Abstract
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.
Highlights
There remains an urgent and critical need for new treatments for type 1 diabetes (T1D)
The development of in vitro generated populations of insulin-producing, glucose-responsive cells has overcome many significant challenges, including generation of chemically defined conditions for reproducibly differentiating Human embryonic stem cells (hESCs) into endocrine precursors (EPs) and, the development of strategies to purify these precursor cells to avoid the development of benign tumors such as teratomas
Kemp and colleagues demonstrated that direct injection of freshly isolated pancreatic islets into the portal vein of rats with streptozotocin-induced diabetes was able to restore normoglycemia [2]
Summary
There remains an urgent and critical need for new treatments for type 1 diabetes (T1D). BMP-7 (bone morphogenic protein 7) was found to induce conversion of human adult pancreatic nonendocrine pancreatic tissue into endocrine-like cells with elevated insulin content and that were glucose responsive in vitro and after transplantation. The first study demonstrating functional and meaningful secretion of insulin after transplantation into mice of βcells generated from hESC was published in 2008 [34], less than 10 years after the initial reports on spontaneous in vitro differentiation of hESC into insulin producing cells [35].
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