Bertuzzi Federico, Marzorati Simona, Secchi Antonio
Unit of Cell Therapy for Type 1 Diabetes, San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy.
Curr Mol Med. 2006 Jun;6(4):369-74. doi: 10.2174/156652406777435453.
Islet cell transplantation is an attractive alternative therapy to conventional insulin treatment or vascularized whole pancreas transplantation for type 1 diabetic patients. It represents a successful example of somatic cell therapy in humans based on complex procedures for islet isolation from whole pancreas. The islets, that are only 1% of the total pancreas tissue, are isolated by two steps method starting with collagenase digestion that operates a rapid dissociation of the stromal component of the gland, while preserving islet anatomical integrity. After digestion, islets are then separated from exocrine tissue by centrifugation in density gradients. Transplantation consists of a simple injection of few milliliter-purified tissue in the portal vein through a percutaneous trans-hepatic approach performed in local anesthesia. Several studies have now demonstrated that islet transplant can replace pancreatic endocrine function without major side effects and with liver viability preservation in selected patients affected by long-term type 1 diabetes. It can restore endogenous insulin secretion, achieve insulin independence in more than 80% of patients, and recover the metabolism of glucose, protein and lipids. Improved control of glycated HbA1c, reduced risk of recurrent hypoglycemia and of diabetic complications are also seen as important benefits of islet cell transplantation, irrespective of the status of insulin independence. Many protocols are now on going for reduction of immunosuppression therapy in recipients, induction of tolerance, and prolongation of graft function.
胰岛移植对于1型糖尿病患者而言,是一种有吸引力的替代疗法,可替代传统的胰岛素治疗或血管化全胰腺移植。它是基于从全胰腺分离胰岛的复杂程序,在人类体细胞治疗方面取得成功的一个范例。胰岛仅占胰腺组织总量的1%,通过两步法进行分离,首先是胶原酶消化,这能快速分离腺体的间质成分,同时保持胰岛的解剖完整性。消化后,通过密度梯度离心将胰岛与外分泌组织分离。移植是在局部麻醉下,通过经皮经肝途径向门静脉简单注射几毫升纯化组织。现在有多项研究表明,胰岛移植可以替代胰腺内分泌功能,对患有长期1型糖尿病的特定患者而言,没有重大副作用且能保留肝脏活力。它可以恢复内源性胰岛素分泌,使超过80%的患者实现胰岛素自主,并恢复葡萄糖、蛋白质和脂质的代谢。无论胰岛素自主状态如何,糖化血红蛋白A1c控制改善、低血糖复发风险降低以及糖尿病并发症风险降低,也都被视为胰岛细胞移植的重要益处。现在有许多方案正在进行,旨在减少受者的免疫抑制治疗、诱导免疫耐受以及延长移植物功能。