Topical application of ex vivo expanded endothelial progenitor cells promotes vascularisation and wound healing in diabetic mice.
Impaired wound healing leading to skin ulceration is a serious complication of diabetes and may be caused by defective angiogenesis. Endothelial progenitor cells (EPCs) can augment neovascularisation in the ischaemic tissue. Experiments were performed to test the hypothesis that locally administered EPCs can promote wound healing in diabetes. Full-thickness skin wounds were created on the dorsum of diabetic mice. EPCs were obtained from bone marrow mononuclear cells (BMMNCs) and applied topically to the wound immediately after surgery. Vehicle and non-selective BMMNCs were used as controls. Wound size was measured on days 5, 10 and 14 after treatment, followed by resection, histological analysis and quantification of vascularity. Topical application of EPCs significantly promoted wound healing, as assessed by closure rate and wound vascularity. Immunostaining revealed that transplanted EPCs induced increased expression of vascular endothelial growth factor and basic fibroblast growth factor. Few EPCs were observed in the neovasculature based on in vivo staining of the functional vasculature. Ex vivo expanded EPCs promote wound healing in diabetic mice via mechanisms involving increased local cytokine expression and enhanced neovascularisation of the wound. This strategy exploiting the therapeutic capacity of autologously derived EPCs may be a novel approach to skin repair in diabetes.
Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan Division of Cardiovascular Research and Medicine, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA Department of Pharmacology, Osaka Medical College, Osaka, Japan Feinberg Cardiovascular Research Institute and Regenerative Medicine Program, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Jun
J
Asai
Hideya
H
Takenaka
Masaaki
M
Ii
Michio
M
Asahi
Saburo
S
Kishimoto
Norito
N
Katoh
Douglas W
DW
Losordo
D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental; D017719:Diabetic Foot / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D014945:Wound Healing / Q000502:physiology*