Cellular pathways to beta-cell replacement.
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.
Fellous
Tariq G
TG
Centre for Diabetes and Metabolic Medicine, Queen Mary's School of Medicine and Dentistry, Institute of Cell and Molecular Science, 4 Newark Street, Whitechapel, London E1 2AT. t.g.fellous@qmul.ac.uk
Guppy
Naomi J
NJ
Brittan
Mairi
M
Alison
Malcolm R
MR
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000637:transplantation*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008648:Mesoderm / Q000502:physiology; D010179:Pancreas / Q000166:cytology; D033581:Stem Cell Transplantation