Research status and progress on limb preservation technology / 器官移植

Limb replantation and transplantation is the optimal treatment for traumatic limb amputation. Safe and effective limb preservation is the key factor to determine the success of limb replantation and transplantation. Currently, static cold storage is the gold standard of limb preservation. However, the preservation time is short, which may no longer meet clinical requirements. With rapid development of organ preservation in recent years, novel preservation technologies, such as ultra-low temperature preservation, supercooling preservation and mechanical perfusion preservation, have successively emerged. However, at present, these techniques are primarily applied to the preservation of solid organs rather than composite tissue allografts with blood vessels including limbs. In this article, research status and progress on the application of static cold storage and mechanical perfusion preservation in limb preservation were reviewed, aiming to provide reference for clinical application of limb preservation technology and promote the development of limb replantation and transplantation.

Limb Transplantation: Indications and Recent Results

Hand is very important for daily living so most activities is impossible in bilateral amputation of the hand. Hand allotransplantation which was performed firstly in 1998 was epochal method for reconstruction of amputated hand to nearly normal hand. According to long term follow-up beyond 12 years, functional recovery of transplanted hand was inspiring and it was equal or even better than the result of replantation. The satisfactory results of transplantation spread it to worldwide and expand the consensus about the allotransplantation. But immunosuppressive therapy which followed consequently by transplantation induced many complications including infections, metabolic disease and cancer. Transplantation enhanced the quality of life but side effects of immunosuppressant threatened the life itself. So debate is ongoing about the ethical justification and indications of transplantation. This article reviews the recent results of hand transplantation and complications of immunosuppressive therapy.

Long-Term Acceptance of Fully Mhc-Mismatched Limb Allografts after a Short Course of Anti-alpha beta-T Cell Receptor Monoclonal Antibody and FK506

Whether a seven days course of anti-alpha beta cell receptor-antibody (alpha beta-TCRmAb) combined with FK506 therapy promotes survival of limb allografts in fully MHC-mismatched combination (Brown Norway --> Lewis) was examined. Eight animals received 250 microgram/kg/day of alpha beta-TCRmAb for 7 days and 2 mg/kg/day of FK506 postoperatively (Combination therapy group). Eight animals had FK506 only (Mono-therapy group) and five animals did not have treatment (Control group). Clinical signs of early rejection with edema or erythema in the skin occurred at an average of 8.6+/-1.5 days postoperatively in Control group and 59.0+/-8.3 days in Mono-therapy group, both of which proceeded to irreversible rejection with necrosis of the epidermis and finally mummification. In Combination therapy group, all animals showed evidence of early rejection at an average of 56.8+/-12.6 days postoperatively, however, in 4 of 8 limbs, early rejection resolved without any treatment and limbs survived >1 year. At 9 months postoperatively, donor skin grafts were accepted and third-party skin grafts were rejected by all four survivors, demonstrating donor-specific tolerance. Little or no detectable chimerism was observed in any of the 4 surviving animals at one-year postoperatively. Combination therapy of alphabeta-TCRmAb and FK506 resulted in long-term survival in fully MHC-mismatched limb transplants.

Experimental model for graft -versus-host disease in rat limb allotransplantation

Graft versus-host disease (GVHD) is a potentially fatal immune-regulated injury occurring unpredictably in solid organ and bone marrow transplant recipients. This model attempts the incidence of potentially lethal GVHD in limb transplants. Two inbred rat strains ACI and Lewis with a strong major and minor histocompatibility locus mismatch were studied. The perspectives of this model are study the incidence of GVHD in limb transplant, determine the best model for the study of the GVHD in limb transplant and prevention and treatment concerning the GVHD.

A Síndrome Enxerto versus Hospedeiro (SEVH) é uma condição imune potencialmente fatal que ocorre quando linfócitos transplantados do órgão doador reconhecem como estranho o tecido do receptor e tenta destruí-lo. Este modelo tem como objetivo verificar a incidência de SEVH em transplantes alógenos de membro. Duas espécies, ratos ACI e Lewis, lócus de maior e menor histocompatibilidade, foram combinadas. Determinar a incidência da SEVH nos transplantes alógenos de membro; estudar a regeneração nervosa e a toxicidade das drogas imunosupressoras; determinar a prevenção e o tratamento desta síndrome.