Beta cell regeneration and normoglycemia restoration in diabetic mice through myeloid celldriven angiogenesis

Scriptie/masterproef: Doctoral Thesis


Bone 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.
Datum Prijs6 jun 2011
Toekennende instantie
  • Vrije Universiteit Brussel
BegeleiderHenry Heimberg (Promotor), Kris Thielemans (Jury), Karin Vanderkerken (Jury), Herman Tournaye (Jury), Ivan Van Riet (Jury), Yuval Dor (Jury), Jody Haigh (Jury) & Aernout Luttun (Jury)

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