Cellular pathways to β‐cell replacement

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Abstract
In the twenty‐first century, diabetic patients are likely to be one of the major beneficiaries from the advancement of regenerative medicine through cellular therapies. Though the existence of a specific self‐renewing stem cell within the pancreas is still far from clear, a surprising variety of cells within the pancreas can differentiate towards a β‐cell phenotype: ductular cells, periductular mesenchymal cells and β‐cells themselves can all give rise to new β‐cells. Extra‐pancreatic adult somatic stem cells, in particular, those originating from bone marrow may also be capable of differentiating to β‐cells, though equally well the beneficial effects of bone marrow cells may reside in their contribution to the damaged islet vasculature. Forced expression of the β‐cell‐specific transcription factor Pdx1 in hepatocytes also holds promise as a therapeutic strategy to increase insulin levels in diabetic individuals. Embryonic stem (ES) cells are clearly another possible source for generating β‐cells, but ES cells are beyond the scope of this review, which focuses on adult stem and progenitor cells capable of producing β‐cells. Despite considerable endeavour, we still have much to learn in the field of pancreatic regeneration prior to any clinically applicable therapy based upon adult stem cells. Copyright © 2006 John Wiley & Sons, Ltd.

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