Sali Sujitha, Azzam Leen, Jaro Taraf, Ali Ahmed Ali Gebril, Mardini Ali, Al-Dajani Omar, Khattak Shahryar, Butler Alexandra E, Azeez Juberiya M, Nandakumar Manjula
King Abdullah University of Science and Technology (KAUST), Thuwal, 23955, Saudi Arabia.
Research Department, School of Postgraduate Studies & Research, Royal College of Surgeons in Ireland Bahrain, Adliya, 15503, Bahrain.
Stem Cell Res Ther. 2025 Mar 31;16(1):160. doi: 10.1186/s13287-025-04293-7.
The search for an effective cell replacement therapy for diabetes has driven the development of "perfect" pancreatic islets from human pluripotent stem cells (hPSCs). These hPSC-derived pancreatic islet-like β cells can overcome the limitations for disease modelling, drug development and transplantation therapies in diabetes. Nevertheless, challenges remain in generating fully functional and mature β cells from hPSCs. This review underscores the significant efforts made by researchers to optimize various differentiation protocols aimed at enhancing the efficiency and quality of hPSC-derived pancreatic islets and proposes methods for their improvement. By emulating the natural developmental processes of pancreatic embryogenesis, specific growth factors, signaling molecules and culture conditions are employed to guide hPSCs towards the formation of mature β cells capable of secreting insulin in response to glucose. However, the efficiency of these protocols varies greatly among different human embryonic stem cell (hESC) and induced pluripotent stem cell (hiPSC) lines. This variability poses a particular challenge for generating patient-specific β cells. Despite recent advancements, the ultimate goal remains to develop a highly efficient directed differentiation protocol that is applicable across all genetic backgrounds of hPSCs. Although progress has been made, further research is required to optimize the protocols and characterization methods that could ensure the safety and efficacy of hPSC-derived pancreatic islets before they can be utilized in clinical settings.
对糖尿病有效细胞替代疗法的探索推动了从人类多能干细胞（hPSC）生成“完美”胰岛的发展。这些源自hPSC的胰岛样β细胞可以克服糖尿病疾病建模、药物开发和移植治疗的局限性。然而，从hPSC生成功能完全且成熟的β细胞仍然存在挑战。本综述强调了研究人员为优化各种分化方案所做的重大努力，这些方案旨在提高源自hPSC的胰岛的效率和质量，并提出了改进方法。通过模拟胰腺胚胎发生的自然发育过程，利用特定的生长因子、信号分子和培养条件来引导hPSC形成能够响应葡萄糖分泌胰岛素的成熟β细胞。然而，这些方案在不同的人类胚胎干细胞（hESC）和诱导多能干细胞（hiPSC）系中的效率差异很大。这种变异性给生成患者特异性β细胞带来了特殊挑战。尽管最近取得了进展，但最终目标仍然是开发一种高效的定向分化方案，该方案适用于hPSC的所有遗传背景。尽管已经取得了进展，但在将源自hPSC的胰岛用于临床之前，仍需要进一步研究以优化能够确保其安全性和有效性的方案及表征方法。
