新兴糖尿病疗法:再生胰腺 β 细胞。
Emerging Diabetes Therapies: Regenerating Pancreatic β Cells.
发表日期:2024 Sep 27
作者:
Haojie Zhang, Yaxin Wei, Yubo Wang, Jialin Liang, Yifan Hou, Xiaobo Nie, Junqing Hou
来源:
Tissue Engineering Part B-Reviews
摘要:
糖尿病 (DM) 的发病率逐年稳步上升,截至 2021 年,糖尿病患者数量已达 5.37 亿。恢复减少的 β 细胞量或受损的胰岛功能对于治疗 DM,尤其是 1 型 DM 至关重要。然而,主要产生胰岛素的胰岛β细胞的再生能力受到严重限制,并且仅在年幼的啮齿动物或儿童中观察到自然再生。因此,迫切需要开发先进的治疗方法,可以再生内源性β细胞或用干细胞(SC)衍生的或工程化的β样细胞替代它们。目前治疗胰岛素依赖型糖尿病的策略主要包括促进内源性β细胞的自我复制、诱导SC分化、将非β细胞重编程为β样细胞以及通过细胞干预生成胰腺样类器官。在这篇综述中,我们讨论了这些方法的当前最新技术,描述了相关的挑战,提出了潜在的解决方案,并强调了优化 β 细胞或胰岛移植和相关临床试验的持续努力。这些有效的细胞疗法将产生用于移植的功能性β细胞的可持续来源,并为未来的糖尿病治疗奠定坚实的基础。
The incidence of diabetes mellitus (DM) is steadily increasing annually, with 537 million diabetic patients as of 2021. Restoring diminished β cell mass or impaired islet function is crucial in treating DM, particularly type 1 DM. However, the regenerative capacity of islet β cells, which primarily produce insulin, is severely limited, and natural regeneration is only observed in young rodents or children. Hence, there is an urgent need to develop advanced therapeutic approaches that can regenerate endogenous β cells or replace them with stem cell (SC)-derived or engineered β-like cells. Current strategies for treating insulin-dependent DM mainly include promoting the self-replication of endogenous β cells, inducing SC differentiation, reprogramming non-β cells into β-like cells, and generating pancreatic-like organoids through cell-based intervention. In this Review, we discuss the current state of the art in these approaches, describe associated challenges, propose potential solutions, and highlight ongoing efforts to optimize β cell or islet transplantation and related clinical trials. These effective cell-based therapies will generate a sustainable source of functional β cells for transplantation and lay strong foundations for future curative treatments for DM.