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The use of stem cells for pancreatic regeneration in diabetes mellitus

Abstract

The endocrine pancreas represents an interesting arena for regenerative medicine and cell therapeutics. One of the major pancreatic diseases, diabetes mellitus is a metabolic disorder caused by having an insufficient number of insulin-producing β cells. Replenishment of β cells by cell transplantation can restore normal metabolic control. The shortage in donor pancreata has meant that the demand for transplantable β cells has outstripped the supply, which could be met by using alternative sources of stem cells. This situation has opened up new areas of research, such as cellular reprogramming and in vivo β-cell regeneration. Pluripotent stem cells seem to be the best option for clinical applications of β-cell regeneration in the near future, as these cells have been demonstrated to represent an unlimited source of functional β cells. Although compelling evidence shows that the adult pancreas retains regenerative capacity, it remains unclear whether this organ contains stem cells. Alternatively, specialized cell types within or outside the pancreas retain plasticity in proliferation and differentiation. Cellular reprogramming or transdifferentiation of exocrine cells or other types of endocrine cells in the pancreas could provide a long-term solution.

Key Points

  • Pancreatic progenitors can be derived from human embryonic stem cells and have the capacity to generate functional β cells after transplantation

  • Whether mesenchymal stem cells and other types of adult stem cells can generate functional β cells remains unclear

  • Some types of differentiated cells within the adult pancreas retain sufficient plasticity to transdifferentiate into β cells; the most promising examples are α cells and acinar exocrine cells

  • The available data on pancreatic β-cell regeneration and transdifferentiation have mainly been obtained in mouse models and still need to be reproduced in humans

  • The future success of transplantation of β cells derived from embryonic stem cells or regeneration of endogenous β cells depends on effective prevention of autoimmune and/or alloimmune rejection

  • The most promising strategy at the moment is transplantation of pancreatic progenitors (or β cells) derived from embryonic stem cells, as these are widely available and standard protocols already exist

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Figure 1: Current strategies for generating pancreatic (endocrine) progenitors from human pluripotent stem cells.
Figure 2: Candidate progenitor cells, from which pancreatic β cells could be derived.

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Acknowledgements

The authors' research was supported by the Research Foundation Flanders (FWO) and the European Union (FP7).

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Bouwens, L., Houbracken, I. & Mfopou, J. The use of stem cells for pancreatic regeneration in diabetes mellitus. Nat Rev Endocrinol 9, 598–606 (2013). https://doi.org/10.1038/nrendo.2013.145

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