The persistence of activated myofibroblasts is a hallmark of fibrosis of many organs. Thus, the modulation of the generation/functionality of these cells may represent a strategical anti-fibrotic therapeutic option. Bone marrow-derived mesenchymal stromal cell (MSC)-based therapy has shown promising clues, but some criticisms still limit the clinical use of these cells, including the need to avoid xenogeneic compound contamination for ex vivo cell amplification and the identification of appropriate growth factors acting as a pre-conditioning agent and/or cell delivery vehicle during transplantation, thus enabling the improvement of cell survival in the host tissue microenvironment. Many studies have demonstrated the ability of platelet-rich plasma (PRP), a source of many biologically active molecules, to positively influence MSC proliferation, survival, and functionality, as well as its anti-fibrotic potential. Here we investigated the effects of PRP, murine and human bone marrow-derived MSCs, and of the combined treatment PRP/MSCs on in vitro differentiation of murine NIH/3T3 and human HDFα fibroblasts to myofibroblasts induced by transforming growth factor (TGF)-β1, a well-known pro-fibrotic agent. The myofibroblastic phenotype was evaluated morphologically (cell shape and actin cytoskeleton assembly) and immunocytochemically (vinculin-rich focal adhesion clustering, α-smooth muscle actin and type-1 collagen expression). We found that PRP and MSCs, both as single treatments and in combination, were able to prevent the TGF-β1-induced fibroblast-myofibroblast transition. Unexpectedly, the combination PRP/MSCs had no synergistic effects. In conclusion, within the limitations related to an in vitro experimentation, our study may contribute to providing an experimental background for supporting the anti-fibrotic potential of the combination PRP/MSCs which, once translated “from bench to bedside,” could potentially offer advantages over the single treatments.

中文翻译：

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富含血小板的血浆和骨髓源性间充质基质细胞可防止 TGF-β1 诱导的肌成纤维细胞生成，但组合时不协同：形态学体外分析

活化的肌成纤维细胞的持续存在是许多器官纤维化的标志。因此，这些细胞的产生/功能的调节可能代表了一种战略性的抗纤维化治疗选择。基于骨髓间充质基质细胞 (MSC) 的疗法已显示出有希望的线索，但一些批评仍然限制了这些细胞的临床应用，包括需要避免异种化合物污染以进行体外细胞扩增和确定合适的生长因子在移植过程中充当预处理剂和/或细胞递送载体，从而能够改善宿主组织微环境中的细胞存活率。许多研究表明，富含血小板的血浆 (PRP)（许多生物活性分子的来源）具有积极影响 MSC 增殖的能力，生存和功能，以及其抗纤维化潜力。在这里，我们研究了 PRP、鼠和人骨髓来源的 MSC 以及联合治疗 PRP/MSC 对由转化生长因子 (TGF)-β1 诱导的鼠 NIH/3T3 和人 HDFα 成纤维细胞向肌成纤维细胞的体外分化的影响，一种众所周知的促纤维化剂。通过形态学（细胞形状和肌动蛋白细胞骨架组装）和免疫细胞化学（富含纽蛋白的粘着斑聚集、α-平滑肌肌动蛋白和 1 型胶原表达）评估肌成纤维细胞表型。我们发现 PRP 和 MSCs，无论是作为单一治疗还是联合治疗，都能够阻止 TGF-β1 诱导的成纤维细胞 - 肌成纤维细胞转变。出乎意料的是，PRP/MSCs 的组合没有协同作用。综上所述，