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

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Abstract
Purpose of review Diabetes results from inadequate functional mass of pancreatic β-cells and therefore replenishing with new glucose-responsive β-cells is an important therapeutic option. In addition to replication of pre-existing β-cells, new β-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 β-cells from cells that are not β-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 β-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 β-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 β-cells required to normalize hyperglycemia. However, an improved understanding of mechanisms regulating neogenesis of β-cells from adult pancreatic cells and of their maturation into functional glucose-responsive β-cells can make therapies based on in-vivo regeneration a reality.