title: Human cord blood-derived endothelial progenitor cells and their conditioned media exhibit therapeutic equivalence for diabetic wound healing.
abstract: Transplantation of human cord blood-derived endothelial progenitor cells (EPCs) is reported to contribute to neovascularization in various ischemic diseases. However, the possible beneficial role and underlying mechanisms in diabetes-impaired wound healing have been less well characterized. In this study, EPC transplantation stimulated keratinocyte and fibroblast proliferation substantially as early as 3 days after injury, leading to significantly accelerated wound closure in streptozotocin-induced diabetic nude mice, compared to PBS control. RT-PCR analysis showed that EPCs secreted various wound healing-related growth factors. Among them, keratinocyte growth factor and platelet-derived growth factor were highly expressed in the EPCs and were present at substantial levels in the EPC-injected dermal tissue. Using EPC-conditioned medium (CM), we found that paracrine factors from EPCs directly exerted mitogenic and chemotactic effects on keratinocytes and fibroblasts. Moreover, injection of EPC-CM alone into the same diabetic wound mice promoted wound healing and increased neovascularization to a similar extent as achieved with EPC transplantation. These results indicate that the beneficial effect of EPC transplantation on diabetic wounds was mainly achieved by their direct paracrine action on keratinocytes, fibroblasts, and endothelial cells, rather than through their physical engraftment into host tissues (vasculogenesis). In addition, EPC-CM was shown to be therapeutically equivalent to EPCs, at least for the treatment of diabetic dermal wounds, suggesting that conditioned medium may serve as a novel therapeutic option that is free from allograft-associated immune rejection concern.
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Kangnam-gu, Seoul, Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Sun-Hwa
authors.initials: SH
authors.lastname: Song
authors.forename: Koung Li
authors.initials: KL
authors.lastname: Kim
authors.forename: Jeong-Jae
authors.initials: JJ
authors.lastname: Ko
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Im
authors.forename: Se Won
authors.initials: SW
authors.lastname: Yie
authors.forename: Young Keun
authors.initials: YK
authors.lastname: Ahn
authors.forename: Duk-Kyung
authors.initials: DK
authors.lastname: Kim
authors.forename: Wonhee
authors.initials: W
authors.lastname: Suh
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000737:chemistry*; D048909:Diabetes Complications / Q000628:therapy*; D003921:Diabetes Mellitus, Experimental; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014945:Wound Healing
chemical_list: D017077:Culture Media, Conditioned