Truong Wayne, Lakey Jonathan R T, Ryan Edmond A, Shapiro A M James
Clinical Islet Transplant Program, University of Alberta, Edmonton AB, Canada.
Clin Transpl. 2005:153-72.
While the field of islet transplantation has evolved over the past 30 years and exponential progress and increase in clinical activity has occurred during the past 5 years, it is clear that major challenges still remain, particularly in understanding why islet function seems to decay over time. High one-year rates of insulin independence, and high 5-year rates of partial islet function (with C-peptide secretion and protection from hypoglycemia) are now routine. Improved control of glycated HbA1c and reduced risk of recurrent hypoglycemia are benefits of islet transplantation irrespective of the status of insulin independence. If complete and sustained freedom from insulin is the primary objective, it is clear that whole pancreas transplantation still offers far superior metabolic reserve. However, the less interventional nature of islet infusion and avoidance of major surgery are advantages of islet transplantation over whole pancreas strategies. While the anti-rejection drugs available today may have had an acceptable safety profile in most islet transplant recipients, the drug-related and dose-limiting side effects have proved to be a challenge in some patients. Current islet-alone transplantation requires lifelong immunosuppression and is limited to patients with recurrent severe hypoglycemia and severe labile diabetes. More effective treatments are needed to control both acute rejection and recurrent autoimmunity. Remarkable opportunities lie ahead for improved islet survival, better engraftment and the possibility of expansion of islet mass both in culture and possibly within the patient after transplantation. Living-donor islet transplantation offers one option to expand the available donor supply, but remains controversial because of the potential for diabetes induction or other morbidities in a healthy donor. The development of less toxic immunosuppression and perhaps immunological tolerance will one day also have a huge impact on this field. Alternative tissue sources from either xenogenic sources or stem cells will ultimately solve the challenge of limited donor supply.
在过去30年里，胰岛移植领域不断发展，在过去5年中取得了指数级的进展，临床活动也有所增加，但显然仍存在重大挑战，尤其是在理解胰岛功能为何似乎会随时间衰退方面。目前，高比例的1年胰岛素非依赖率以及高比例的5年部分胰岛功能（伴有C肽分泌和预防低血糖）已很常见。无论胰岛素非依赖状态如何，改善糖化血红蛋白A1c的控制以及降低低血糖复发风险都是胰岛移植的益处。如果完全且持续摆脱胰岛素是主要目标，那么很明显，全胰腺移植仍具有远为优越的代谢储备。然而，胰岛输注的干预性较小以及避免大手术是胰岛移植相对于全胰腺策略的优势。虽然如今可用的抗排斥药物在大多数胰岛移植受者中可能具有可接受的安全性，但药物相关的剂量限制性副作用在一些患者中已被证明是一项挑战。目前单纯胰岛移植需要终身免疫抑制，且仅限于患有复发性严重低血糖和严重脆性糖尿病的患者。需要更有效的治疗方法来控制急性排斥和复发性自身免疫。在改善胰岛存活、提高植入率以及在培养中甚至移植后在患者体内扩大胰岛数量方面，未来有着显著的机遇。活体供体胰岛移植提供了一种扩大可用供体来源的选择，但由于可能导致健康供体患糖尿病或出现其他疾病，仍存在争议。毒性较小的免疫抑制以及或许免疫耐受的发展终有一天也会对该领域产生巨大影响。来自异种来源或干细胞的替代组织来源最终将解决供体来源有限的挑战。
