Wound Healing and Differentiation Potential among Human Vascular Wall Mesenchymal Stem Cells, Dermal Fibroblast and Myofibroblast Cell Lines

Abstract

Lower-limb ulcers represent a debilitating phenomenon with a prevalence of 3% in the people over 65 years old. The ulcers are particularly severe in diabetic patients where they tend to become chronic non-healing wounds, leading to a series of clinical complications. Nowadays, although surgical revascularization remains the gold standard therapeutical option for wound healing, many new therapeutic approaches are under development to facilitate and accelerate the recovery of the injured tissues. In this context, the use of growth factors, mesenchymal stem cells and autologous fibroblasts are acquiring increasingly importance. Based on these evidences, this study was aimed to test one of the proangiogenic factors, HGF, on hVW-MSCs isolated from human arteries and compare the differentiation potential between hVW-MSC and the stromal counterpart (dermal fibroblasts and myofibroblasts).HGF effect on hVW-MSCs was studied; proliferation, migration, motility, angiogenic induction and modulation of tissue remodeling and inflammation markers were specific areas investigated. HGF was also tested on MSCs recovered from abdominal aortic aneurysms (AAA-MSCs). Furthermore, assays of angiogenic and adipogenic differentiation potential were established on hVW-MSCs, dermal fibroblasts and myofibroblasts.HGF stimulates migration, motility and angiogenic differentiation of hVW-MSCs, but it has no effect on proliferation and tissue remodeling and inflammation markers. Results on AAA-MSCs show that HGF decreases the expression of inflammatory cytokines and positively modulate some markers involved in tissue remodeling. Finally, hVW-MSCs own a higher angiogenic and adipogenic commitment compared to dermal fibroblasts and myofibroblasts.The combined use of HGF and hVW-MSCs, especially because of their high differentiation potential, represents a promising therapeutic strategy, in order to facilitate the healing of unresponsive vascular ulcers.