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Development and application of human skeletal muscle microphysiological systems
Lab on a Chip ( IF 6.1 ) Pub Date : 2018-08-28 00:00:00 , DOI: 10.1039/c8lc00553b
George A Truskey 1
Affiliation  

A number of major disease states involve skeletal muscle, including type 2 diabetes, muscular dystrophy, sarcopenia and cachexia arising from cancer or heart disease. Animals do not accurately represent many of these disease states. Human skeletal muscle microphysiological systems derived from primary or induced pluripotent stem cells (hPSCs) can provide an in vitro model of genetic and chronic diseases and assess individual variations. Three-dimensional culture systems more accurately represent skeletal muscle function than do two-dimensional cultures. While muscle biopsies enable culture of primary muscle cells, hPSCs provide the opportunity to sample a wider population of donors. Recent advances to promote maturation of PSC-derived skeletal muscle provide an alternative to primary cells. While contractile function is often measured in three-dimensional cultures and several systems exist to characterize contraction of small numbers of muscle fibers, there is a need for functional measures of metabolism suited for microphysiological systems. Future research should address generation of well-differentiated hPSC-derived muscle cells, enabling muscle repair in vitro, and improved disease models.

中文翻译:


人体骨骼肌微生理系统的开发与应用



许多主要疾病状态都涉及骨骼肌,包括 2 型糖尿病、肌营养不良、肌肉减少症和癌症或心脏病引起的恶病质。动物并不能准确地代表许多这些疾病状态。源自原代或诱导多能干细胞 (hPSC) 的人类骨骼肌微生理系统可以提供遗传和慢性疾病的体外模型并评估个体差异。三维培养系统比二维培养系统更准确地代表骨骼肌功能。虽然肌肉活检可以培养原代肌肉细胞,但 hPSC 提供了对更广泛的供体群体进行采样的机会。促进 PSC 衍生骨骼肌成熟的最新进展提供了原代细胞的替代方案。虽然收缩功能通常在三维培养物中测量,并且存在多个系统来表征少量肌纤维的收缩,但需要适合微生理系统的代谢功能测量。未来的研究应该解决分化良好的 hPSC 衍生肌肉细胞的产生问题,从而实现体外肌肉修复,并改进疾病模型。
更新日期:2018-08-28
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