Barinova Anna A, Bogomolova Alexandra Y, Bogomazova Alexandra N, Borisova Alyona A, Kiselev Sergey L, Panova Alexandra V
Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, Russia.
Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia.
Int J Mol Sci. 2025 Sep 8;26(17):8749. doi: 10.3390/ijms26178749.
Diabetes mellitus (DM) is a metabolic disease characterized by persistent hyperglycemia, resulting from defects in insulin secretion or impaired insulin action. In cases of severe pancreatic cell dysfunction and deficiency, the primary treatment remains lifelong insulin injections. A potential alternative is allogeneic pancreatic cell transplantation from a donor, which can stabilize glucose levels. However, the scarcity of donor material and the risk of immune rejection limit the widespread use of this approach. An alternative solution involves using in vitro-derived insulin-producing cells generated through the differentiation of pluripotent stem cells (PSCs), which could overcome the shortage of transplantable material. Furthermore, patient-specific cells-obtained directly from the patient via reprogramming of blood or skin cells into induced pluripotent stem cells (iPSCs)-would avoid immune rejection. Advances in this field have led to the active development and optimization of PSC differentiation into hormone-producing cells worldwide, with more than hundred patients dosed in clinical trials with ESC-derived cells and the single trial of iPSC-derived cells. This review highlights recent progress and prospects in generating insulin-producing cells from human PSCs, their applications in therapy development and disease modeling, as well as the current challenges and potential solutions.
糖尿病（DM）是一种以持续性高血糖为特征的代谢性疾病，由胰岛素分泌缺陷或胰岛素作用受损引起。在严重胰腺细胞功能障碍和缺乏的情况下，主要治疗方法仍然是终身注射胰岛素。一种潜在的替代方法是来自供体的同种异体胰腺细胞移植，它可以稳定血糖水平。然而，供体材料的稀缺和免疫排斥风险限制了这种方法的广泛应用。另一种解决方案是使用通过多能干细胞（PSC）分化产生的体外衍生胰岛素生成细胞，这可以克服可移植材料的短缺。此外，通过将血液或皮肤细胞重编程为诱导多能干细胞（iPSC）直接从患者获得的患者特异性细胞将避免免疫排斥。该领域的进展已促使全球积极开展PSC向激素生成细胞分化的研发和优化工作，已有超过百名患者接受了胚胎干细胞衍生细胞的临床试验给药，以及诱导多能干细胞衍生细胞的单次试验。本综述重点介绍了从人PSC生成胰岛素生成细胞的最新进展和前景、它们在治疗开发和疾病建模中的应用，以及当前的挑战和潜在解决方案。
