Prevention of osteonecrosis by intravenous administration of human peripheral blood-derived CD34-positive cells in a rat osteonecrosis model.
Aseptic idiopathic osteonecrosis of the femoral head is a painful disorder of the hip that can lead to collapse of the femoral head and the need for total hip replacement following joint destruction. Treatment of this disease still remains a clinical challenge. Adult human circulating CD34(+) cells have been demonstrated to contribute to vasculogenesis and osteogenesis in immunodeficient rat non-union models in vivo. We hypothesized and proved that the transplantation of CD34(+) cells could have a role for improvement of osteonecrosis by promoting vasculogenesis and osteogenesis. Vascular deprivation-induced femoral head necrosis was developed in immunodeficient rats and we then administered human G-CSF mobilized CD34(+) cells intravenously. At 4 weeks after administration, the structure of the femoral head and neck were evaluated histologically and morphometrically with haematoxylin and eosin (H&E) staining and micro-CT imaging. Microangiography was carried out for macroscopic evaluation of neovascularization, and the contribution of human cells to vasculogenesis and osteogenesis was evaluated by immunofluorescent staining with human-specific antibodies. Our treatment resulted in an obvious improvement of osteonecrosis after CD34(+) cell administration and demonstrated the differentiation potential of CD34(+) cells into endothelial cells and osteoblasts. In conclusion, this new therapeutic approach using circulating cell fraction could be a promising cell-based therapy for early-stage osteonecrosis of the hip.
Terayama
Hiroshi
H
Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Japan.
Ishikawa
Masakazu
M
Yasunaga
Yuji
Y
Yamasaki
Takuma
T
Hamaki
Takanari
T
Asahara
Takayuki
T
Ochi
Mitsuo
M
D000328:Adult; D000792:Angiography; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001773:Blood Cells / Q000637:transplantation*; D004195:Disease Models, Animal; D005260:Female; D005270:Femur Head / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D005271:Femur Head Necrosis / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery / Q000628:therapy*; D006801:Humans; D007275:Injections, Intravenous; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D051381:Rats; D011923:Rats, Nude; D055114:X-Ray Microtomography; D055815:Young Adult
D018952:Antigens, CD34