University of Missouri scientists work with Harvard and Georgia Tech to develop a new treatment for diabetes that involves insulin-producing pancreatic cell transplants Type 1 diabetes is estimated to affect approximately 1.8 million Americans. Although type 1 diabetes often develops in childhood or adolescence, it can also occur in adulthood. Despite active research, type 1 diabetes has no cure. Treatments include taking insulin, monitoring your diet, managing your blood sugar levels, and exercising regularly. Scientists have also recently discovered a promising new treatment method. A team of researchers from the University of Missouri, the Georgia Institute of Technology and Harvard University has demonstrated the successful use of a new treatment for type 1 diabetes in a large animal model in a new study published in Science Advances May 13. Their method involves the transfer of insulin-producing pancreatic cells, known as pancreatic islets, from a donor to a recipient without the need for long-term immunosuppressive drugs. According to Haval Shirwan, a professor of child health and molecular microbiology and immunology at the MU School of Medicine and one of the study’s lead authors, people with type 1 diabetes can malfunction, leading to self-targeting. “The immune system is a tightly controlled defense mechanism that ensures the well-being of individuals in an environment full of infections,” Shirwan said. “Type 1 diabetes develops when the immune system mistakenly recognizes the cells that produce insulin in the pancreas as infections and destroys them. Normally, as soon as a perceived danger or threat is eliminated, the immune system’s command and control mechanism begins to eliminate any rogue cells. However, if this mechanism fails, diseases such as type 1 diabetes can develop. “ Diabetes impairs the body’s ability to produce or use insulin, a hormone that helps regulate blood sugar metabolism. People with type 1 diabetes can not manage their blood sugar levels because they do not produce insulin. This lack of control can lead to life-threatening problems such as heart disease, kidney damage and vision loss. Shirwan and Esma Yolcu, a professor of child health and molecular microbiology and immunology at the MU School of Medicine, have spent the past two decades targeting an apoptosis mechanism that prevents “rogue” immune cells from causing diabetes or rejection of transplanted grafts. called FasL on the surface of the islets. “One type of apoptosis occurs when a molecule called FasL interacts with another molecule called Fas in rogue cells of the immune system and causes death,” said Yolcu, one of the study’s first authors. “Therefore, our team pioneered a technology that allowed the production of a new form of FasL and its introduction into transplanted pancreatic islet cells or microgels to prevent rejection by rogue cells. “After the transplantation of insulin-producing pancreatic islet cells, the ruthless cells are mobilized into the graft for destruction, but are eliminated by the FasL that involves Fas on their surface.” Haval Shirwan and Esma Yolcu work in their lab at the Roy Blunt NextGen Precision Health building. Credit: University of Missouri An advantage of this new method is the opportunity to give up a lifetime of taking immunosuppressive drugs, which neutralize the immune system’s ability to seek out and destroy a foreign object when it is introduced into the body, such as an organ, or in this case , a cell, transplant. “The most important problem with immunosuppressive drugs is that they are not specific, so they can have a lot of side effects, such as high rates of cancer,” Shirwan said. “So, using our technology, we found a way to shape or train the immune system to accept rather than reject these transplanted cells.” Their method uses technology contained in a U.S. patent filed by the University of Louisville and Georgia Tech and has since been licensed by a trading company with plans to seek FDA approval for human testing. To develop the commercial product, MU researchers worked with Andres García and the Georgia Tech team to attach FasL to the surface of the microgels, proving their effectiveness in a small animal model. They then collaborated with Jim Markmann and Ji Lei of Harvard to evaluate the effectiveness of FasL-microgel technology in a large animal model, which is published in this study. Haval Shirwan looks at a sample under a microscope in his lab at the Roy Blunt NextGen Precision Health Building. Credit: University of Missouri
Incorporating the power of NextGen
This study represents an important milestone in the process of bench-to-bed research or the way in which laboratory results are integrated directly into patients’ use to help treat various diseases and disorders, characteristic of his most ambitious research initiative. MU, NextGen Precision Health Initiative. Underlining the promise of personalized healthcare and the impact of large-scale interdisciplinary collaboration, the NextGen Precision Health initiative brings together innovators such as Shirwan and Yolcu from across MU and the other three UM Systems they change lives. It is a collective effort to harness MU’s research potential for a better future for the health of the people of Missouri and beyond. The Roy Blunt NextGen Precision Health building at MU anchors the overall initiative and extends collaboration between researchers, clinicians and industry associates to the state-of-the-art research facility. “I think that being in the right institution with access to a great facility like the Roy Blunt NextGen Precision Health building will allow us to build on our existing findings and take the necessary steps to advance our research and necessary improvements, faster “, said Yolcu. Haval Shirwan and Esma Yolcu. Credit: University of Missouri Shirwan and Yolcu, who joined the school at MU in the spring of 2020, are part of the first group of researchers who started working at the NextGen Precision Health building and after working at the MU for almost two years, are now among the first researchers from NextGen to accept a research paper and publish it in a high-profile, peer-reviewed academic journal. Reference: “FasL microgels induce immune acceptance of islet allografts in non-human primates” by Ji Lei, Maria M. Coronel, Esma S. Yolcu, Hongping Deng, Orlando Grimany-Nuno, Michael D. Hunckler, Vahap Ulker, Zhihong Yang , Kang M., et al Lee, Alexander Zhang, Hao Luo, Cole W. Peters, Zhongliang Zou, Tao Chen, Zhenjuan Wang, Colleen S. McCoy, Ivy A. Rosales, James F. Markmann, Haval Shirwan and Andrew J. Garcia, 13 May 2022, Science Advances.DOI: 10.1126 / sciadv.abm9881 Funding was provided by grants from the Juvenile Diabetes Research Foundation (2-SRA-2016-271-SB) and the National Institutes of Health (U01 AI132817) as well as a postdoctoral fellowship from the Juvenile Diabetes Research Foundation and Research Foundation Scholarship. The content is the sole responsibility of the authors and does not necessarily represent the official views of the funding bodies. The study authors would also like to thank Jessica Weaver, Lisa Kojima, Haley Tector, Kevin Deng, Rudy Matheson and Nikolaos Serifis for their technical contributions. There are also potential conflicts of interest. Three of the study’s authors, García, Shirwan, and Yolcu, are the inventors of a U.S. patent application filed by the University of Louisville and the Georgia Tech Research Corporation (16/492441, filed February 13, 2020). . In addition, García and Shirwan are co-founders of iTolerance and García, Shirwan and Markmann serve on the iTolerance Scientific Advisory Board.
