Stem Cell Reviews and Reports ( IF 4.8 ) Pub Date : 2020-08-26 , DOI: 10.1007/s12015-020-10018-5 Mitchell H Maloy 1 , Matthew A Ferrer 1 , Natesh Parashurama 1, 2, 3
Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from the loss of the pancreatic β-cells. The autoimmune destruction of the β-cells causes the loss of insulin production from the islets of the pancreas, resulting in the loss of blood glucose regulation. This loss of regulation, if not treated, can lead to a plethora of long-term complications in patients. Subsequently, T1DM patients rely on the administration of exogenous insulin sources to maintain their blood glucose levels. In this review, we summarize the history of T1DM therapy and current treatment options. Although treatments for T1DM have progressed substantially, none of the available treatment options allow the patient to live autonomously. Therefore, the challenge to develop a therapy that will fully reverse the disease still remains. A promising field of T1DM therapies is cell replacement therapies derived from human pluripotent stem cells. Here, we specifically review studies that employ stem-cell derived pancreatic progenitors transplanted for in vivo differentiation/maturation and discuss, in detail, the complications that arise post transplantation, including heterogeneity, graft immaturity, and host foreign bodyresponse. We also discuss efforts to induce human stem cell-derived mature β-cells in vitro and compare strategies regarding transplantation of pancreatic progenitors versus mature β-cells cells. Finally, we review key approaches that address critical limitations of in vivo progenitor differentiation including vascularization, oxygenation, and transplant location. The field of islet replacement therapy has made tremendous progress in the last two decades. If the strengths and limitations of the field continue to be identified and addressed, future studies will lead to an ideal treatment for T1DM.
中文翻译:
干细胞衍生的人类胰腺祖细胞的体内分化治疗 1 型糖尿病。
1 型糖尿病 (T1DM) 是一种自身免疫性疾病,由胰腺 β 细胞丢失引起。β 细胞的自身免疫性破坏会导致胰岛产生胰岛素的丧失,从而导致血糖调节功能丧失。如果不治疗,这种调节的丧失会导致患者出现过多的长期并发症。随后,T1DM 患者依靠使用外源性胰岛素来维持血糖水平。在这篇综述中,我们总结了 T1DM 治疗的历史和当前的治疗选择。尽管 T1DM 的治疗取得了实质性进展,但没有一种可用的治疗方案能让患者自主生活。因此,开发一种能够完全逆转疾病的疗法的挑战仍然存在。T1DM 疗法的一个有前景的领域是源自人类多能干细胞的细胞替代疗法。在这里,我们特别回顾了使用移植干细胞来源的胰腺祖细胞的研究体内分化/成熟并详细讨论移植后出现的并发症,包括异质性、移植物不成熟和宿主异物反应。我们还讨论了在体外诱导人类干细胞衍生的成熟 β 细胞的努力,并比较了有关移植胰腺祖细胞与成熟 β 细胞的策略。最后,我们回顾了解决体内祖细胞分化的关键限制的关键方法,包括血管化、氧合和移植位置。在过去的二十年里,胰岛替代疗法领域取得了巨大的进步。如果继续确定和解决该领域的优势和局限性,未来的研究将导致 T1DM 的理想治疗方法。