title: Human β-cell regeneration: progress, hurdles, and controversy.
abstract: OBJECTIVE
  Therapies that increase functional β-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 β-cell regeneration.
  
  
  RESULTS
  New β-cells arise from proliferation of pre-existing β-cells or transdifferentiation from other cell types. In addition, dedifferentiated β-cells may populate islets in diabetes, possibly representing a pool of cells that could redifferentiate into functional β-cells. Advances in finding strategies to drive β-cell proliferation include new insight into proproliferative factors, both circulating and local, and elements intrinsic to the β-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 β-cells by transdifferentiation from exocrine, ductal, and alpha cells, with studies producing both supporting and opposing data. Progress has been made in redifferentiation of β-cells that have lost expression of β-cell markers.
  
  
  CONCLUSIONS
  Although significant progress has been made, and promising avenues exist, more work is needed to achieve the goal of β-cell regeneration as a treatment for diabetes.
authors.affiliation: University of Massachusetts Medical School, Diabetes Center of Excellence, Worcester, Massachusetts, USA.
authors.forename: Agata
authors.initials: A
authors.lastname: Jurczyk
authors.forename: Rita
authors.initials: R
authors.lastname: Bortell
authors.forename: Laura C
authors.initials: LC
authors.lastname: Alonso
mesh_terms: D060846:Cell Engineering; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology / Q000637:transplantation; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism; D012038:Regeneration
chemical_list: D009414:Nerve Growth Factors; C510637:VGF protein, human