Platelet-Rich Plasma Improves the Wound Healing Potential of Mesenchymal Stem Cells through Paracrine and Metabolism Alterations

Abstract

Chronic and acute nonhealing wounds represent a major public health problem, and replacement of cutaneous lesions by the newly regenerated skin is challenging. Mesenchymal stem cells (MSC) and platelet-rich plasma (PRP) were separately tested in the attempt to regenerate the lost skin. However, these treatments often remained inefficient to achieve complete wound healing. Additional studies suggested that PRP could be used in combination with MSC to improve the cell therapy efficacy for tissue repair. However, systematic studies related to the effects of PRP on MSC properties and their ability to rebuild skin barrier are lacking. We evaluated in a mouse exhibiting 4 full-thickness wounds, the skin repair ability of a treatment combining human adipose-derived MSC and human PRP by comparison to treatment with saline solution, PRP alone, or MSC alone. Wound healing in these animals was measured at day 3, day 7, and day 10. In addition, we examined in vitro and in vivo whether PRP alters in MSC their proangiogenic properties, their survival, and their proliferation. We showed that PRP improved the efficacy of engrafted MSC to replace lost skin in mice by accelerating the wound healing processes and ameliorating the elasticity of the newly regenerated skin. In addition, we found that PRP treatment stimulated in vitro, in a dose-dependent manner, the proangiogenic potential of MSC through enhanced secretion of soluble factors like VEGF and SDF-1. Moreover, PRP treatment ameliorated the survival and activated the proliferation of in vitro cultured MSC and that these effects were accompanied by an alteration of the MSC energetic metabolism including oxygen consumption rate and mitochondrial ATP production. Similar observations were found in vivo following combined administration of PRP and MSC into mouse wounds. In conclusion, our study strengthens that the use of PRP in combination with MSC might be a safe alternative to aid wound healing.

Characterization of Naturally Occurring Bioactive Factor Mixtures for Bone Regeneration

“…Gabrielyan et al described a higher chemoattractive potential of HCM compared to pure VEGF (200 ng/mL), indicating the synergistic effects of the proteins in HCM [24]. Our results showed that proteins and cytokines are present in PL but not in HCM and ATE and stimulate cell proliferation, which is in line with the results from Herasant et al, who described an improved wound healing potential of MSCs in combination with platelet-rich plasma in mice [60].…”

Hopes and Limits of Adipose-Derived Stem Cells (ADSCs) and Mesenchymal Stem Cells (MSCs) in Wound Healing

“…Other investigations have used autologous or allogenic ADSCs in the treatment of Crohn's disease, critical limb ischemia, diabetic foot ulcers, and burns [63,[79][80][81][82]. In combination with fat or platelet-rich lysate, skin engraftment, and reconstitution have been improved in human and animal models [83][84][85]. Additionally, platelets lysate appeared to support ADSC proliferation and differentiation in vitro and might replace the use of fetal bovine serum during cell expansion [86].…”

Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020

“…In addition, the roles of individual cells that can be present in PRP treatment vials will be discussed along with detailed information on their effects on tissue regenerative processes. Furthermore, recent advances in understanding PRP bioformulations, platelet dosing, the specific roles of particular leukocytes, and the effects of PGF concentrations and cytokines on mesenchymal stem cell (MSC) trophic effects [ 10 ] will be described, including the pivotal roles of PRP in targeting different cells and tissue environments following cell-signaling and paracrine effects [ 11 ]. Likewise, we will discuss PRP mechanisms related to inflammation and angiogenesis in tissue repair and regenerative processes.…”