Survival of microvascular physeal allograft transplants following withdrawal of short-term postoperative immunosuppression. 2004

Peter W Bray, and Peter C Neligan, and C Vaughan A Bowen, and Martin I Boyer
Division of Surgical Research, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.

BACKGROUND Physeal necrosis following vascularized allograft transplantation occurs because of vascular rejection. The effect of immunosuppression withdrawal on physeal viability after bone-healing to the recipient site was investigated with use of a validated model for heterotopic microvascular transplantation of rabbit tibial physeal allografts. Our hypothesis was that an allograft survives after withdrawal of immunosuppression only if bone-healing, and therefore epiphyseal and metaphyseal vascular continuity, occurs between the transplanted physis and the recipient bone. METHODS Physeal grafts with adjacent exposed epiphyseal and metaphyseal bone were transplanted to allogeneic recipients. Graft circulation was restored microsurgically. The immunosuppression regimen consisted of cyclosporine, administered for six weeks, followed by withdrawal of immunosuppression for four weeks. The animals were killed at ten weeks postoperatively. Group I consisted of twelve allografts that were transferred with bone contact between the transplanted graft and the iliac crest recipient site, whereas group II consisted of twelve allografts transplanted without bone contact. Control groups had identical surgical procedures without immunosuppression. Longitudinal growth was assessed by fine-detail radiography, and osseous union was evaluated histologically. Transplanted physes were evaluated histologically, and cellular viability was quantified by bromodeoxyuridine uptake. Two-way analysis of variance was used to compare physeal viability between groups. RESULTS Following immunosuppression withdrawal, the physeal grafts with bone contact had significantly greater viability indices (16.0 +/- 2.9 compared with 0.0 +/- 0.0, p < 0.005) and decreased longitudinal growth (5.1 +/- 1.9 mm compared with 10.3 +/- 3.5 mm, p < 0.05), and they demonstrated histological features that were consistent with continued viability associated with mild rejection compared with grafts transplanted without bone contact. Abnormalities of physeal architecture, however, were seen routinely. All control physes transferred without immunosuppression were nonviable and did not grow. CONCLUSIONS The viability of physeal allograft transplants is preserved following the withdrawal of immunosuppression, provided that the graft design and recipient site preparation allow for epiphyseal and metaphyseal neovascularization mediated by bone-healing between graft and recipient.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008833 Microcirculation The circulation of the BLOOD through the MICROVASCULAR NETWORK. Microvascular Blood Flow,Microvascular Circulation,Blood Flow, Microvascular,Circulation, Microvascular,Flow, Microvascular Blood,Microvascular Blood Flows,Microvascular Circulations
D011182 Postoperative Care The period of care beginning when the patient is removed from surgery and aimed at meeting the patient's psychological and physical needs directly after surgery. (From Dictionary of Health Services Management, 2d ed) Care, Postoperative,Postoperative Procedures,Procedures, Postoperative,Postoperative Procedure,Procedure, Postoperative
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D005260 Female Females
D006085 Graft Survival The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. Graft Survivals,Survival, Graft,Survivals, Graft
D006132 Growth Plate The area between the EPIPHYSIS and the DIAPHYSIS within which bone growth occurs. Cartilage, Epiphyseal,Epiphyseal Cartilage,Epiphyseal Plate,Cartilages, Epiphyseal,Epiphyseal Cartilages,Epiphyseal Plates,Growth Plates,Plate, Epiphyseal,Plate, Growth,Plates, Epiphyseal,Plates, Growth
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D016572 Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed). Cyclosporin A,Ciclosporin,CsA-Neoral,CyA-NOF,Cyclosporin,Cyclosporine A,Neoral,OL 27-400,Sandimmun,Sandimmun Neoral,Sandimmune,CsA Neoral,CsANeoral,CyA NOF,OL 27 400,OL 27400

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