AbstractBone marrow transplantation has been reported
to alleviate toxin-induced diabetes in mice.
Nevertheless, the underlying mechanism is still
unclear. In the present study, we demonstrate
that a genetically labeled, monoclonal
hematopoietic stem cell line (seRM26 cells),
grafted into the pancreas of diabetic mice,
induces beta cell proliferation and activation of a
pancreatic endocrine progenitor cell marker,
Neurogenin-3 (Ngn3), resulting in a reproducible,
complete and permanent recovery from the
hyperglycemic state. The injected cells do not
differentiate to beta cells or their progenitors but
stimulate the recruitment and retention of
angiocompetent myeloid cells in a VEGF-A/SDF-
1-dependent manner. Specific inhibition of either
angiogenesis or inflammation revealed that
inflammatory neovascularization is a pivotal
process for endocrine progenitor activation and
beta cell proliferation. Local administration of
VEGF-A recapitulates the regenerative process in
up to half of the number of diabetic mice.
However, transplantation of the inflammatory
cells, isolated from the regenerating pancreas,
failed to do so, suggesting that recruited
inflammatory cells are necessary but not
sufficient to induce a full regenerative process.
Our finding opens perspectives towards a
treatment for diabetes by isogeneic bone marrow
transplantation and/or induction of
neovascularization in the injured pancreas.
|Date of Award||6 Jun 2011|
|Supervisor||Henry Heimberg (Promotor), Yuval Dor (Jury), Jody Haigh (Jury), Aernout Luttun (Jury), Karin Vanderkerken (Jury), Herman Tournaye (Jury), Ivan Van Riet (Promotor) & Kris Thielemans (Promotor)|