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胰腺和胰岛移植的当前挑战:一项范围综述

Current Challenges in Pancreas and Islet Transplantation: A Scoping Review.

作者信息

Altabas Velimir, Bulum Tomislav

机构信息

Department of Endocrinology, Diabetes and Metabolic Diseases Mladen Sekso, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia.

School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

出版信息

Biomedicines. 2024 Dec 15;12(12):2853. doi: 10.3390/biomedicines12122853.

Abstract

Type 1 diabetes mellitus is an autoimmune condition characterized by the destruction of pancreatic β-cells, necessitating insulin therapy to prevent life-threatening complications such as diabetic ketoacidosis. Despite advancements in glucose monitoring and pharmacological treatments, managing this disease remains challenging, often leading to long-term complications and psychological burdens, including diabetes distress. Advanced treatment options, such as whole-pancreas transplantation and islet transplantation, aim to restore insulin production and improve glucose control in selected patients with diabetes. The risk of transplant rejection necessitates immunosuppressive therapy, which increases susceptibility to infections and other adverse effects. Additionally, surgical complications, including infection and bleeding, are significant concerns, particularly for whole-pancreas transplantation. Recently, stem cell-derived therapies for type 1 diabetes have emerged as a promising alternative, offering potential solutions to overcome the limitations of formerly established transplantation methods. The purpose of this scoping review was to: (1) summarize the current evidence on achieved insulin independence following various transplantation methods of insulin-producing cells in patients with type 1 diabetes; (2) compare insulin independence rates among whole-pancreas transplantation, islet cell transplantation, and stem cell transplantation; and (3) identify limitations, challenges and potential future directions associated with these techniques. We systematically searched three databases (PubMed, Scopus, and Web of Science) from inception to November 2024, focusing on English-language, peer-reviewed clinical studies. The search terms used were 'transplantation' AND 'type 1 diabetes' AND 'insulin independence'. Studies were included if they reported on achieved insulin independence, involved more than 10 patients with type 1 diabetes, and had a mean follow-up period of at least one year. Reviewers screened citations and extracted data on transplant type, study population size, follow-up duration, and insulin independence rates. We identified 1380 papers, and after removing duplicates, 705 papers remained for title and abstract screening. A total of 139 English-language papers were retrieved for full-text review, of which 48 studies were included in this review. The findings of this scoping review indicate a growing body of literature on transplantation therapy for type 1 diabetes. However, significant limitations and challenges, like insufficient rates of achieved insulin independence, risks related to immunosuppression, malignant diseases, and ethical issues remain with each of the established techniques, highlighting the need for innovative approaches such as stem cell-derived islet transplantation to promote β-cell regeneration and protection.

摘要

1型糖尿病是一种自身免疫性疾病,其特征是胰腺β细胞被破坏,因此需要胰岛素治疗以预防危及生命的并发症,如糖尿病酮症酸中毒。尽管在血糖监测和药物治疗方面取得了进展,但管理这种疾病仍然具有挑战性,常常导致长期并发症和心理负担,包括糖尿病困扰。先进的治疗选择,如全胰腺移植和胰岛移植,旨在恢复胰岛素分泌并改善特定糖尿病患者的血糖控制。移植排斥反应的风险需要免疫抑制治疗,这增加了感染和其他不良反应的易感性。此外,手术并发症,包括感染和出血,是重大问题,尤其是对于全胰腺移植。最近,用于1型糖尿病的干细胞衍生疗法已成为一种有前景的替代方案,为克服先前已确立的移植方法的局限性提供了潜在解决方案。本范围综述的目的是:(1)总结目前关于1型糖尿病患者采用各种胰岛素产生细胞移植方法后实现胰岛素自主的证据;(2)比较全胰腺移植、胰岛细胞移植和干细胞移植之间的胰岛素自主率;(3)确定与这些技术相关的局限性、挑战和潜在的未来方向。我们系统地检索了三个数据库(PubMed、Scopus和Web of Science),从数据库创建到2024年11月,重点关注英文、同行评审的临床研究。使用的检索词是“移植” AND “1型糖尿病” AND “胰岛素自主”。如果研究报告了实现的胰岛素自主情况、涉及超过10名1型糖尿病患者且平均随访期至少为一年,则纳入研究。评审人员筛选了文献并提取了关于移植类型、研究人群规模、随访持续时间和胰岛素自主率的数据。我们识别出1380篇论文,去除重复项后,剩余705篇论文用于标题和摘要筛选。共检索到139篇英文论文进行全文评审,其中48项研究纳入了本综述。本范围综述的结果表明,关于1型糖尿病移植治疗的文献越来越多。然而,每种已确立的技术仍然存在重大局限性和挑战,如胰岛素自主率不足、与免疫抑制相关的风险、恶性疾病和伦理问题,这突出了对创新方法的需求,如干细胞衍生的胰岛移植,以促进β细胞再生和保护。

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