Diabetes mellitus is a metabolic disorder that affects more than 460 million people worldwide. Type 1 diabetes (T1D) is caused by autoimmune destruction of β-cells, whereas type 2 diabetes (T2D) is caused by a hostile metabolic environment that leads to β-cell exhaustion and dysfunction. Currently, first-line medications treat the symptomatic insulin resistance and hyperglycaemia, but do not prevent the progressive decline of β-cell mass and function. Thus, advanced therapies need to be developed that either protect or regenerate endogenous β-cell mass early in disease progression or replace lost β-cells with stem cell-derived β-like cells or engineered islet-like clusters. In this Review, we discuss the state of the art of stem cell differentiation and islet engineering, reflect on current and future challenges in the area and highlight the potential for cell replacement therapies, disease modelling and drug development using these cells. These efforts in stem cell and regenerative medicine will lay the foundations for future biomedical breakthroughs and potentially curative treatments for diabetes.

糖尿病是一种代谢疾病，影响全球超过 4.6 亿人。1 型糖尿病 (T1D) 是由 β 细胞的自身免疫破坏引起的，而 2 型糖尿病 (T2D) 是由导致 β 细胞衰竭和功能障碍的不利代谢环境引起的。目前，一线药物治疗症状性胰岛素抵抗和高血糖，但不能阻止β细胞质量和功能的进行性下降。因此，需要开发先进的疗法，以在疾病进展早期保护或再生内源性β细胞群，或用干细胞衍生的β样细胞或工程化胰岛样簇替换丢失的β细胞。在这篇评论中，我们讨论了干细胞分化和胰岛工程的最新技术，反思该领域当前和未来的挑战，并强调使用这些细胞进行细胞替代疗法、疾病建模和药物开发的潜力。这些在干细胞和再生医学方面的努力将为未来的生物医学突破和潜在的糖尿病治疗奠定基础。