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


RESULTS
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.


CONCLUSIONS
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.
Juhl
Kirstine
K
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
Bonner-Weir
Susan
S
Sharma
Arun
A
D000328:Adult; D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D053595:Embryonic Stem Cells / Q000637:transplantation; D015316:Genetic Therapy; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D046790:Pancreas, Exocrine / Q000378:metabolism / Q000473:pathology*; D012038:Regeneration; D023822:Tissue Engineering; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors