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Combined use of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and platelet rich plasma (PRP) stimulates proliferation and differentiation of myoblasts in vitro: new therapeutic perspectives for skeletal muscle repair/regeneration

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Abstract

Satellite cell-mediated skeletal muscle repair/regeneration is compromised in cases of extended damage. Bone marrow mesenchymal stromal cells (BM-MSCs) hold promise for muscle healing but some criticisms hamper their clinical application, including the need to avoid animal serum contamination for expansion and the scarce survival after transplant. In this context, platelet-rich plasma (PRP) could offer advantages. Here, we compare the effects of PRP or standard culture media on C2C12 myoblast, satellite cell and BM-MSC viability, survival, proliferation and myogenic differentiation and evaluate PRP/BM-MSC combination effects in promoting myogenic differentiation. PRP induced an increase of mitochondrial activity and Ki67 expression comparable or even greater than that elicited by standard media and promoted AKT signaling activation in myoblasts and BM-MSCs and Notch-1 pathway activation in BM-MSCs. It stimulated MyoD, myogenin, α-sarcomeric actin and MMP-2 expression in myoblasts and satellite cell activation. Notably, PRP/BM-MSC combination was more effective than PRP alone. We found that BM-MSCs influenced myoblast responses through a paracrine activation of AKT signaling, contributing to shed light on BM-MSC action mechanisms. Our results suggest that PRP represents a good serum substitute for BM-MSC manipulation in vitro and could be beneficial towards transplanted cells in vivo. Moreover, it might influence muscle resident progenitors’ fate, thus favoring the endogenous repair/regeneration mechanisms. Finally, within the limitations of an in vitro experimentation, this study provides an experimental background for considering the PRP/BM-MSC combination as a potential therapeutic tool for skeletal muscle damage, combining the beneficial effects of BM-MSCs and PRP on muscle tissue, while potentiating BM-MSC functionality.

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Acknowledgements

The authors are grateful to Dott. Benedetta Mazzanti (Department of Experimental and Clinical Medicine - Section of Hematology, University of Florence, Italy) for having kindly provided BM-MSCs and to Dott. Carlo Mirabella (Immunohaematology and Transfusion Medicine Unit of the University Hospital of Careggi, Florence, Italy) for PRP preparation.

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  1. Department of Experimental and Clinical Medicine - Section of Anatomy and Histology, University of Florence, Largo Brambilla 3, 50134, Florence, Italy

    Chiara Sassoli, Larissa Vallone, Alessia Tani, Flaminia Chellini, Daniele Nosi & Sandra Zecchi-Orlandini

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  1. Chiara Sassoli
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  2. Larissa Vallone
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  3. Alessia Tani
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  4. Flaminia Chellini
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  5. Daniele Nosi
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  6. Sandra Zecchi-Orlandini
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Correspondence to Chiara Sassoli.

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The authors declare that they have no conflict of interest.

Research involving human partecipants and/or animals-ethical approval

All procedures performed in studies involving animals were in accordance with the European Community guidelines for animal care (DL 116/92, application of the European Communities Council Directive of 24 November 1986; 86/609/EEC) and approved by the Committee for Animal Care and Experimental Use of the University of Florence - No. A5278–01. The protocols were communicated to local authorities and to the Italian Ministry of the Health; according to Italian law (Art.7/D.lgs 116/92) such a procedure does not require Ministry authorization. PRP was obtained at the Immunohaematology and Transfusion Medicine Unit of the University Hospital of Careggi (Florence) from the whole blood of adult healthy volunteers after receiving an informed consent and was provided in ready-to-use aliquots classified as not suitable for transfusion-infusion purposes. Its use in experimental in vitro protocols does not require Ethical Committee’s approval.

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Sassoli, C., Vallone, L., Tani, A. et al. Combined use of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and platelet rich plasma (PRP) stimulates proliferation and differentiation of myoblasts in vitro: new therapeutic perspectives for skeletal muscle repair/regeneration. Cell Tissue Res 372, 549–570 (2018). https://doi.org/10.1007/s00441-018-2792-3

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