Platelet-rich plasma and bone marrow derived-mesenchymal stromal cells prevent TGF-β1 induced myofibroblast generation but are not synergistic when combined: morphological in vitro analysis

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 compounds contamination for ex vivo cell amplification and the identification of appropriate growth factors acting as pre-conditioning agent and/or cell delivery vehicle during transplantation, thus enabling to improve cell survival in the host tissue microenvironment. Many studies 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. Myofibroblastic phenotype was evaluated morphologically (cell shape and actin cytoskeleton assembly) and immunocitochemically (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 provide experimental background for supporting the anti-fibrotic potential of the combination MSCs/PRP which, once translated “from bench to bedside”, could potentially offer advantages over the single treatments.