Effects of Adipose Tissue-Derived Stem Cells Transplanted to a Bone Defect after Irradiation

Abstract

We examined whether the effect of adipose tissue-derived stem cell (ADSC) transplantation improved bone wounds healing irradiation. ADSCs were harvested from F344 rats and the cells cultured until the second passage for transplantation. Before ADSC transplantation, a single dose of 15 Gy irradiation was administered to the head of every rat using ¹³⁷Cs gamma-ray irradiation system, except for the rats of the control group. Two weeks after the irradiation, ADSCs were seeded on a carrier (collagen sponge) and transplanted into the bone defects formed on the rat parietal bones (the irradiation transplant group). This group was compared with two other groups: the carrier only group (without ADSCs) implanted after irradiation (the irradiation group) and; the group in which the carrier was implanted without irradiation (the control group). The results were obtained by histological, immunohistochemistry and ultrastructural observation. We examined the effects of ADSC transplantation on the delay of bone wound healing after irradiation. The new bone formation area of the irradiation group was significantly suppressed (p <0.05) as compared with the other groups. The vascular density at the site of new bone formation in the irradiation group decreased as compared with the other groups. In the irradiation transplant group, the BrdU positive cells were arranged like osteoblasts at the newly formed bone area and were also seen in the vascular wall and the interstitial tissue at the bone defect site. In the irradiation transplant group, VEGF positive cells appeared in blood vessels and the interstitial tissue in the bone defect area, whereas in the other groups, they were hardly found. ADSCs improved bone wound healing after irradiation by direct differentiation of bone forming cells and vascular endothelial cells. In addition, ADSCs have a paracrine effect which induces cell differentiation into VEGF positive cells which acts on angiogenesis.