Cellular pathways to beta-cell replacement

Diabetes Metab Res Rev. 2007 Feb;23(2):87-99. doi: 10.1002/dmrr.692.

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 beta-cell phenotype: ductular cells, periductular mesenchymal cells and beta-cells themselves can all give rise to new beta-cells. Extra-pancreatic adult somatic stem cells, in particular, those originating from bone marrow may also be capable of differentiating to beta-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 beta-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 beta-cells, but ES cells are beyond the scope of this review, which focuses on adult stem and progenitor cells capable of producing beta-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.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Epithelial Cells / physiology
  • Humans
  • Insulin-Secreting Cells / transplantation*
  • Islets of Langerhans Transplantation / methods*
  • Mesoderm / physiology
  • Pancreas / cytology
  • Stem Cell Transplantation