4.1 Review

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

Journal

CURRENT OPINION IN ORGAN TRANSPLANTATION
Volume 15, Issue 1, Pages 79-85

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOT.0b013e3283344932

Keywords

beta-cells; diabetes; in-vivo regeneration; neogenesis; transdifferentiation

Funding

  1. Lundbeckfonden, Denmark [R7-A714-B576]
  2. JDRF [3-2009-683]
  3. National Institutes of Health (NIH/NIDDK)
  4. ADA

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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 P-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.

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