Sackett Sara D, Rodriguez Aida, Odorico Jon S
Division of Transplantation, Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI 53711, USA.
Rev Diabet Stud. 2017 Spring;14(1):39-50. doi: 10.1900/RDS.2017.14.39. Epub 2017 Jun 12.
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions. Recent developments in beta-cell differentiation and genomic modifications are now propelling investigations into the mechanisms behind beta-cell failure and autoimmunity, and offer new strategies for reducing the propensity for immunogenicity. This review discusses the derivation of endocrine lineage cells from human pluripotent stem cells for the treatment of diabetes, and how the editing or manipulation of their genomes can transcend many of the remaining challenges of stem cell technologies, leading to superior transplantation and diabetes drug discovery platforms.
1型和2型糖尿病（T1D和T2D）是具有流行趋势的疾病，其由遗传、表观遗传、环境和生活方式选择等因素共同作用而变得复杂并得以界定。目前的治疗方法包括全胰腺或胰岛移植。然而，这些方法需要终身免疫抑制，且可用供体的稀缺使情况更加复杂。多能干细胞推动了干细胞生物学、药物开发、疾病建模和再生医学领域的研究，并且重要的是，它有助于对治疗干预措施进行探究。β细胞分化和基因组修饰方面的最新进展正在推动对β细胞功能衰竭和自身免疫背后机制的研究，并提供了降低免疫原性倾向的新策略。本综述讨论了从人类多能干细胞中衍生内分泌谱系细胞用于治疗糖尿病的方法，以及对其基因组进行编辑或操作如何能够克服干细胞技术中许多尚存的挑战，从而形成更优的移植和糖尿病药物发现平台。
