Prevention of osteonecrosis by intravenous administration of human peripheral blood-derived CD34-positive cells in a rat osteonecrosis model

Abstract

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.