Evaluation of Mesenchymal Stem Cell Angiogenic Capacity Driven by Wnt3a for Enhanced Wound Healing

Abstract

It has been acknowledged that the inferior viability of exogenous bone marrow-derived mesenchymal stem cells (BMSCs) may impede the clinical application of them for tissue engineering such as wound healing, in addition, how to enhance the angiogenic capacity of BMSCs for wound regeneration still remains a major challenge for surgeons. Wnt3a, a member of the classic canonical Wnt/β-signaling pathway, has been demonstrated to be able to regulate the balance of macrophage to make them acquire a pro-angiogenic phenotype, thus increasing the formation of new endothelial cells (ECs) for the further vascularization of wound. In this study we investigated a novel method by using the engraftment of exogenous BMSCs combined with Wnt3a to evaluate whether the strategy may enhance the viability of the stem cells and further promote wound healing. The in vitro culture of BMSCs with the presence of Wnt3a accompanied with the murine model with cutaneous wound treated with BMSC + Wnt3a were evaluated. The angiogenesis related markers including VEGF, NG2, α-SMA, CD31 were utilized to investigate whether the angiogenic capacity of BMSCs was promoted by Wnt3a. After 7 days culture with Wnt3a, stem cells showed direct differentiation into the vital cells that were required in angiogenesis related process. For in vivo test, murine wounds intervened by BMSCs coupled with Wnt3a showed enhanced vascularization featured as formation of blood vessels than did single BMSC engraftment or Wnt3a alone. More importantly, the representative markers of angiogenesis process (VEGF, NG2, α-SMA, CD31) were up-regulated in the animals managed with BMSCs coupled with Wnt3a. Overall, our results indicated that the combinatory therapy by using Wnt3a and BMSCs is capable of accelerating the wound healing via stimulating the angiogenic capacity of stem cells, thus enhancing the angiogenesis process within the wound.