Cell Isolation and Transplantation Center, Department of Surgery, University of Geneva School of Medicine, Geneva, Switzerland; Division of Transplantation, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland; Faculty Diabetes Center, University of Geneva School of Medicine, Geneva, Switzerland; Department of Surgery, School of Medicine and Natural Sciences, Ilia State University, Tbilisi, Georgia.
Cell Isolation and Transplantation Center, Department of Surgery, University of Geneva School of Medicine, Geneva, Switzerland; Division of Transplantation, Department of Surgery, University of Geneva Hospitals, Geneva, Switzerland.
Presse Med. 2022 Dec;51(4):104139. doi: 10.1016/j.lpm.2022.104139. Epub 2022 Oct 4.
Type 1 diabetes is a disease resulting from autoimmune destruction of the insulin-producing beta cells in the pancreas. When type 1 diabetes develops into severe secondary complications, in particular end-stage nephropathy, or life-threatening severe hypoglycemia, the best therapeutic approach is pancreas transplantation, or more recently transplantation of the pancreatic islets of Langerhans. Islet transplantation is a cell therapy procedure, that is minimally invasive and has a low morbidity, but does not display the same rate of functional success as the more invasive pancreas transplantation because of suboptimal engraftment and survival. Another issue is that pancreas or islet transplantation (collectively known as beta cell replacement therapy) is limited by the shortage of organ donors and by the need for lifelong immunosuppression to prevent immune rejection and recurrence of autoimmunity. A bioartificial pancreas is a construct made of functional, insulin-producing tissue, embedded in an anti-inflammatory, immunomodulatory microenvironment and encapsulated in a perm-selective membrane allowing glucose sensing and insulin release, but isolating from attacks by cells of the immune system. A successful bioartificial pancreas would address the issues of engraftment, survival and rejection. Inclusion of unlimited sources of insulin-producing cells, such as xenogeneic porcine islets or stem cell-derived beta cells would further solve the problem of organ shortage. This article reviews the current status of clinical islet transplantation, the strategies aiming at developing a bioartificial pancreas, the clinical trials conducted in the field and the perspectives for further progress.
1 型糖尿病是一种由自身免疫引起的疾病，导致胰腺中产生胰岛素的β细胞被破坏。当 1 型糖尿病发展为严重的继发性并发症，特别是终末期肾病或危及生命的严重低血糖时，最佳治疗方法是胰腺移植，或最近的胰岛移植。胰岛移植是一种细胞治疗程序，微创，发病率低，但由于移植物植入和存活不佳，其功能成功率不如更具侵入性的胰腺移植高。另一个问题是，胰腺或胰岛移植（统称为β细胞替代治疗）受到器官供体短缺的限制，并且需要终身免疫抑制以防止免疫排斥和自身免疫的复发。生物人工胰腺是一种由功能性、产生胰岛素的组织构成的构建体，嵌入在抗炎、免疫调节的微环境中，并封装在允许葡萄糖感测和胰岛素释放但隔离免疫系统细胞攻击的可渗透选择性膜中。一个成功的生物人工胰腺将解决植入、存活和排斥的问题。纳入无限来源的胰岛素产生细胞，如异种猪胰岛或干细胞衍生的β细胞，将进一步解决器官短缺的问题。本文综述了临床胰岛移植的现状、开发生物人工胰腺的策略、该领域的临床试验以及进一步进展的展望。
