Reimplantation of growth plate chondrocytes into growth plate defects in sheep

Abstract

Defects in growth plates due to trauma, infection, or genetic causes can result in bone formation across the defect, bridging the epiphysis and metaphysis, resulting in growth arrest and limb deformation. We have investigated the capacity of implanted chondrocyte cultures to prevent this process. Sheep growth plate chondrocytes were isolated, and after culture at high density produced easily manipulated cartilaginous discs. The tissue was implanted into growth plate defects produced in lambs and the response was assessed histologically. Following implantation, cultures continued to proliferate and maintain a cartilage-like matrix. After 8 to 12 weeks, hypertrophic maturation chondrocyte columnation, and associated endochondral calcification were observed. Culture implantation was always associated with local immune inflammatory reaction, which continued throughout the course of investigation. Cellular survival was variable and resulted in the presence of viable implants as well as residual cartilage matrix devoid of chondrocytes; however, implanted chondrocyte discs always prevented bone bridge formation. These findings encourage the expectation that cultured chondrocytes may provide a useful replacement for the inert interpositional materials currently used in the treatment of growth arrest. The potential of this technique for growth plate replacement, however, requires a more predictable rate of implant survival. The likely reasons for implant loss are discussed.

Comparison of Preventive and Therapeutic Transplantations of Allogeneic Mesenchymal Stem Cells in Healing of the Distal Femoral Growth Plate Cartilage Defects in Miniature Pigs

“…Preventive interventions preventing the bone bridge formation focus on filling the occurred growth cartilage defect mainly with an allogeneic fat graft (Langenskiöld 1981), a graft from the fascia or tendon, or silicone substitutes (Macksoud and Bright 1989). Some studies point out the positive effect of autologous chondrocyte transplantation into the growth cartilage defect (Foster et al 1990;Lee et al 1998;Lennox et al 1983;Gál et al 2002a). In our previous studies we addressed the issue of transplantation of MSCs into the injured growth plates in pigs, mainly with the aim to find a suitable scaffold, and also to verify the possibilities and evaluate some aspects of autogenous and allogeneic transplantations of mesenchymal stem cells Gál et al 2007).…”

The effect of recombinant human osteogenic protein-1 on growth plate repair in a sheep model

“…Our laboratory has previously reported that this region is comparable with the growth plate from the unoperated limb [7,8,35]. Therefore, this region was used to represent a normal growth plate in this study.…”

Treatment of growth plate injury with autogenous chondrocytes

“…As regards fat and muscle tissues, insuf cient stiffness is commonly thought to disqualify them, since it weakens the grafted material. In transplant cases using cartilage, autogenous iliac apophysis (Olin et al 1984) and allogeneic chondrocytes (Foster et al 1990, Lee et al 1998) have been tried. A bone-bridge forms in sites where a dead space has developed between the uninjured growth plate and graft shortly after transplantation.…”

“…A bone-bridge forms in sites where a dead space has developed between the uninjured growth plate and graft shortly after transplantation. Furthermore, although excellent progress has been made with the allogeneic chondrocyte graft at 4 (Foster et al 1990) and 16 (Lee et al 1998) weeks after surgery, the nal outcomes may be poor, due to immunoresponse-related problems generated over a long period (Stevenson et al 1989). Recently, highly transmissible diseases, such as AIDS, have complicated the use of these grafts (Asselmeier et al 1993).…”

“…Although this procedure has been successful in clinical work, it has proved useful only when the extent of the injury is relatively limited and the growth plate has a framework strong enough to provide structural support even after the bone-bridge is resected (Langenskiöld et al 1986). Foster et al (1990) reported the use of cultured chondrocytes in collagen gel for repair of a physeal defect in a sheep model. This prevented the formation of a bone-bridge in a small physeal defect (less than 20% of the total physis).…”