Mesenchymal stem cell therapy for cutaneous radiation syndrome.
Systemic and local radiation injuries caused by nuclear power reactor accidents, therapeutic irradiation, or nuclear terrorism should be prevented or properly treated in order to improve wound management and save lives. Currently, regenerative surgical modalities should be attempted with temporal artificial dermis impregnated and sprayed with a local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Human mesenchymal stem cells and adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and were tested for differentiation and local stimulation effects in the radiation-exposed wounds. The perforator flap and artificial dermal template with growth factor were successful for reconstruction in patients who were suffering from complex underlying disease. Patients were uneventfully treated with minimal morbidities. In the experiments, the hMSCs are strongly proliferative even after 20 Gy irradiation in vitro. In vivo, 4 Gy rat whole body irradiation demonstrated that sustained marrow stromal (mesenchymal stem) cells survived in the bone marrow. Immediate artificial dermis application impregnated with cells and the cytokine over the 20 Gy irradiated skin and soft tissues demonstrated the significantly improved fat angiogenesis, architected dermal reconstitution, and less inflammatory epidermal recovery. Detailed understanding of underlying diseases and rational reconstructive procedures brings about good outcomes for difficult irradiated wound healing. Adipose-derived stem cells are also implicated in the limited local injuries for short cell harvesting and processing time in the same subject.
Akita
Sadanori
S
Department of Plastic and Reconstructive Surgery, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. akitas@hf.rim.or.jp
Akino
Kozo
K
Hirano
Akiyoshi
A
Ohtsuru
Akira
A
Yamashita
Shunichi
S
D000273:Adipose Tissue / Q000166:cytology; D000368:Aged; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008875:Middle Aged; D011832:Radiation Injuries / Q000628:therapy*; D051381:Rats; D012867:Skin / Q000528:radiation effects*; D012871:Skin Diseases / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology
D016207:Cytokines; D016222:Fibroblast Growth Factor 2