Diabetic Conditions Confer Metabolic and Structural Modifications to Tissue-Engineered Skeletal Muscle
Diabetic Conditions Confer Metabolic and Structural Modifications to Tissue-Engineered Skeletal Muscle
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DOI：
10.1089/ten.tea.2020.0138
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发表时间：
2020-10-06
影响因子：
4.1
通讯作者：
Rathbone, Christopher R.
中科院分区：
文献类型：
--
作者：
Acosta, Francisca M.;Jia, U-Ter Aonda;Rathbone, Christopher R.
骨骼肌是一种直接参与2型糖尿病（T2 D）进展和持续的组织，这种疾病正变得越来越常见。更好地了解在T2 D背景下影响骨骼肌功能障碍的机制有可能为大量患者带来新的治疗方法。通过其模仿骨骼肌结构的能力，同时也结合疾病的方面，组织工程化骨骼肌（TE-SkM）有可能提供一种快速高通量发现治疗骨骼肌功能障碍的方法，包括T2 D发生的方法。从瘦或肥胖的雄性Zucker糖尿病肥胖大鼠分离的肌肉前体细胞用于产生TE-SkM构建体。用脂肪形成诱导培养基处理一些构建体以强调脂肪细胞的存在，这是T2 D骨骼肌的特征性特征。成熟度（压实和肌酸激酶活性），机械完整性（杨氏模量），组织（肌管方向），和代谢能力（胰岛素刺激的葡萄糖摄取）都降低了糖尿病。用成脂诱导培养基处理构建体增加了糖尿病TE-SkM构建体内的脂质量，并引起了瘦和糖尿病样品中构建体压实、细胞取向和胰岛素刺激的葡萄糖摄取的变化。总的来说，本文的研究结果表明，T2 D的结构和代谢方面的重演可以通过体外工程化骨骼肌来完成。影响声明骨骼肌的组织工程模型疾病和损伤有很大的希望提供一种工具，以开发和/或改善治疗方法，改善医疗保健。2型糖尿病是一种最常见的致衰性疾病，其组织工程化骨骼肌模型已经在体外开发，其结构和代谢改变与体内疾病表型一致。
Skeletal muscle is a tissue that is directly involved in the progression and persistence of type 2 diabetes (T2D), a disease that is becoming increasingly common. Gaining better insight into the mechanisms that are affecting skeletal muscle dysfunction in the context of T2D has the potential to lead to novel treatments for a large number of patients. Through its ability to emulate skeletal muscle architecture while also incorporating aspects of disease, tissue-engineered skeletal muscle (TE-SkM) has the potential to provide a means for rapid high-throughput discovery of therapies to treat skeletal muscle dysfunction, to include that which occurs with T2D. Muscle precursor cells isolated from lean or obese male Zucker diabetic fatty rats were used to generate TE-SkM constructs. Some constructs were treated with adipogenic induction media to accentuate the presence of adipocytes that is a characteristic feature of T2D skeletal muscle. The maturity (compaction and creatine kinase activity), mechanical integrity (Young's modulus), organization (myotube orientation), and metabolic capacity (insulin-stimulated glucose uptake) were all reduced by diabetes. Treating constructs with adipogenic induction media increased the quantity of lipid within the diabetic TE-SkM constructs, and caused changes in construct compaction, cell orientation, and insulin-stimulated glucose uptake in both lean and diabetic samples. Collectively, the findings herein suggest that the recapitulation of structural and metabolic aspects of T2D can be accomplished by engineering skeletal musclein vitro. Impact Statement The tissue engineering of skeletal muscle to model disease and injury has great promise to provide a tool to develop and/or improve therapeutic approaches for improved health care. A tissue-engineered skeletal muscle model of one of the most common and debilitating diseases, type 2 diabetes, has been developedin vitroas evidenced by the structural and metabolic alterations that are consistent with the disease phenotypein vivo.