Recovery from Overt Type 1 Diabetes Ensues When Immune Tolerance and β Cell Formation Are Coupled with Regeneration of Endothelial Cells in the Pancreatic Islets
- Xiaoxiao Wan1,
- F. Betul Guloglu1,
- Amie M. VanMorlan2,
- Linda M. Rowland1,
- Sarah Zaghouani1,
- Jason A. Cascio1,
- Mermagya Dhakal1,
- Christine M. Hoeman1 and
- Habib Zaghouani1,2,3
- 1Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO, USA
- 2Department of Child Health, University of Missouri School of Medicine, Columbia, MO, USA.
- 3Department of Neurology, University of Missouri School of Medicine, Columbia, MO, USA.
- Corresponding author: Habib Zaghouani,
Immune modulation of pancreatic inflammation induces recovery from type 1 diabetes (T1D) but remission was not durable perhaps due to an inability to sustain the formation and function of new pancreatic β-cells. We have previously shown that Ig-GAD2, carrying glutamic acid decarboxylase (GAD) 206-220 peptide, induced in hyperglycemic mice immune modulation that was able to control pancreatic inflammation, stimulate β-cell regeneration and prevent T1D progression. Herein, we show that the same Ig-GAD2 regimen given to mice with overt T1D is unable to reverse the course of disease despite eradication of Th1 and Th17 cells from the pancreas. However, the regimen is able to sustain recovery from T1D when Ig-GAD2 was accompanied with transfer of bone marrow (BM) cells from healthy donors. Interestingly, alongside immune modulation there was concomitant formation of new β and endothelial cells in the pancreas. The new β-cells were of host origin while the donor BM cells gave rise to the endothelial cells. Moreover, transfer of purified BM endothelial progenitors instead of whole BM cells sustained both β and endothelial cell formation and reversal of diabetes. Thus, overcoming T1D requires both immune modulation and repair of the islet vascular niche to preserve newly formed β-cells.
- Received September 18, 2012.
- Accepted April 16, 2013.
- © 2013 by the American Diabetes Association.
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