Hayek Alberto, King Charles C
Scripps Whittier Diabetes Institute, La Jolla, CA 92037 USA.
Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA 92093 USA.
Clin Diabetes Endocrinol. 2016 Feb 25;2:4. doi: 10.1186/s40842-016-0023-y. eCollection 2016.
Human embryonic stem cells (hESCs) and induced pluripotent cells (iPSCs) have the potential to differentiate into any somatic cell, making them ideal candidates for cell replacement therapies to treat a number of human diseases and regenerate damaged or non-functional tissues and organs. Key to the promise of regenerative medicine is developing standardized protocols that can safely be applied in patients. Progress towards this goal has occurred in a number of fields, including type 1 diabetes mellitus (T1D). During the past 10 years, significant technological advances in hESC/iPSC biochemistry have provided a roadmap to generate sufficient quantities of glucose-responsive, insulin-producing cells capable of eliminating diabetes in rodents. Although many of the molecular mechanisms underlying the genesis of these cells remain to be elucidated, the field of cell-based therapeutics to treat T1D has advanced to the point where the first Phase I/II trials in humans have begun. Here, we provide a concise review of the history of cell replacement therapies to treat T1D from islet transplantations and xenotranplantation, to current work in hESC/iPSC. We also highlight the latest advances in efforts to employ insulin-producing, glucose-responsive β-like cells derived from hESC as therapeutics.
人类胚胎干细胞（hESCs）和诱导多能干细胞（iPSCs）有分化为任何体细胞的潜力，这使它们成为细胞替代疗法治疗多种人类疾病以及再生受损或无功能组织和器官的理想候选者。再生医学前景的关键在于开发能够安全应用于患者的标准化方案。在包括1型糖尿病（T1D）在内的多个领域，朝着这一目标已经取得了进展。在过去十年中，hESC/iPSC生物化学领域的重大技术进步为生成足够数量的能够消除啮齿动物糖尿病的葡萄糖反应性、胰岛素分泌细胞提供了路线图。尽管这些细胞生成背后的许多分子机制仍有待阐明，但治疗T1D的基于细胞的疗法领域已经发展到人类首次I/II期试验已经开始的阶段。在这里，我们简要回顾从胰岛移植和异种移植到hESC/iPSC当前工作的治疗T1D的细胞替代疗法的历史。我们还强调了将源自hESC的胰岛素分泌、葡萄糖反应性β样细胞用作治疗方法的最新进展。
