Feng Xingrong, Zhang Hongmei, Yang Shanshan, Cui Daxin, Wu Yanting, Qi Xiaocun, Su Zhiguang
Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, China.
Mol Cell Biochem. 2025 Jan;480(1):173-190. doi: 10.1007/s11010-024-04999-x. Epub 2024 Apr 20.
Loss and functional failure of pancreatic β-cells results in disruption of glucose homeostasis and progression of diabetes. Although whole pancreas or pancreatic islet transplantation serves as a promising approach for β-cell replenishment and diabetes therapy, the severe scarcity of donor islets makes it unattainable for most diabetic patients. Stem cells, particularly induced pluripotent stem cells (iPSCs), are promising for the treatment of diabetes owing to their self-renewal capacity and ability to differentiate into functional β-cells. In this review, we first introduce the development of functional β-cells and their heterogeneity and then turn to highlight recent advances in the generation of β-cells from stem cells and their potential applications in disease modeling, drug discovery and clinical therapy. Finally, we have discussed the current challenges in developing stem cell-based therapeutic strategies for improving the treatment of diabetes. Although some significant technical hurdles remain, stem cells offer great hope for patients with diabetes and will certainly transform future clinical practice.
胰腺β细胞的丢失和功能衰竭会导致葡萄糖稳态的破坏和糖尿病的进展。尽管全胰腺或胰岛移植是补充β细胞和治疗糖尿病的一种有前景的方法,但供体胰岛的严重短缺使得大多数糖尿病患者无法实现这一目标。干细胞,特别是诱导多能干细胞(iPSCs),因其自我更新能力和分化为功能性β细胞的能力,在糖尿病治疗方面具有广阔前景。在这篇综述中,我们首先介绍功能性β细胞的发育及其异质性,然后着重强调从干细胞生成β细胞的最新进展及其在疾病建模、药物发现和临床治疗中的潜在应用。最后,我们讨论了开发基于干细胞的治疗策略以改善糖尿病治疗目前面临的挑战。尽管仍然存在一些重大技术障碍,但干细胞为糖尿病患者带来了巨大希望,必将改变未来的临床实践。