NERVE ALLOTRANSPLANTATION FOR TRAUMATIC NERVE INJURY

建立临床适用的诱导策略 供体特异性耐受允许神经同种异体移植， 这一提案的长期目标。 主要外周损伤 神经会导致严重的和永久性的功能缺陷。 同种异体神经移植材料的使用可避免并发症的发生 与获取神经自体移植物相关的，如疤痕，麻木， 或痛苦的神经瘤形成，并提供无限的神经来源， 移植材料重建大、多、复杂神经 受伤神经同种异体移植物保存的参数已经被 建立和冷移植物保存被认为是减少全身 环孢素A（CsA）要求。 针对以下疾病的单克隆抗体 粘附分子ICAM-1和LFA-1抑制同种异体神经移植 反应，但不能容忍动物。 相比之下， 用UV-B照射的脾细胞进行抗原预处理诱导 大鼠同种异体移植模型中的耐受性。 抗CD 4 mAb 功能性T细胞，从而导致宿主无反应性。 一 建立了一种可靠的绵羊神经移植模型 再生跨越一个长的神经间隙，更接近类似于 广泛神经损伤重建的临床挑战。七 同种异体神经冷保存30天， 同种异体移植物的抗原性，并允许神经再生。 因此，在本发明中， 与实体器官移植不同，同种异体移植物的保存使得 接受者用UV-B照射的供体抗原预处理（7天）， 临床上可行的同种异体移植 本提案的目的是 是：1）建立一个免疫抑制策略，使用预transp- 供体抗原联合抗CD 4 mAb的体内给药 在短神经同种异体移植物中诱导供体特异性耐受的疗法 研究CsA冷保存神经的优点 治疗和给予供体抗原以赋予免疫耐受， 沿着神经同种异体移植绵羊模型。评估技术将 包括混合淋巴细胞培养、细胞毒性T淋巴细胞测定， 有限稀释分析，结合组织学，形态学， 神经的逻辑、电生理和功能评估 再生这项建议的主要目标是改善 结果后，神经同种异体移植，从而允许建立 和促进临床神经同种异体移植- 是的。

The establishment of clinically applicable strategies for inducing donor-specific tolerance to allow nerve allograft transplantation is the long term objective of this proposal. Injury to major peripheral nerves can result in significant and permanent functional deficits. The use of allogeneic nerve graft material would avoid the morbidity associated with harvesting nerve autografts, such as scars, numbness, or painful neuroma formation, and offer a limitless source of nerve graft material to reconstruct large, multiple and complex nerve injuries. Parameters for nerve allograft preservation have been established and cold graft preservation is seen to decrease systemic Cyclosporin A (CsA) requirements. Monoclonal antibodIes (mAbs) against adhesion molecules, ICAM-1 and LFA-1, suppress the nerve allograft response but do not tolerize the animal. By contrast, donor-specific antigen pretreatment with UV-B irradiated spleen cells induces tolerance in the rat allograft model. Anti-CD4 mAbs inactivate functional T cells and thus, result in host unresponsiveness. A reliable sheep model has been developed to study nerve allograft regeneration across a long nerve gap that more closely resembles the clinical challenge of reconstruction of extensive nerve injuries. Seven days of cold preservation of the nerve allograft decreases the antigenicity of the allograft and allows nerve regeneration. Thus, unlike solid organ transplantation, preservation of the allograft makes recipient pretreatment with UV-B irradiated donor antigen(7 days) prior to allotransplantation clinically feasible. The aims of this proposal are: 1) to establish an immunosuppressive strategy that uses pretransp- lant administration of donor antigen in combination with anti-CD4 mAb therapy to induce donor-specific tolerance in a short nerve allograft rat model; and 2) to study the merits of cold nerve preservation CsA therapy and the administration of donor antigen to confer immunotolera- nce to along nerve allograft sheep model. Assessment techniques will include mixed lymphocyte culture, cytotoxic T lymphocyte assays and limiting dilutional analysis, in conjunction is histological, morpho- logical, electrophysiological and functional assessment of nerve regeneration. The broad objective of this proposal is to improve the results following nerve allografting and thus allow the establishment of a nerve bank and the facilitation of clinical nerve allotransplanta- tion.