Engineering human pluripotent stem cells into a functional skeletal muscle tissue.
Engineering human pluripotent stem cells into a functional skeletal muscle tissue.
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DOI：
10.1038/s41467-017-02636-4
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发表时间：
2018-01-09
影响因子：
16.6
通讯作者：
Bursac N
中科院分区：
文献类型：
--
作者：
Rao L;Qian Y;Khodabukus A;Ribar T;Bursac N
利用人类多能干细胞（hPSC）生成功能性骨骼肌组织尚未见报道。在这里，我们通过在 hPSC 分化的近轴中胚层细胞中短暂过度表达 Pax7 来衍生诱导性肌源性祖细胞 (iMPC)。在 2D 培养中，iMPC 很容易分化成自发收缩的多核肌管和内源表达 Pax7 的卫星样细胞池。在优化的 3D 培养条件下，源自多个 hPSC 系的 iMPC 可重复地形成功能性骨骼肌组织（iSKM 束），其中包含对齐的多核肌管，这些肌管在电或乙酰胆碱刺激下表现出正的力-频率关系和强大的钙瞬变。在 1 个月的培养过程中，iSKM 束经历了结构和分子成熟、肥大和力量产生的增加。当植入免疫功能低下小鼠的背窗室或后肢肌肉时，iSKM 束会存活下来，逐渐血管化并维持功能。 iSKM 捆绑包有望成为人类肌肉疾病建模和药物开发的微生理学平台。从人类多能干细胞产生功能性骨骼肌组织尚未见报道。在这里，作者描述了培养物中收缩性骨骼肌束的工程设计，这些肌束在移植到小鼠体内时会变得血管化并保持功能。
The generation of functional skeletal muscle tissues from human pluripotent stem cells (hPSCs) has not been reported. Here, we derive induced myogenic progenitor cells (iMPCs) via transient overexpression of Pax7 in paraxial mesoderm cells differentiated from hPSCs. In 2D culture, iMPCs readily differentiate into spontaneously contracting multinucleated myotubes and a pool of satellite-like cells endogenously expressing Pax7. Under optimized 3D culture conditions, iMPCs derived from multiple hPSC lines reproducibly form functional skeletal muscle tissues (iSKM bundles) containing aligned multi-nucleated myotubes that exhibit positive force–frequency relationship and robust calcium transients in response to electrical or acetylcholine stimulation. During 1-month culture, the iSKM bundles undergo increased structural and molecular maturation, hypertrophy, and force generation. When implanted into dorsal window chamber or hindlimb muscle in immunocompromised mice, the iSKM bundles survive, progressively vascularize, and maintain functionality. iSKM bundles hold promise as a microphysiological platform for human muscle disease modeling and drug development. The generation of functional skeletal muscle tissue from human pluripotent stem cells has not been reported. Here, the authors describe engineering of contractile skeletal muscle bundles in culture, which become vascularized and maintain functionality when transplanted into mice.
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影响因子：
2.7
作者：
Day, Kenneth;Shefer, Gabi;Yablonka-Reuveni, Zipora
通讯作者：
Yablonka-Reuveni, Zipora
影响因子：
6
作者：
Abujarour, Ramzey;Bennett, Monica;Flynn, Peter
通讯作者：
Flynn, Peter
DOI：
10.1126/science.1191035
发表时间：
2010-08-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert PM;Havenstrite KL;Magnusson KE;Sacco A;Leonardi NA;Kraft P;Nguyen NK;Thrun S;Lutolf MP;Blau HM
通讯作者：
Blau HM
DOI：
10.1042/cs0520283
发表时间：
1977-01-01
期刊：
CLINICAL SCIENCE AND MOLECULAR MEDICINE
影响因子：
--
作者：
EDWARDS, RHT;YOUNG, A;JONES, DA
通讯作者：
JONES, DA
影响因子：
14.8
作者：
Chal, Jerome;Al Tanoury, Ziad;Pourquie, Olivier
通讯作者：
Pourquie, Olivier