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In Vitro Tissue‐Engineered Skeletal Muscle Models for Studying Muscle Physiology and Disease
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2018-04-25 , DOI: 10.1002/adhm.201701498 Alastair Khodabukus 1 , Neel Prabhu 1 , Jason Wang 1 , Nenad Bursac 1
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2018-04-25 , DOI: 10.1002/adhm.201701498 Alastair Khodabukus 1 , Neel Prabhu 1 , Jason Wang 1 , Nenad Bursac 1
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Healthy skeletal muscle possesses the extraordinary ability to regenerate in response to small‐scale injuries; however, this self‐repair capacity becomes overwhelmed with aging, genetic myopathies, and large muscle loss. The failure of small animal models to accurately replicate human muscle disease, injury and to predict clinically‐relevant drug responses has driven the development of high fidelity in vitro skeletal muscle models. Herein, the progress made and challenges ahead in engineering biomimetic human skeletal muscle tissues that can recapitulate muscle development, genetic diseases, regeneration, and drug response is discussed. Bioengineering approaches used to improve engineered muscle structure and function as well as the functionality of satellite cells to allow modeling muscle regeneration in vitro are also highlighted. Next, a historical overview on the generation of skeletal muscle cells and tissues from human pluripotent stem cells, and a discussion on the potential of these approaches to model and treat genetic diseases such as Duchenne muscular dystrophy, is provided. Finally, the need to integrate multiorgan microphysiological systems to generate improved drug discovery technologies with the potential to complement or supersede current preclinical animal models of muscle disease is described.
中文翻译：
用于研究肌肉生理学和疾病的体外组织工程骨骼肌模型
健康的骨骼肌具有非凡的再生能力，可以应对小规模的损伤；然而，这种自我修复能力会因衰老、遗传性肌病和大量肌肉损失而不堪重负。小动物模型无法准确复制人类肌肉疾病、损伤以及预测临床相关药物反应，这推动了高保真体外骨骼肌模型的发展。本文讨论了工程仿生人类骨骼肌组织所取得的进展和面临的挑战，该组织可以重现肌肉发育、遗传疾病、再生和药物反应。还强调了用于改善工程肌肉结构和功能以及卫星细胞功能以允许体外肌肉再生建模的生物工程方法。接下来，提供了人类多能干细胞生成骨骼肌细胞和组织的历史概述，并讨论了这些方法模拟和治疗杜氏肌营养不良症等遗传性疾病的潜力。最后，描述了整合多器官微生理系统以产生改进的药物发现技术的需要，该技术有可能补充或取代当前的肌肉疾病临床前动物模型。
更新日期：2018-04-25
中文翻译：
用于研究肌肉生理学和疾病的体外组织工程骨骼肌模型
健康的骨骼肌具有非凡的再生能力，可以应对小规模的损伤；然而，这种自我修复能力会因衰老、遗传性肌病和大量肌肉损失而不堪重负。小动物模型无法准确复制人类肌肉疾病、损伤以及预测临床相关药物反应，这推动了高保真体外骨骼肌模型的发展。本文讨论了工程仿生人类骨骼肌组织所取得的进展和面临的挑战，该组织可以重现肌肉发育、遗传疾病、再生和药物反应。还强调了用于改善工程肌肉结构和功能以及卫星细胞功能以允许体外肌肉再生建模的生物工程方法。接下来，提供了人类多能干细胞生成骨骼肌细胞和组织的历史概述，并讨论了这些方法模拟和治疗杜氏肌营养不良症等遗传性疾病的潜力。最后，描述了整合多器官微生理系统以产生改进的药物发现技术的需要，该技术有可能补充或取代当前的肌肉疾病临床前动物模型。
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