Abstract

Adipose-derived stem cells (ASCs) are a promising therapeutic alternative for tissue repair in various clinical applications. However, restrictive cell survival, differential tissue integration, and undirected cell differentiation after transplantation in a hostile microenvironment are complications that require refinement. Plasma rich in growth factors (PRGF) from platelet-rich plasma favors human and canine ASC survival, proliferation, and delaying human ASC senescence and autophagocytosis in comparison with serum-containing cultures. In addition, canine and human-derived ASCs efficiently differentiate into osteocytes, adipocytes, or chondrocytes in the presence of PRGF. PRGF treatment induces phosphorylation of AKT preventing ASC death induced by lethal concentrations of hydrogen peroxide. Indeed, AKT inhibition abolished the PRGF apoptosis prevention in ASC exposed to 100 μM of hydrogen peroxide. Here, we show that canine ASCs respond to PRGF stimulus similarly to the human cells regarding cell survival and differentiation postulating the use of dogs as a suitable translational model. Overall, PRGF would be employed as a serum substitute for mesenchymal stem cell amplification to improve cell differentiation and as a preconditioning agent to prevent oxidative cell death.

Highlights

  • Adipose-derived stem cell (ASC) transplantation has already demonstrated effectiveness and continues to be an important avenue of research and development due to their extraordinary therapeutic aptitude

  • The experimental procedures for dogs did not require evaluation by the animal Ethics Committee because the procedure only included a cession of part of the amplified ASCs needed for cell transplantation, and for this purpose, the canine owners voluntarily signed an informed consent for the use of surplus adipose tissue utilized for the derivation of ASCs and further research purposes

  • Representative phase-contrast images of human ASCs in the presence of 10% human serum (HS) or plasma rich in growth factors (PRGF) are shown in Figure 1(a)

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Summary

Introduction

Adipose-derived stem cell (ASC) transplantation has already demonstrated effectiveness and continues to be an important avenue of research and development due to their extraordinary therapeutic aptitude. ASC activation with defined stimuli prior transplantation may enhance ASC repair capabilities and improve success rates for regenerative treatments. Recent studies have focused on increasing the yield, efficiency, and therapeutic capability of ASC by treating them with growth factors like PDGF or bFGF [6,7,8] or as a xenofree alternative for mesenchymal stem cell expansion [5, 9]. PRGF beneficial effects are modulated by the degranulation of alpha granules in platelets [12, 13] which contain

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