Regenerating pancreatic beta-cells: plasticity of adult pancreatic cells and the feasibility of in-vivo neogenesis

Curr Opin Organ Transplant. 2010 Feb;15(1):79-85. doi: 10.1097/MOT.0b013e3283344932.

Abstract

Purpose of review: Diabetes results from inadequate functional mass of pancreatic beta-cells and therefore replenishing with new glucose-responsive beta-cells is an important therapeutic option. In addition to replication of pre-existing beta-cells, new beta-cells can be produced from differentiated adult cells using in-vitro or in-vivo approaches. This review will summarize recent advances in in-vivo generation of beta-cells from cells that are not beta-cells (neogenesis) and discuss ways to overcome the limitations of this process.

Recent findings: Multiple groups have shown that adult pancreatic ducts, acinar and even endocrine cells exhibit cellular plasticity and can differentiate into beta-cells in vivo. Several different approaches, including misexpression of transcription factors and tissue injury, have induced neogenesis of insulin-expressing cells in vivo and ameliorated diabetes.

Summary: Recent breakthroughs demonstrating cellular plasticity of adult pancreatic cells to form new beta-cells are a positive first step towards developing in-vivo regeneration-based therapy for diabetes. Currently, neogenesis processes are inefficient and do not generate sufficient amounts of beta-cells required to normalize hyperglycemia. However, an improved understanding of mechanisms regulating neogenesis of beta-cells from adult pancreatic cells and of their maturation into functional glucose-responsive beta-cells can make therapies based on in-vivo regeneration a reality.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Animals
  • Cell Lineage*
  • Cell Proliferation*
  • Cell Transdifferentiation*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Diabetes Mellitus / therapy*
  • Embryonic Stem Cells / transplantation
  • Genetic Therapy
  • Humans
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology*
  • Insulin-Secreting Cells / transplantation
  • Pancreas, Exocrine / metabolism
  • Pancreas, Exocrine / pathology*
  • Regeneration*
  • Tissue Engineering*
  • Transcription Factors / metabolism

Substances

  • Transcription Factors