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Are there pancreatic progenitor cells from which new islets form after birth?

Nature Clinical Practice Endocrinology & Metabolism volume 2, pages 240–241 (2006)Cite this article

Diabetes occurs when there is an inadequate functional mass of insulin-producing pancreatic β cells. Replacement of β cells by islet transplantation is a novel therapy for diabetes, although a major obstacle has been the limited amount of islet tissue available. A rigorous demonstration of the existence of postnatal pancreatic progenitor cells would clearly give focus to the development of innovative therapeutic techniques, including possibly stimulating formation of new endogenous β cells.

Throughout life, β-cell mass is dynamic with compensatory changes to meet demand and replenish the slow turnover of cells,1 suggesting either a capacity of β cells to regulate their mass and/or the presence of stem cells or progenitor cells that can differentiate into insulin-producing cells by the process of NEOGENESIS. In mice, rats, and humans the β-cell mass remains linear with body weight or BMI.2,3 The mass of β-cells increases by replication of existing β cells and increases in cell volume (hypertrophy). Additionally, islet neogenesis has long been assumed to contribute throughout much of life;1,2,3 however, a recent study by Dor et al.4 has challenged this assumption. The authors used lineage tracing of genetically marked β cells in mice, and concluded that no new β cells are formed from non-insulin-expressing stem cells or progenitor cells, either after birth or following 70% pancreatectomy. They suggest: “there is a time during embryonic development, or early postnatal life, at which the number of islets is set.” After this time, all new β cells are generated by replication of pre-existing β cells.4 The conclusions of this study have, nevertheless, been controversial and we have previously raised a number of criticisms,5 including the difficulty of definitively proving that something does not happen. Additionally, inherent problems of leakiness over time of CRE RECOMBINASE and inadequate sampling after birth and throughout the pancreas—particularly in newly regenerated lobes after partial pancreatectomy—might have biased the results.

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Acknowledgements

The research on which this viewpoint is based has been funded by the Juvenile Diabetes Research Foundation (grants to S Bonner-Weir and A Sharma), the NIH (S Bonner-Weir and the Joslin Diabetes Endocrine Research Center), and a group of generous donors. The authors appreciate the work and discussions with members of their groups, especially Drs Elena Toschi, Tandy Aye, Akari Inada, and Gordon Weir.

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  1. Joslin Diabetes Center and an Associate Professor of Medicine, Harvard Medical School,

    Susan Bonner-Weir & Arun Sharma

  2. Joslin Diabetes Center and an Assistant Professor of Medicine, Harvard Medical School, Boston, MA, USA

    Susan Bonner-Weir & Arun Sharma

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  1. Susan Bonner-Weir
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Correspondence to Susan Bonner-Weir.

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Bonner-Weir, S., Sharma, A. Are there pancreatic progenitor cells from which new islets form after birth?. Nat Rev Endocrinol 2, 240–241 (2006). https://doi.org/10.1038/ncpendmet0186

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