Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages.
Adult bone-marrow-derived mesenchymal stem cells (MSCs) are well-established as having the capacity to differentiate into cells with mesodermal, ectodermal, and endodermal characteristics and can leave their niche to home toward and engraft within foreign tissues. To investigate whether adult MSCs contribute to the repair of skin appendages after injury, BrdU-labeled MSCs were co-cultured with heat-shocked confluent sweat gland cells (SGCs) in vitro and later intravenously injected into full-thickness skin wounds in rats. When adult MSCs were co-cultured with heat-shocked SGCs, a subset of adult MSCs differentiated into SGCs, the percentage of differentiation being enhanced by epidermal growth factor and the injured microenviroment, but weakened by PD98059. The ERK (extracellular signal-regulated kinase) pathway, especially pERK, was involved in the phenotype conversion of human MSCs into human SGC. Labeled MSCs were noted in hair follicles, sebaceous glands, blood vessels, and dermis in full-thickness wounds, and the incorporated cells in hair follicles and sebaceous glands were also positive for pan-cytokeratin. After wound healing, some labeled MSCs returned to the bone marrow, whereas other were retained in the dermis. We conclude that adult MSCs have the capacity to dock at specific sites, to contribute to wound healing of skin appendages, and to home toward marrow, and that engraftment of bone-marrow-derived cells is a functional event.
Li
Haihong
H
Wound Healing and Cell Biology Laboratory, Burns Institute, The First Affiliated Hospital (304th Hospital), General Hospital of PLA, Trauma Center of Postgraduate Medical College, Beijing, People's Republic of China.
Fu
Xiaobing
X
Ouyang
Yunshu
Y
Cai
Cunliang
C
Wang
Jun
J
Sun
Tongzhu
T
D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000033:anatomy & histology*; D013545:Sweat Glands / Q000166:cytology* / Q000601:surgery / Q000637:transplantation; D013778:Tetrazolium Salts / Q000378:metabolism; D014183:Transplantation, Heterologous; D014945:Wound Healing / Q000502:physiology*
D015415:Biomarkers; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D013778:Tetrazolium Salts; D016222:Fibroblast Growth Factor 2; C011314:neotetrazolium; C035455:5-bromo-4-chloro-3-indoxyl phosphate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one