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First published online August 4, 2005
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2004-0340v1
23/10/1571    most recent
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Submitted on December 1, 2004
Accepted on May 24, 2005

Original Article

Transplantation of endothelial progenitor cells accelerates dermal wound healing with increased recruitment of monocytes/macrophages and neovascularization

Wonhee Suh 1, Koung Li Kim 1, Jeong-Min Kim 1, In-Soon Shin 1, Young-Sam Lee 1, Jae-Young Lee 1, Hyung-Suk Jang 1, Jung-Sun Lee 1, Jonghoe Byun 1, Jin-Ho Choi 1, Eun-Seok Jeon 1, Duk-Kyung Kim 1*

1 Department of Medicine, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, KOREA

* To whom correspondence should be addressed. E-mail: dkkim{at}smc.samsung.co.kr.


   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 reepithelialization compared with the transplantation of mature endothelial cells (ECs) in control mice. When the wounds were analyzed immunohistochemically, the EPC-transplanted 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 ELISA 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.

Key Words. endothelial progenitor cell, macrophage, monocyte, neovascularization, wound healing




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