Bioengineered human skeletal muscle capable of functional regeneration.
Bioengineered human skeletal muscle capable of functional regeneration.
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DOI：
10.1186/s12915-020-00884-3
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发表时间：
2020-10-20
期刊：
影响因子：
5.4
通讯作者：
Lewis MP
中科院分区：
文献类型：
--
作者：
Fleming JW;Capel AJ;Rimington RP;Wheeler P;Leonard AN;Bishop NC;Davies OG;Lewis MP
骨骼肌（SkM）在受伤后再生，以高保真度替换受损组织。然而，在严重损伤中，非再生性缺陷使患者丧失功能，增加再损伤风险，并经常出现慢性疼痛。治疗这些非再生性缺陷的进展缓慢，只有在对再生有了全面了解的情况下才能取得进展。组织工程学已经允许开发在损伤后再生的SkM的生物工程模型，以支持再生生理学的研究。然而，迄今为止，还没有研究利用人肌源性前体细胞（hMPC）来密切模拟功能性人类再生生理学。在这里，我们解决了一些困难与细胞数量和hMPC促有丝分裂性使用磁联合细胞分选（MACS），标记CD 56，培养基补充成纤维细胞生长因子2（FGF-2）和B-27补充剂。细胞分选允许生肌细胞的延长扩增，并且补充显示出改善工程化组织内的肌生成和成熟时的力生成。此外，这些工程化的人SkM在氯化钡（BaCl 2）损伤后再生。损伤后，观察到功能（87.5%）和肌管数量（33.3%）减少，随后进入增殖期，MyoD+细胞增加，随后功能和肌管数量恢复。在整个恢复期观察到Pax 7+细胞群的扩增，表明在组织内产生Pax 7+细胞的能力，类似于体内观察到的卫星细胞的自我更新。这项工作概述了一种能够在损伤后进行功能性再生的工程化人类SkM，该系统建立在一个开源系统的基础上，添加到临床前测试工具箱中，以提高对基本再生生理学的理解。
Skeletal muscle (SkM) regenerates following injury, replacing damaged tissue with high fidelity. However, in serious injuries, non-regenerative defects leave patients with loss of function, increased re-injury risk and often chronic pain. Progress in treating these non-regenerative defects has been slow, with advances only occurring where a comprehensive understanding of regeneration has been gained. Tissue engineering has allowed the development of bioengineered models of SkM which regenerate following injury to support research in regenerative physiology. To date, however, no studies have utilised human myogenic precursor cells (hMPCs) to closely mimic functional human regenerative physiology. Here we address some of the difficulties associated with cell number and hMPC mitogenicity using magnetic association cell sorting (MACS), for the marker CD56, and media supplementation with fibroblast growth factor 2 (FGF-2) and B-27 supplement. Cell sorting allowed extended expansion of myogenic cells and supplementation was shown to improve myogenesis within engineered tissues and force generation at maturity. In addition, these engineered human SkM regenerated following barium chloride (BaCl2) injury. Following injury, reductions in function (87.5%) and myotube number (33.3%) were observed, followed by a proliferative phase with increased MyoD+ cells and a subsequent recovery of function and myotube number. An expansion of the Pax7+ cell population was observed across recovery suggesting an ability to generate Pax7+ cells within the tissue, similar to the self-renewal of satellite cells seen in vivo. This work outlines an engineered human SkM capable of functional regeneration following injury, built upon an open source system adding to the pre-clinical testing toolbox to improve the understanding of basic regenerative physiology.
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