Systemic transplantation of progenitor cells accelerates wound epithelialization and neovascularization in the hairless mouse ear wound model.
BACKGROUND
Impaired wound healing due to local injury, infection, or systemic diseases, such as diabetes, is a major clinical problem. Recent studies have shown that endothelial progenitor cells (EPC) isolated from peripheral blood, bone marrow, as well as the spleen accumulate in granulation tissue at the site of neovascularization, causing secretion of growth factors and cytokines and thus accelerating wound healing.


METHODS
In the present study, we transplanted systemic EPC and then measured epithelialization and neovascularization in the hairless mouse ear wound model.


RESULTS
Systemic EPC transplantation significantly accelerated epithelialization and neovascularization compared with control wounds receiving phosphate-buffered saline without calcium and magnesium (PBS). The EPC group had significantly higher vascular density than did the PBS-treated group as determined by immunohistochemistry for CD31 and CD90. Fluorescence microscopy revealed accumulation "homing" of the transplanted EPC at the sites of neovascularization in the granulation tissue throughout healing. Furthermore, transplantation of EPC also increased the expression of the angiogenic cytokine stromal cell-derived factor 1α (SDF1α).


CONCLUSIONS
This appears to be the first demonstration of EPC recruitment to the site of wound neovascularization throughout the healing process. These findings demonstrate that transplanting systemic EPC into "normal" healing wounds promotes epithelialization and neovascularization and thus could be an useful method for accelerating wound healing.
Sander
Anna L
AL
Department of Trauma, Hand and Reconstructive Surgery, Hospital of the Johann Wolfgang Goethe-University, Frankfurt am Main, Germany. AnnaLena.Sander@kgu.de
Jakob
Heike
H
Henrich
Dirk
D
Powerski
Maciej
M
Witt
Helen
H
Dimmeler
Stefanie
S
Barker
John
J
Marzi
Ingo
I
Frank
Johannes
J
D000818:Animals; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D004431:Ear, External / Q000293:injuries; D004848:Epithelium / Q000502:physiology*; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D014945:Wound Healing / Q000502:physiology*
D054377:Chemokine CXCL12; D042461:Vascular Endothelial Growth Factor A