Transplantation of Endothelial Progenitor Cells Accelerates Dermal Wound Healing with Increased Recruitment of Monocytes/Macrophages and Neovascularization

Abstract

Endothelial progenitor cells (EPCs) act as endothelial precursors that promote new blood vessel formation and increase angiogenesis by secreting growth factors and cytokines in ischemic tissues. These facts prompt the hypothesis that EPC transplantation should accelerate the wound-repair process by facilitating neovascularization and the production of various molecules related to wound healing. In a murine dermal excisional wound model, EPC transplantation accelerated wound re-epithelialization compared with the transplantation of mature endothelial cells (ECs) in control mice. When the wounds were analyzed immunohistochemically, the EPCtransplanted group exhibited significantly more monocytes/ macrophages in the wound at day 5 after injury than did the EC-transplanted group. This observation is consistent with enzyme-linked immunosorbent assay results showing that EPCs produced in abundance several chemoattractants of monocytes and macrophages that are known to play a pivotal role in the early phase of wound healing. At day 14 after injury, the EPC-transplanted group showed a statistically significant increase in vascular density in the granulation tissue relative to that of the EC-transplanted group. Fluorescence microscopy revealed that EPCs preferentially moved into the wound and were directly incorporated into newly formed capillaries in the granulation tissue. These results suggest that EPC transplantation will be useful in dermal wound repair and skin regeneration, because EPCs both promote the recruitment of monocytes/macrophages into the wound and increase neovascularization. Stem Cells 2005;23:1571-1578

Material-based deployment enhances efficacy of endothelial progenitor cells

“…EPCs and OECs each provided benefit when delivered individually, but together they provided a greater benefit in this particular model of PAD. These results suggest this approach will be useful to treat cardiac infarction (44), and other situations in which vascularization is lacking (e.g., wound healing) (45). More broadly, this may provide a core technology for the entire field of regenerative medicine, because of the need to create new vascular beds in most situations of regeneration and tissue engineering (16).…”

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

“…Angiogenesis is initially induced by tissue destruction and hypoxia and is subsequently stimulated by various molecules such as basic fibroblast growth factor, VEGF, and transforming growth factor-β, secreted by macrophages, keratinocytes, and endothelial cells. A role of EPCs in granulation tissue formation is directly suggested by experiments demonstrating that cell therapy with EPCs enhances wound healing in mice (Suh et al 2005). The release of various growth factors such as VEGF and platelet-derived growth factor by EPCs appears to enhance wound healing (Suh et al 2005).…”

“…A role of EPCs in granulation tissue formation is directly suggested by experiments demonstrating that cell therapy with EPCs enhances wound healing in mice (Suh et al 2005). The release of various growth factors such as VEGF and platelet-derived growth factor by EPCs appears to enhance wound healing (Suh et al 2005). Reepithelialisation is the term used to describe the appearance of a new epithelial layer on top of a healing skin wound.…”

Cells as vehicles for therapeutic genes to treat liver diseases

“…44, 45 Suh and co-workers reported that human EPC obtained by Cells as vehicles for therapeutic genes J Prieto et al culturing in specific medium peripheral blood mononuclear cells and given to nude mice induced an acceleration of wound healing by local production of growth factors, stimulation of tissue repair and neovascularization. 46 In 2006, Taniguchi et al 47 showed that EPC obtained from human peripheral blood mononuclear cells or from murine BM after culture in specific medium for 10 days and given intrasplenically were able to ameliorate acute carbon tetrachloride liver damage in nude mice (human EPC) or in BALB/c mice (murine EPC) and to improve survival. They demonstrated that EPC generated high levels of hepatocyte growth factor, VEGF and heparin-binding EGF-like growth factor and stimulated the endogenous production of VEGF.…”