Influence of growth factors and cytokines on angiogenic function of endothelial progenitor cells: a review of in vitro human studies

Growth factors and cytokines released at sites of injury and inflammation play an important role in stimulating endothelial progenitor cell (EPC) migration to these sites. A comparative analysis of the literature shows under neutral in vitro conditions (pH 7.4), several growth factors and cytokines influenced favorably indices of EPC angiogenic function. They included SDF-1, VEGF, PlGF, FGF-2, NGF and IL-1 beta. Others, e. g. TNF-alpha, have an unfavorable influence. SDF-1 and VEGF in combination increased chemotactic cell migration and reduced apoptosis caused by serum starvation. Under acidic conditions (pH 6.5), the biological activity of certain growth factors may be impaired, although TPO, SCF and IL-3 were each able to rescue EPCs from acidic exposure apoptosis, a combination of these three factors stimulated cell proliferation and prevented apoptosis. Possible combinations of growth factors and cytokines together with EPC transplantation may provide for a greater extent of vessel repair and new vessel formation.