IGF-1 and chondroitinase ABC augment nerve regeneration after vascularized composite limb allotransplantation

Impaired nerve regeneration and inadequate recovery of motor and sensory function following peripheral nerve repair remain the most significant hurdles to optimal functional and quality of life outcomes in vascularized tissue allotransplantation (VCA). Neurotherapeutics such as Insulin-like Growth Factor-1 (IGF-1) and chondroitinase ABC (CH) have shown promise in augmenting or accelerating nerve regeneration in experimental models and may have potential in VCA. The aim of this study was to evaluate the efficacy of low dose IGF-1, CH or their combination (IGF-1+CH) on nerve regeneration following VCA. We used an allogeneic rat hind limb VCA model maintained on low-dose FK506 (tacrolimus) therapy to prevent rejection. Experimental animals received neurotherapeutics administered intraoperatively as multiple intraneural injections. The IGF-1 and IGF-1+CH groups received daily IGF-1 (intramuscular and intraneural injections). Histomorphometry and immunohistochemistry were used to evaluate outcomes at five weeks. Overall, compared to controls, all experimental groups showed improvements in nerve and muscle (gastrocnemius) histomorphometry. The IGF-1 group demonstrated superior distal regeneration as confirmed by Schwann cell (SC) immunohistochemistry as well as some degree of extrafascicular regeneration. IGF-1 and CH effectively promote nerve regeneration after VCA as confirmed by histomorphometric and immunohistochemical outcomes

Second report (1998-2006) of the International Registry of Hand and Composite Tissue Transplantation

Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This report provides a review of all hand transplants performed to date. From September 1998 to February 2006 eighteen male patients underwent 24 hand/forearm/digit transplantations (eleven unilateral and four bilateral hand transplantations, two bilateral forearm transplantations, one thumb transplantation). The level of amputation was mostly at the distal forearm or wrist. Patient average age was 32. Time since hand loss ranged from 2 months to 22 years. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Follow-up period ranged from 34 to 85 months. Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Two cases of graft failure at a later date occurred and were caused by severe inflammation and progressive rejection in a non-compliant patient. In addition, 6 hands were lost due to a rejection process as the Chinese recipients did not take their immunosuppressive treatment. These failures were communicated in January 2006. Acute rejection episodes occurred in 12 patients within the first year. Rejection was completely reversible in all compliant patients. Side-effects included opportunistic infections and metabolic complications. No life-threatening complications or malignancies were reported. As it would have been very difficult to analyse transplantation functional results in a standardized way, the Registry has performed a functional score system. All patients had achieved protective sensation and in 17 of them also discriminative sensation. Extrinsic and intrinsic muscle recovery enabled patients to perform most daily activities and 90% of the recipients returned to work, and improved manual skills allowed them not only to resume their previous jobs but also, in some cases, to find more suitable employment. Fifteen recipients reported an improvement of their quality of life and we evaluated as a very important point as patient satisfaction and well-being are mandatory goals of hand transplantation