Microphysiological system for studying contractile differences in young, active, and old, sedentary adult derived skeletal muscle cells.
Microphysiological system for studying contractile differences in young, active, and old, sedentary adult derived skeletal muscle cells.
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研究年轻、活跃和年老、静止的成人骨骼肌细胞收缩差异的微生理学系统。
作者：
微生理系统（MPS），也称为组织芯片，结合3D骨骼肌束是一种新的方法，用于生理和药理学研究，以发现新的药物治疗肌肉减少症。我们描述了一种MPS，其中来自供体特异性卫星细胞的工程化骨骼肌肌束（模拟老化表型）被封装在含有铂电极的灌注组织芯片平台中。我们的肌束来源于CD 56+肌源性细胞，这些细胞是通过经皮穿刺股外侧肌获得的，这些肌源性细胞是根据年龄和体力活动进行表型分型的成年人。经过17天的分化，包括5天的3V，2 Hz电刺激方案，肌束表现出融合的肌管排列和肌原性，肌纤维组装，信号和收缩基因的上调，如通过基因阵列分析和定位肌节的关键组分所证明的。我们的研究结果表明，来自年轻活跃（YA）组的肌束显示出高强度的α辅肌动蛋白免疫荧光染色，与未受刺激的肌束相比，对电刺激的位移幅度约为1 μm。来自老年久坐组（OS）的肌束没有显示出同步收缩反应。与OS衍生的肌束相比，YA衍生的肌束对刺激的响应增加，如胰岛素生长因子（IGF-1）、α辅肌动蛋白（ACTN 3、ACTA 1）和快缩肌钙蛋白（TNNI 2）的上调所示。我们的MPS模拟肌肉衰退的疾病状态，因此提供了一个老化的系统和实验平台来研究模拟运动方案的电刺激，并且可以适用于针对肌肉减少症的治疗评价的化合物功效和毒性的长期研究。使用三维微生理系统D MPS研究骨骼肌对电刺激反应的年龄相关差异的新平台，该系统包含来自以年龄和身体活动为特征的良好表型成人的细胞。
Microphysiological systems (MPS), also referred to as tissue chips, incorporating 3D skeletal myobundles are a novel approach for physiological and pharmacological studies to uncover new medical treatments for sarcopenia. We characterize a MPS in which engineered skeletal muscle myobundles derived from donor‐specific satellite cells that model aged phenotypes are encapsulated in a perfused tissue chip platform containing platinum electrodes. Our myobundles were derived from CD56+ myogenic cells obtained via percutaneous biopsy of the vastus lateralis from adults phenotyped by age and physical activity. Following 17 days differentiation including 5 days of a 3 V, 2 Hz electrical stimulation regime, the myobundles exhibited fused myotube alignment and upregulation of myogenic, myofiber assembly, signaling and contractile genes as demonstrated by gene array profiling and localization of key components of the sarcomere. Our results demonstrate that myobundles derived from the young, active (YA) group showed high intensity immunofluorescent staining of α‐actinin proteins and responded to electrical stimuli with a ~1 μm displacement magnitude compared with non‐stimulated myobundles. Myobundles derived from older sedentary group (OS) did not display a synchronous contraction response. Hypertrophic potential is increased in YA‐derived myobundles in response to stimulation as shown by upregulation of insulin growth factor (IGF‐1), α‐actinin (ACTN3, ACTA1) and fast twitch troponin protein (TNNI2) compared with OS‐derived myobundles. Our MPS mimics disease states of muscle decline and thus provides an aged system and experimental platform to investigate electrical stimulation mimicking exercise regimes and may be adapted to long duration studies of compound efficacy and toxicity for therapeutic evaluation against sarcopenia. Novel platform to study age‐related differences in skeletal muscle response to electrical stimulation using a 3 dimensional microphysiological system D MPS that incorporates cells derived from well phenotyped adults characterized by age and physical activity.
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影响因子：
3.6
作者：
Aas V;Thoresen GH;Rustan AC;Lund J
通讯作者：
Lund J
影响因子：
6.6
作者：
Guo, Xiufang;Greene, Keshel;Hickman, James J.
通讯作者：
Hickman, James J.
影响因子：
3.4
作者：
Mars, Tomaz;Mis, Katarina;Nikolic, Natasa
通讯作者：
Nikolic, Natasa
DOI：
10.1002/jcsm.12272
发表时间：
2018-04
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Distefano G;Standley RA;Zhang X;Carnero EA;Yi F;Cornnell HH;Coen PM
通讯作者：
Coen PM
影响因子：
3
作者：
Lund, Jenny;Tangen, Daniel S.;Jensen, Jorgen
通讯作者：
Jensen, Jorgen