Treatment of Early Avascular Necrosis of Femoral Head by Small Intestinal Submucosal Matrix With Peripheral Blood Stem Cells

Abstract

Background Avascular necrosis of the femoral head (ANFH) is a highly mutilating disease. There are no effective ways to treat early femoral head ischemia. Peripheral blood stem cell (PBSC) transplantation may be superior to conventional bone marrow transplantation. Small intestinal submucosae matrix (SIS) is composed of highly conserved collagens, glycoproteins, proteoglycans, and glycoaminoglycans in their natural configuration and concentrations. When implanted in a number of microenvironments in vivo, SIS has been used to induce proliferation, remodeling, and regeneration of host tissues. This study was designed to verify the curative effects of PBSC and SIS transplantation–induced vascular regeneration to improve ischemic femoral head necrosis in rabbits. Methods 32 New Zealand white rabbits underwent ischemic femoral head necrosis modeling in both hindlimbs by liquid-nitrogen refrigeration. All rabbits were intraperitoneally injected with grannlocytectomy–stimulating factor (250 μg/kg/d), except for normal control subjects injected with equivalent saline solution. After separation of peripheral blood stem cells (PBSCs), 64 femoral heads in 32 rabbits were randomly divided into 4 groups: group A, cancellous bone and peripheral blood stem cells cultured with small intestinal submucosa; group B, cancellous bone and PBSCs; group C, cancellous bone autografts; and group D, no treatment. The specimens were harvested at 4 and 8 weeks after surgery. All specimens were examined to observe angiogenesis and osteogenesis repairing the avascular necrosis of the femoral head by using gross observation, x-ray, histology, and immunohistochemical staining. Results In 4 weeks after peripheral stem cell transplantation, the standing ability and activity of the transplanted hindlimbs were improved remarkably, but there were no obvious changes in the control limbs. X-rays showed a greater density of grafts than the host bone in groups A,B, and group C was unchanged at 4 weeks. Histology revealed many osteoprogenitor cells and osteoblasts and no inflammatory cell infiltration at 4 weeks with much new bone formed at 8 weeks in group A and at 4 weeks in group B. The cancellous bone autograft was absorbed completely at 8 weeks in group C. There was little osteoid tissue formed in group D at 8 weeks. The zone of new bone formation in group A was greater than that in group B ( P < .05), but there was no significant difference between groups A and C ( P > .05). Immunohistochemical staining with CD31 mouse antibody showed greater amounts and zones of new blood vessels in groups A and B at 4 and 8 weeks and little evidence in group D. There was no significant difference between groups A and B ( P > .05) and significant differences between groups A and B versus C and D ( P < .05). Conclusion Transplantation of PBSCs cultured with SIS effectively improved ischemic femoral head necrosis.