Harnessingnerve-musclecell interactions for biomaterials-based skeletal muscle regeneration
Harnessingnerve-musclecell interactions for biomaterials-based skeletal muscle regeneration
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DOI：
10.1002/jbm.a.37022
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发表时间：
2020-06-26
影响因子：
4.9
通讯作者：
Deng, Meng
中科院分区：
文献类型：
--
作者：
Narayanan, Naagarajan;Lengemann, Paul;Deng, Meng
神经细胞分泌神经营养因子，对神经元的存活、增殖和再生起关键作用。然而，它们在调节成肌细胞行为和骨骼肌修复中的作用在很大程度上仍未被探索。在本研究中，我们研究了PC12分泌的信号因子在生理相关条件下调节C2C12成肌细胞行为的作用。在2D培养和3D电纺纤维支架体系中，PC12条件培养液均以剂量依赖的方式调节成肌细胞的增殖和分化。我们进一步开发了一种仿生的、可调的水凝胶，由透明质酸、硫酸软骨素和聚乙二醇组成，作为包裹PC12细胞的3D基质。水凝胶包裹的PC12细胞在共培养中促进成肌细胞的存活和增殖。进一步的蛋白质组学分析从包裹的PC12细胞的分泌体中鉴定出总共2,088个蛋白质，并揭示了神经分泌蛋白质在骨骼肌再生中的生物学作用和重叠功能，可能是通过调节成肌细胞的行为、神经功能和血管生成。这些实验提供了对神经-肌肉相互作用的见解，并为开发先进的生物材料策略铺平了道路，该策略将神经细胞分泌组结合起来加速骨骼肌再生。
Nerve cells secrete neurotrophic factors that play a critical role in neuronal survival, proliferation, and regeneration. However, their role in regulating myoblast behavior and skeletal muscle repair remains largely unexplored. In the present study, we investigated the effects of PC12 secreted signaling factors in modulating C2C12 myoblast behavior under physiologically relevant conditions. We showed that PC12 conditioned media modulated myoblast proliferation and differentiation in both 2D culture and 3D aligned electrospun fiber scaffold system in a dose-dependent manner. We further developed a biomimetic, tunable hydrogel consisting of hyaluronic acid, chondroitin sulfate, and polyethylene glycol as a 3D matrix encapsulating PC12 cells. The hydrogel-encapsulated PC12 cells promoted survival and proliferation of myoblasts in co-culture. Further proteomics analysis identified a total of 2,088 proteins from the secretome of the encapsulated PC12 cells and revealed the biological role and overlapping functions of nerve-secreted proteins for skeletal muscle regeneration, potentially through regulating myoblast behavior, nerve function, and angiogenesis. These experiments provide insights into the nerve-muscle interactions and pave the way for developing advanced biomaterials strategies incorporating nerve cell secretome for accelerated skeletal muscle regeneration.