Exendin-4 enhances insulin-positive phenotype of human pluripotent stem cell-derived β cells during transplantation.

IF 12.1 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-07-16 DOI:10.1016/j.ymthe.2025.07.015

Kelly M Crumley,Elizabeth J Bealer,Anne C Lietzke,Scott A Soleimanpour,Lonnie D Shea

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引用次数: 0

Abstract

An emerging technique for the treatment of type 1 diabetes, which is characterized by hyperglycemia resulting from the loss of insulin-secreting β cells, involves transplantation of human pluripotent stem cell (hPSC)-derived β cells. This transplantation procedure can induce normoglycemia, yet the efficiency of cell survival and function post transplantation remain opportunities for improvement. Here, we investigated treatment with Exendin-4, a GLP-1 receptor agonist, throughout the post-transplantation period to improve the survival and function of transplanted cells. hPSC-derived β cell clusters were transplanted on microporous PLG scaffolds into the peritoneal fat, with Exendin-4 delivery resulting in a more rapid restoration of normoglycemia relative to control. We interrogated multiple avenues by which Exendin-4 enhanced transplantation, and observed a higher rate of cell survival, increased expression of maturation markers and greater metabolic outputs than untreated cells. Collectively, Exendin-4 delivered alongside hPSC-derived β cell transplantation decreased time to improved blood glucose levels and enhanced β cell number, differentiation, and maturation.

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Exendin-4增强人多能干细胞来源的β细胞在移植过程中的胰岛素阳性表型。

1型糖尿病的特点是胰岛素分泌β细胞缺失导致高血糖，一种新兴的治疗技术涉及人类多能干细胞（hPSC）来源的β细胞移植。这种移植方法可以诱导正常血糖，但移植后细胞存活和功能的效率仍有待提高。在这里，我们研究了在移植后使用Exendin-4（一种GLP-1受体激动剂）来改善移植细胞的存活和功能。将hpsc衍生的β细胞簇通过微孔PLG支架移植到腹膜脂肪中，与对照组相比，Exendin-4的递送使正常血糖恢复得更快。我们研究了Exendin-4促进移植的多种途径，并观察到与未经处理的细胞相比，Exendin-4提高了细胞存活率，增加了成熟标志物的表达，并增加了代谢输出。总的来说，Exendin-4与hpsc来源的β细胞移植一起递送，减少了改善血糖水平和增强β细胞数量、分化和成熟的时间。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.