Generating ??-cells in vitro: Progress towards a Holy Grail

摘要

Purpose of Review: Diabetes is a debilitating disease characterized by a chronic inability to normalize blood glucose levels. Transplanting cadaveric pancreata or isolated pancreatic islets can restore glucose homeostasis, but organ demand outstrips supply. Consequently, there is significant interest in alternative tissue sources. This review summarizes state-of-the-art efforts to generate scalable, functional ??-cells to treat diabetes. Recent Findings: Applying knowledge gleaned from developmental biology, human pluripotent stem cells can be treated stepwise with combinations of small molecules, developmentally relevant growth factors, and morphogens to generate pancreatic progenitor cells (PPCs) in vitro. Transplanted PPCs can then further mature in vivo into functional islet-like tissues containing all of the endocrine hormone cells present in adult islets and can reverse hyperglycemia in a diabetic animal model. Recent publications demonstrate that skin, liver, and other cell lineages may also be reprogrammed to functional ??-like cells. Summary: Although generation of fully functional ??-cells in vitro has not yet been achieved, possible intermediate approaches to treat diabetes include using PPCs or reprogramming adult cells to ??-like cells. A cell therapy with either approach will require isolation from the host immune response. Ongoing efforts are addressing this need through the use of immune-isolation devices to avoid immunosuppressive drugs.