Department of Surgery, University of Alberta, Edmonton, AB T6G 2B7, Canada.
Department of Emergency Medicine, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada.
Cells. 2021 Jan 30;10(2):278. doi: 10.3390/cells10020278.
Over the last century, diabetes has been treated with subcutaneous insulin, a discovery that enabled patients to forego death from hyperglycemia. Despite novel insulin formulations, patients with diabetes continue to suffer morbidity and mortality with unsustainable costs to the health care system. Continuous glucose monitoring, wearable insulin pumps, and closed-loop artificial pancreas systems represent an advance, but still fail to recreate physiologic euglycemia and are not universally available. Islet cell transplantation has evolved into a successful modality for treating a subset of patients with 'brittle' diabetes but is limited by organ donor supply and immunosuppression requirements. A novel approach involves generating autologous or immune-protected islet cells for transplant from inducible pluripotent stem cells to eliminate detrimental immune responses and organ supply limitations. In this review, we briefly discuss novel mechanisms for subcutaneous insulin delivery and define their shortfalls. We describe embryological development and physiology of islets to better understand their role in glycemic control and, finally, discuss cell-based therapies for diabetes and barriers to widespread use. In response to these barriers, we present the promise of stem cell therapy, and review the current gaps requiring solutions to enable widespread use of stem cells as a potential cure for diabetes.
在过去的一个世纪里，糖尿病一直采用皮下胰岛素治疗，这一发现使患者免于因高血糖而死亡。尽管有新的胰岛素制剂，但糖尿病患者仍面临发病率和死亡率，给医疗保健系统带来了不可持续的成本。连续血糖监测、可穿戴胰岛素泵和闭环人工胰腺系统是一种进步，但仍未能重现生理性的正常血糖水平，并且并非普遍可用。胰岛细胞移植已发展成为治疗“脆性”糖尿病患者的一种成功方法，但受到供体器官供应和免疫抑制需求的限制。一种新方法涉及从诱导多能干细胞生成自体或免疫保护的胰岛细胞用于移植，以消除有害的免疫反应和器官供应限制。在这篇综述中，我们简要讨论了皮下胰岛素输送的新机制，并定义了它们的不足。我们描述了胰岛的胚胎发育和生理学，以更好地理解它们在血糖控制中的作用，最后讨论了用于糖尿病的基于细胞的治疗方法和广泛应用的障碍。针对这些障碍，我们提出了干细胞治疗的前景，并回顾了目前需要解决的差距，以实现干细胞的广泛应用，作为糖尿病的一种潜在治疗方法。
