已知间充质基质/干细胞(MSC)及其分泌组在许多病理状态下发挥有益作用。然而,由于不合适的体外维持条件,MSC的治疗性质可能降低。标准培养方案忽略了这样一个事实,即MSC在体内存在与细胞外基质(ECM)最紧密的联系,复杂的蛋白质网络提供了一个有指导意义的微环境。我们最近发现,在细胞来源的脱细胞细胞外基质(CM-dECM)上培养的人子宫内膜MSCs的条件培养基中大量富含一些旁分泌因子,如GM-CSF,FGF-2,HGF,MMP-1,MCP-1,IL-6,IL-8,CXCL-1,-2,-5,-6(Ushakov等人。,2024).鉴于几种上调的分子属于已知参与骨骼肌再生的肌细胞,我们假设CM-dECM可能促进受损肌肉组织的恢复。这里,我们发现CM-dECM注射到氯化钡损伤的小鼠胫骨前肌中,导致肌纤维肥大并促进血管生成。此外,CM-dECM显着促进鼠C2C12成肌细胞细胞周期的进展,表明体内肌肉修复可能与刺激常驻成肌细胞增殖有关。在这项研究中,首先概述了在dECM上培养的子宫内膜MSCs的分泌组在损伤的鼠骨骼肌再生中的作用。我们的发现表明dECM上的培养可以被认为是增强MSC治疗潜力的新型预处理方法。
Mesenchymal stromal/stem cells (MSCs) and their secretome are known to exert beneficial effects in many pathological states. However, MSCs therapeutic properties can be reduced due to unsuitable in vitro maintenance conditions. Standard culture protocols neglect the fact that MSCs exist in vivo in the closest connection with the extracellular matrix (ECM), the complex protein network providing an instructive microenvironment. We found recently that conditioned medium from human endometrial MSCs cultured on cell-derived decellularized extracellular matrix (CM-dECM) is dramatically enriched in a number of paracrine factors such as GM-CSF, FGF-2, HGF, MMP-1, MCP-1, IL-6, IL-8, CXCL-1, -2, -5, -6 (Ushakov et al., 2024). Given that several upregulated molecules belong to myokines that are known to participate in skeletal muscle regeneration, we hypothesized that CM-dECM may promote restoration of damaged muscle tissue. Here, we found that CM-dECM injections into barium chloride-injured murine m. tibialis anterior caused myofiber hypertrophy and promoted angiogenesis. Besides, CM-dECM significantly contributed to progression of murine C2C12 myoblasts cell cycle suggesting that muscle repair in vivo may be connected with stimulation of resident myoblasts proliferation. In this study, a role for secretome of endometrial MSCs cultured on dECM in injured murine skeletal muscle regeneration was outlined first. Our findings demonstrate that culture on dECM may be considered as a novel preconditioning approach enhancing MSCs therapeutic potential.