title: Bioimaging assessment and effect of skin wound healing using bone-marrow-derived mesenchymal stromal cells with the artificial dermis in diabetic rats.
abstract: We investigate the relationship between the fate and healing effect of transplanted mesenchymal stromal cells (MSCs) in a rat diabetic skin wound model. Rats are treated with streptozotocin to induce diabetic conditions. A full-thickness skin defect is surgically made on the head of diabetic rats, and covered with an artificial dermis impregnated with either bone marrow cells (BMCs) or bone-marrow-derived MSCs from firefly luciferase (luc) transgenic (Tg) rats. Wound healing is evaluated using planimetry and immunohistochemistry, and the fate of transplanted MSCs is determined using in-vivo luminescent imaging. The diabetic wound treated with MSCs-impregnated artificial dermis is significantly smaller than that treated with artificial dermis alone at 1 week postoperation. Photons of luc+ MSCs are detected at the transplanted site during healing (3 weeks), whereas those of luc+ MSCs are depleted only after 1 week postimplantation. Immunohistochemistry at the healing site treated with MSCs demonstrates that CD31+ vessels increase with expression of vascular endothelial growth factor, suggesting that MSCs accelerate angiogenesis. These findings suggest that transplanted MSCs could be retained at wound sites during the healing process in a diabetic rat model, and subsequently promote wound healing through angiogenesis.
authors.affiliation: Jichi Medical University, Division of Organ Replacement Research, Center for Molecular Medicine and Department of Orthopedics, Tochigi 329-0498, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Murakami
authors.forename: Takashi
authors.initials: T
authors.lastname: Ajiki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Hara
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D048909:Diabetes Complications / Q000473:pathology* / Q000601:surgery*; D004195:Disease Models, Animal; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000473:pathology; D008856:Microscopy, Fluorescence / Q000379:methods; D051381:Rats; D011917:Rats, Inbred Lew; D012883:Skin Ulcer / Q000473:pathology* / Q000601:surgery*; D017768:Skin, Artificial; D016896:Treatment Outcome; D014945:Wound Healing