Human β- cell regeneration: progress, hurdles, and controversy

Purpose of reviewTherapies that increase functional -cell mass may be the best long-term treatment for diabetes. Significant resources are devoted toward this goal, and progress is occurring at a rapid pace. Here, we summarize recent advances relevant to human -cell regeneration.Recent findingsNew -cells arise from proliferation of pre-existing -cells or transdifferentiation from other cell types. In addition, dedifferentiated -cells may populate islets in diabetes, possibly representing a pool of cells that could redifferentiate into functional -cells. Advances in finding strategies to drive -cell proliferation include new insight into proproliferative factors, both circulating and local, and elements intrinsic to the -cell, such as cell cycle machinery and regulation of gene expression through epigenetic modification and noncoding RNAs. Controversy continues in the arena of generation of -cells by transdifferentiation from exocrine, ductal, and alpha cells, with studies producing both supporting and opposing data. Progress has been made in redifferentiation of -cells that have lost expression of -cell markers.SummaryAlthough significant progress has been made, and promising avenues exist, more work is needed to achieve the goal of -cell regeneration as a treatment for diabetes.