Recently, researchers have successfully treated type 1 diabetes by transplanting insulin-producing pancreatic cells into the patient.
Scientists at the University of Missouri are teaming up with Harvard and Georgia Tech to create a new treatment for diabetes that involves transplanting insulin-producing pancreatic cells.
Type 1 diabetes is estimated to affect about 1.8 million Americans. Although type 1 diabetes often develops during childhood or adolescence, it can occur in adulthood.
Despite active research, type 1 diabetes has no cure. Treatment methods include taking insulin, controlling your diet, monitoring your blood sugar levels, and exercising regularly. Scientists have also recently discovered a new method of treatment that is promising.
A group of researchers from the University of Missouri, the Georgia Institute of Technology and Harvard University have 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 on May 13th. His method includes transferring 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, Professor of Child Health and Molecular Microbiology and Immunology at MU School of Medicine and one of the lead authors of the study, the immune system of people with type 1 diabetes may malfunction. address yourself.
“The immune system is a tightly controlled defense mechanism that ensures the well-being of people in an environment full of infections,” Shirwan said. “Type 1 diabetes develops when the immune system misidentifies the pancreatic insulin-producing cells as infections and destroys them. Normally, once a perceived danger or threat is removed, the command and control mechanism of the immune system it activates to eliminate any rogue cell. However, if this mechanism fails, diseases such as type 1 diabetes can manifest. “
Diabetes affects the body’s ability to produce or use insulin, a hormone that helps regulate blood sugar metabolism. People with type 1 diabetes cannot control 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, professors of child health and molecular microbiology and immunology at MU School of Medicine, have spent the past two decades addressing a mechanism of apoptosis that prevents “difficult” immune cells from causing diabetes or rejection of pancreatic islets transplanted by adhesion. a molecule called FasL on the surface of the islets.
“A type of apoptosis occurs when a molecule called FasL interacts with another molecule called Fas on rogue immune cells, causing them to die,” said Yolcu, one of the study’s first authors. “Therefore, our team was a pioneer in a technology that allowed the production of a new form of FasL and its presentation in cells of transplanted pancreatic islets or microgels to avoid being rejected by rogue cells. After transplantation of insulin-producing pancreatic islet cells, the kidney cells are mobilized in the graft for destruction, but are removed by FasL, which involves Fas on its surface.
Haval Shirwan and Esma Yolcu work in their lab at the Roy Blunt NextGen Precision Health Building. Credit: University of Missouri
One of the advantages of this new method is the opportunity to potentially give up the life of taking immunosuppressive drugs, which counteract 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 main problem with immunosuppressive drugs is that they are not specific, so they can have many adverse effects, such as elevated cases of cancer development,” Shirwan said. “So using our technology, we found a way to modulate or train the immune system to accept, not reject, these transplanted cells.”
His method uses technology included in a U.S. patent filed by the University of Louisville and Georgia Tech and has since been authorized by a commercial company with plans to obtain FDA approval for human testing. To develop the commercial product, MU researchers collaborated with Andres Garcia and the Georgia Tech team to bind FasL to the surface of microgels with efficacy testing in a small animal model. They then teamed up 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 through a microscope in his laboratory in 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 how laboratory results are directly incorporated into patients’ use to help treat different diseases and disorders, a hallmark of the research initiative. MU’s most ambitious, NextGen Precision. Health initiative.
Highlighting 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 the MU and the other three research universities in the UM system to achieve life-changing precision health advances. . It is a collaborative effort to leverage the strengths of MU research toward a better future for the health of Missourians and beyond. MU’s Roy Blunt NextGen Precision Health Building underpins the global initiative and expands collaboration between researchers, physicians, and industry partners to the state-of-the-art research facility.
“I believe 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 make the improvements needed faster, “Yolcu said.
Haval Shirwan and Esma Yolcu. Credit: University of Missouri
Shirwan and Yolcu, who joined MU faculty in the spring of 2020, are part of the first group of researchers who began working at the NextGen Precision Health building, and after working at MU for nearly two years. , are now among the first researchers. from NextGen to accept and publish a peer-reviewed research journal in a high-impact academic journal.
Reference: “FasL microgels induce immune acceptance of islet allografts in nonhuman 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, May 13, 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 a graduate of the National Science Foundation. Research grant. The content is the sole responsibility of the authors and does not necessarily represent the official views of the funding agencies.
The study’s authors would also like to thank Jessica Weaver, Lisa Kojima, Haley Tector, Kevin Deng, Rudy Matheson, and Nikolaos Serifis for their technical contributions.
Possible conflicts of interest are also observed. Three of the study’s authors, Garcia, 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 Feb. 13). 2020). In addition, García and Shirwan are co-founders of iTolerance, and García, Shirwan and Markmann are part of the scientific advisory board of iTolerance.