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Human embryonic stem cells as a source for cell replacement therapy in diabetes

Tuesday, 11 September, 2012 - 17:00
Campus: Brussels Health Campus
Faculty: Medicine and Pharmacy
auditorium P. Brouwer
Lina Sui
phd defence

Type 1 diabetes is characterized by the loss of beta cells in the pancreas.
Many possible ways of generating beta cells have been studied with the
intention to relieve the shortage of donor pancreata as transplantable
source to treat diabetes patients. Human embryonic stem cells (hESCs)
represent a promising source for cell replacement therapy in diabetes. The
generation of abundant functional beta cells from hESCs is not yet
achieved in vitro, although derivation of PDX1 expressing pancreatic
progenitor cells from hESCs in vitro and their differentiation potential
towards mature beta cells in vivo have been demonstrated. In our study,
we aimed at evaluating the potential of hESCs to be used as a source in
beta cell replacement therapy. We studied the further differentiation of
hESC-derived PDX1+ progenitors in vivo and their proliferation in a defined
medium in order to fulfill the vast demand for cell replacement therapy.
We also studied the signalling pathways that regulate definitive endoderm
(DE) differentiation with the aim of eliminating undefined factors present in
the culture media. We found that the PDX1+ progenitors have potential to
further differentiate into pancreatic endocrine cells after transplantation in
the subcutaneous space in mice. Furthermore, the pancreatic progenitors
can be expanded in a serum free proliferation medium. Finally, we
addressed the role of FGF signaling in the early stage of DE development.
In conclusion, our findings allowed us to derive fully specified pancreatic
progenitors in vitro and setup an efficient system for expansion of these
progenitors. They pave the way for using hESC-derived pancreatic
progenitors as a source in cell replacement therapy.

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