Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Tissue Eng Part A. 2020 Feb;26(3-4):167-177. doi: 10.1089/ten.TEA.2019.0087. Epub 2019 Oct 7.
Volumetric muscle loss (VML) contributes to the number of soft tissue injuries that necessitate reconstructive surgery, but treatment options are often limited by tissue availability and donor site morbidity. To combat these issues, our laboratory has developed scaffold-free tissue-engineered skeletal muscle units (SMUs) as a novel treatment for VML injuries. Recently, we have begun experiments addressing VML in facial muscle, and the optimal starting cell population for engineered skeletal muscle tissue for this application may not be cells derived from hindlimb muscles due to reported heterogeneity of cell populations. Thus, the purpose of this study was to compare SMUs fabricated from both craniofacial and hindlimb sources to determine which cell source is best suited for the engineering of skeletal muscle. Herein, we assessed the development, structure, and function of SMUs derived from four muscle sources, including two hindlimb muscles (i.e., soleus and semimembranosus [SM]) and two craniofacial muscles (i.e., zygomaticus major and masseter). Overall, the zygomaticus major exhibited the least efficient digestion, and SMUs fabricated from this muscle exhibited the least aligned myosin heavy chain staining and consequently, the lowest average force production. Conversely, the SM muscle exhibited the most efficient digestion and the highest number of myotubes/mm; however, the SM, masseter, and soleus groups were roughly equivalent in terms of force production and histological structure. Impact Statement An empirical comparison of the development, structure, and function of engineered skeletal muscle tissue fabricated from different muscles, including both craniofacial and hindlimb sources, will not only provide insight into innate regenerative mechanisms of skeletal muscle but also will give our team and other researchers the information necessary to determine which cell sources are best suited for the skeletal muscle tissue engineering.
体积性肌肉损失（VML）导致需要进行重建手术的软组织损伤数量增加，但治疗选择通常受到组织可用性和供体部位发病率的限制。为了解决这些问题，我们的实验室已经开发了无支架组织工程化骨骼肌单位（SMU）作为 VML 损伤的一种新的治疗方法。最近，我们已经开始进行面部肌肉的 VML 实验，由于报道的细胞群体异质性，对于这种应用，用于工程化骨骼肌组织的最佳起始细胞群体可能不是来自后肢肌肉的细胞。因此，本研究的目的是比较来自颅面和后肢来源的 SMU，以确定哪种细胞来源最适合工程化骨骼肌。在此，我们评估了源自四个肌肉来源的 SMU 的发育、结构和功能，包括两个后肢肌肉（即比目鱼肌和半膜肌）和两个颅面肌肉（即颧大肌和咬肌）。总体而言，颧大肌的消化效率最低，由此制造的 SMU 表现出最少的肌球蛋白重链染色对齐，因此平均产生的力最低。相反，SM 肌肉表现出最高的消化效率和最高的肌管数/mm；然而，SM、咬肌和比目鱼肌组在产生力和组织学结构方面大致相当。影响说明对源自不同肌肉（包括颅面和后肢来源）的工程化骨骼肌组织的发育、结构和功能进行实证比较，不仅将深入了解骨骼肌的固有再生机制，还将为我们的团队和其他研究人员提供必要的信息，以确定哪种细胞来源最适合骨骼肌组织工程。
