MSC Forming Microvasculature for Wound Healing

The wound healing process is a complex series of events and its impairment, as in the case of non-healing, chronic wounds which are a common occurrence associated with vascular disease, may stem from insufficient angiogenesis in affected sites. We have developed a stiff, high-concentration fibrin formulation that allows adipose-derived mesenchymal stromal cells (ADSCs) to form tubular structures in vitro. The tubular structures express markers of endothelium, including CD31 and VE-Cadherin, as well as the pericyte marker NG2 and give rise to perfusable vessels that are VE-cadherin positive after subcutaneous injection into mice.

The application of ADSCs delivered in the stiff fibrin gels to a mouse model of wound healing also allowed for wounds to heal more quickly, as assessed by wound size, amount of granulation tissue and collagen content. Interestingly, ADSCs remain within the fibrin gel and do not integrate into the granulation tissue of healing wounds in vivo. ADSCs are able to form tubular structures within fibrin gels, and may also contribute to faster wound healing, as compared with no treatment or to wounds treated with fibrin gels devoid of ADSCs.