes engraftment suggests considerable potential for future therapeutic applications. Moreover, UiPSM cells can differentiate into osteoblast and chondroblast cells in vitro.
CONCLUSIONS: UiPSM differentiation has potential as a developmental model for musculoskeletal development research and treatment of musculoskeletal disorders.
结果:选择性培养条件从UiPSM细胞产生PAX3和PAX7阳性骨骼肌前体。骨骼肌前体经历体外成熟,导致肌管形成。MYOD在短时间内有效促进了骨骼肌细胞的成熟。我们发现UiPSM和MYOD介导的UiPSM细胞来源的骨骼肌细胞在移植到MITRG小鼠胫骨前肌后是有活力的,通过生物发光成像和scRNA-seq评估。缺乏畸胎瘤形成和长期肌细胞植入的证据表明,未来治疗应用的潜力很大。此外,UiPSM细胞可在体外分化为成骨细胞和成软骨细胞。
结论:UiPSM分化具有作为肌肉骨骼发育研究和治疗肌肉骨骼疾病的发育模型的潜力。