Enhanced wound healing by topical administration of mesenchymal stem cells transfected with stromal cell-derived factor-1.
The objective of this study was to investigate the ability of mesenchymal stem cells (MSC) genetically engineered with stromal cell-derived factor-1 (SDF-1) to heal skin wounds. When transfected with SDF-1 plasmid DNA, MSC which were isolated from the bone marrow of rats, secreted SDF-1 for 7 days. In vitro cell migration assay revealed that the SDF-1-engineered MSC (SDF-MSC) enhanced the migration of MSC and dermal fibroblasts to a significantly greater extent than MSC. The SDF-MSC secreted vascular endothelial growth factor, hepatocyte growth factor, and interleukin 6 at a significantly high level. A skin defect model of rats was prepared and MSC and SDF-MSC were applied to the wound to evaluate wound healing in terms of wound size and histological examinations. The wound size decreased significantly faster with SDF-MSC treatment than with MSC and PBS treatments. The length of the neoepithelium and the number of blood vessels newly formed were significantly larger. A cell-tracing experiment with fluorescently labeled cells demonstrated that the percent survival of SDF-MSC in the tissue treated was significantly high compared with that of MSC. It was concluded that SDF-1 genetic engineering is a promising way to promote the wound healing activity of MSC for a skin defect.
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Kyoto University, Japan; Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Japan. Electronic address: nyoko107@gmail.com.
Yoko
Y
Nakamura
Hidefumi
H
Ishikawa
Katsuya
K
Kawai
Yasuhiko
Y
Tabata
Shigehiko
S
Suzuki
D000287:Administration, Topical; D000818:Animals; D060846:Cell Engineering; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000293:injuries; D014162:Transfection; D014945:Wound Healing
D054377:Chemokine CXCL12
Mesenchymal stem cells; Non-viral vector; Skin wound healing; Stromal cell-derived factor-1