THE EFFECT OF IMPLANTS LOADED WITH AUTOLOGOUS MESENCHYMAL STEM-CELLS ON THE HEALING OF CANINE SEGMENTAL BONE DEFECTS

Bone marrow has been shown to contain a population of rare mesenchymal stem cells that are capable of forming bone, cartilage, and other con nective tissues. We examined the effect of cultured autologous mesench ymal stem cells on the healing of critical-sized (twenty-one-millimete r-long) segmental defects in the femora of adult female dogs. Autologo us mesenchymal stem cells were isolated from bone marrow, grown in cul ture, and loaded onto porous ceramic cylinders consisting of hydroxyap atite (65 per cent) and p-tricalcium phosphate ceramic (35 per cent). The animals were randomly assigned to one of three groups. In Group A (six dogs), a porous ceramic cylinder that had been loaded with autolo gous mesenchymal stem cells was implanted in the defect. In Group B (s ix dogs), a ceramic cylinder that had not been loaded with cells was p laced in the defect. In Group C (three dogs), the defect was left untr eated (no ceramic cylinder was implanted). Radiographs were made immed iately after the operation and at four-week intervals. At sixteen week s, the animals were killed, the involved femora were removed, and unde calcified histological sections from the defects and adjacent bone wer e prepared. Histological and histomorphometric studies were carried ou t to examine the healing of the defects and the formation of bone in a nd around the ceramic implants. Atrophic non-union occurred in all of the femora that had untreated defects, and only a small amount of trab ecular bone formed at the cut ends of the cortex of the host hone in t his group. In contrast, radiographic union was established rapidly at the interface between the host bone and the implants that had been loa ded with mesenchymal stem cells. Numerous fractures, which became more pronounced with time, developed in the implants that had not been loa ded with cells. Histological and morphometric analyses demonstrated th at both woven and lamellar bone had filled the pores of the implants t hat had been loaded with mesenchymal stem cells; the amount of bone wa s significantly greater (p < 0.05) than that found in the pores of the implants that had not been loaded with cells. In addition, a large co llar of bone (mean maximum thickness, 3.14 millimeters) formed around the implants that had been loaded with cells; this collar became integ rated and contiguous,vith callus that formed in the region of the peri osteum of the host bone. The collar of bone remodeled during the sixte en-week period of study, resulting in a size and shape that were compa rable with those of the segment of bone that had been resected, Callus did not develop around the cortex of the host bone or around the defe ct in any of the specimens in the other two groups. CLINICAL RELEVANCE : Autologous cultured bone-marrow-derived mesenchymal stem cells that had been loaded onto porous ceramic cylinders elicited the healing of critical-sized segmental bone defects in dogs. It may be possible to e xploit this technology to elicit the healing of bone defects in humans by using cells from bone marrow that has been aspirated from the ilia c crest of the patient, This approach may provide an alternative to au tologous bone-grafting and may be particularly useful when the number of endogenous mesenchymal stem cells is relatively small.