University of Missouri researchers have used adult bone marrow stem cells along with a novel anti-inflammatory drug to cure type 1 diabetes in mice….
Habib Zaghouani, PhD, has spent years researching autoimmune disease at the MU School of Medicine with a focus on type 1 diabetes. His novel approach for the treatment of the disease uses adult stem cells and a modified immunoglobulin peptide to reduce pancreatic inflammation and extend the function of new beta cells within the pancreas.
Zaghouani’s previous research has developed Ig-GAD2, an immunoglobulin carrying glutamic acid decarboxylase (GAD) 206-220 peptide. When studied in hyperglycemic mice, Ig-GAD2 was able to reduce pancreatic inflammation and stimulate beta cell regeneration and slow type 1 diabetes progression. However the beta-cell regeneration was not sustainable leaving few viable cells unable to stop the eventual progression of the disease. Zaghouani’s latest study uses the addition of adult bone marrow stem cells to the Ig-GAD2 therapy to promote beta-cell regeneration and survival.
"We discovered that type 1 diabetes destroys not only insulin-producing cells but also blood vessels that support them," Zaghouani said. "When we realized how important the blood vessels were to insulin production, we developed a cure that combines a drug we created with adult stem cells from bone marrow. The drug stops the immune system attack, and the stem cells generate new blood vessels that help insulin-producing cells to multiply and thrive."
In mice with overt type 1 diabetes, Ig-GAD2 was given alongside healthy donor bone marrow stem cells injected into the pancreas to grow new beta cells. Zaghouani explains what they found, "The combination of Ig-GAD2 and bone marrow cells did result in production of new beta cells, but not in the way we expected. We thought the bone marrow cells would evolve directly into beta cells. Instead, the bone marrow cells led to growth of new blood vessels, and it was the blood vessels that facilitated reproduction of new beta cells. In other words, we discovered that to cure type 1 diabetes, we need to repair the blood vessels that allow the subject’s beta cells to grow and distribute insulin throughout the body."
It was concluded that reversing the progression of type 1 diabetes requires both suppression of immune driven inflammation and repair of the surrounding endothelial vessels to sustain newly formed beta cells. This methodology still requires trials in human tissue or subjects but if successful, Zaghouani and colleagues may have developed not only a potential cure for type 1 diabetes but other autoimmune disease as well.
X. Wan, F. B. Guloglu, A. M. VanMorlan, L. M. Rowland, S. Zaghouani, J. A. Cascio, M. Dhakal, C. M. Hoeman, H. Zaghouani. Recovery from Overt Type 1 Diabetes Ensues When Immune Tolerance and Cell Formation Are Coupled with Regeneration of Endothelial Cells in the Pancreatic Islets. Diabetes, 2013; DOI: 10.2337/db12-1281