McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Department of Physiology, University of Toronto, Toronto, ON, Canada.
Front Endocrinol (Lausanne). 2021 Feb 25;12:636182. doi: 10.3389/fendo.2021.636182. eCollection 2021.
Restoring the number of glucose-responsive β-cells in patients living with diabetes is critical for achieving normoglycemia since functional β-cells are lost during the progression of both type 1 and 2 diabetes. Stem cell-derived β-cell replacement therapies offer an unprecedented opportunity to replace the lost β-cell mass, yet differentiation efficiencies and the final yield of insulin-expressing β-like cells are low when using established protocols. Driving cellular proliferation at targeted points during stem cell-derived pancreatic progenitor to β-like cell differentiation can serve as unique means to expand the final cell therapeutic product needed to restore insulin levels. Numerous studies have examined the effects of β-cell replication upon functionality, using primary islets and mouse models , yet studies that focus on proliferation in stem cell-derived pancreatic models are only just emerging in the field. This mini review will discuss the current literature on cell proliferation in pancreatic cells, with a focus on the proliferative state of stem cell-derived pancreatic progenitors and β-like cells during their differentiation and maturation. The benefits of inducing proliferation to increase the final number of β-like cells will be compared against limitations associated with driving replication, such as the blunted capacity of proliferating β-like cells to maintain optimal β-cell function. Potential strategies that may bypass the challenges induced by the up-regulation of cell cycle-associated factors during β-cell differentiation will be proposed.
恢复糖尿病患者中葡萄糖反应性β细胞的数量对于实现正常血糖水平至关重要，因为在 1 型和 2 型糖尿病的进展过程中功能性β细胞会丢失。基于干细胞的β细胞替代疗法为替代丢失的β细胞提供了前所未有的机会，然而，当使用既定方案时，胰岛素表达β样细胞的分化效率和最终产量都很低。在干细胞衍生的胰腺祖细胞向β样细胞分化的特定时间点驱动细胞增殖，可以作为扩大恢复胰岛素水平所需的最终细胞治疗产品的独特手段。许多研究已经使用原代胰岛和小鼠模型检查了β细胞复制对功能的影响，但是在干细胞衍生的胰腺模型中专注于增殖的研究在该领域才刚刚出现。这篇迷你综述将讨论关于胰腺细胞增殖的当前文献，重点介绍在其分化和成熟过程中干细胞衍生的胰腺祖细胞和β样细胞的增殖状态。与驱动复制相关的限制因素相比，诱导增殖以增加β样细胞的最终数量的益处将进行比较，例如增殖β样细胞维持最佳β细胞功能的能力减弱。将提出可能绕过β细胞分化过程中细胞周期相关因子上调引起的挑战的潜在策略。
