Transplants of Rat Chondrocytes Evoke Strong Humoral Response against Chondrocyte-Associated Antigen in Rabbits

Abstract

Rat chondrocytes transplanted intramuscularly in rabbits produced cartilage. In 1-day-old transplants chondrocytes remained viable. After 1 week peripheral chondrocytes of the transplant were dead and the cartilage was surrounded and resorbed by macrophages. In 2-week-old transplants cartilage deteriorated and was invaded by fibroblast-like cells and macrophages. Sera of rabbits that received two or three consecutive transplants of rat chondrocytes with 2-week intervals contained high titer of antichondrocyte cytotoxic antibodies. A part of the cytotoxic activity could be removed by absorption with rat splenocytes. Western blot analysis of lysates from fresh or 24-h cultured chondrocytes with absorbed sera detected antigen with M r of ϳ74 and ϳ23 kDa. Only the latter remained after reduction in 2-mercaptoethanol. In lysates of fibroblasts and endotheliocytes the 23-kDa antigen was not found but the serum reacted with M r 39-kDa antigen. In lysates of thymocytes a weak band corresponding to M r of 35 kDa was present. Serum from rabbits receiving transplants of living chondrocytes followed by chondrocytes suspended in complete Freund's adjuvant contained antibodies directed against components of crude collagenase used for cell isolation. Such antibodies could not be detected in sera of rabbits receiving transplants of living chondrocytes only. Molecular weight of detected antigen differs from that of collagen type II, core of aggrecan, link proteins, and several other macromolecules of cartilage matrix. It could represent either a component of chondrocyte membrane or a membrane-bound substance resistant to enzymes used for isolation. Availability of antibodies against presumably chondrocyte-specific antigen produced during transplant rejection may help to characterize it more precisely and to ascertain whether its presence may influence results of autogenous chondrocyte transplants in humans.

Failure of xenoimplantation using porcine synovium‐derived stem cell‐based cartilage tissue constructs for the repair of rabbit osteochondral defects

“…16 Another study showed that rat cartilage transplants were rejected 2 weeks after implantation in intramuscular rabbit tissue. 17 Intriguingly, other xenoimplantation studies draw a different conclusion. 18,19 Rabbit articular cartilage defects xenotransplanted with porcine chondrocytes and covered with a periosteal graft for 6 months resulted in significantly more repair tissue and a better histologic score compared with only periosteal grafted controls.…”

Experimental study of tissue-engineered cartilage allograft with RNAi chondrocytes in vivo

“…Clinical and experimental observations have established that transplants of allogenic cartilage usually resist rejection,7 while on the other hand, transplants of isolated allogenic chondrocytes evoke a strong reaction leading to cartilage resorption by infiltrating cells 2. This particular feature can be explained by the fact that the chondrocytes constitutively express MHC I and possibly possess specific differentiation antigen;8,9 however, the chondrocyte’s integrity is sequestered by the affluent matrix, thus preventing their contact with the host immunocompetent cells as the matrix does not allow permeability of molecules greater than 60 kDa 7. The rejection and resorption of cartilage has also been observed in the transplantation of tissue engineering cartilage constructed by allogenic chondrocytes 2.…”

Clinical and experimental approaches to knee cartilage lesion repair and mesenchymal stem cell chondrocyte differentiation

“…Although intramuscular xenografts of rat chondrocytes into a rabbit host readily generated an important humoral immune response due to the high vascularity of the tissue (Osiecka-Iwan et al, 2003), diff erent results have been reported when the xenografts were implanted into a cartilage defect inside the joint, which is considered an immuno-privileged environment as it is avascular (Bolano and Kopta, 1991). One study addressing this used pig chondrocytes implanted into human cartilage defects in vitro and showed an important degree of wound filling and the synthesis of important levels of collagen fi bers (types I and II) and proteoglycans .…”