Bio-Engineered Mesenchymal Stromal Cell (MSCs) Grafts for Skin Repair/Regeneration. Preclinical Aspects

There are growing evidence showing the promise of mesenchymal stromal cells (MSCs) for the treatment of cutaneous wound healing. In a previous study we have demonstrated that MSCs seeded on artificial dermal matrix, Integra enriched with platelet rich plasma (PRP) has enhanced proliferative attitude as compared to those cultured on the scaffold alone. In this study we wanted to extend the experimentation by evaluating the efficacy of the bioengineered cellular and acellular scaffold in a vivo model of skin damage in rats. To this purpose, we used MSCs derived genetic modified rats overexpressing Green fluorescent protein (GFP). Rats were divided into different groups: those receiving Integra or Ematrix, Integra plus MSC; Ematrix plus MSC and injured untreated control. Of interest, the presence of MSCs within the scaffolds accelerated wound closure and greatly ameliorated the quality of regenerated skin which showed reduced collagen deposition, enhanced re-epithelization, increased neo-angiogenesis and greater return of hair follicles and sebaceous glands. No evidence of MSCs transdifferentiation in the wound was observed suggesting that this therapeutic were likely due to MSC releasing paracrine factors that regulated the local cellular response to cutaneous injury. Moreover, MSCs enhanced the recruitment of the endogenous epithelial precursors to the sites of injry, allowing to speculate that transplanted MSCs may contribute to the recreation of a suitable microenvironment that stimulate adult keratinocyte stemness, a condition indispensable to improve skin regeneration. In conclusion, the results of this study provide strong evidence that transplantation with MSCs seeded on suitable biological scaffolds constitute a therapeutic strategy for the treatment of skin injury.