University of Missouri scientists are collaborating with Harvard and Georgia Tech to develop a new diabetes treatment that involves transplanting insulin-producing pancreatic cells
Type 1 diabetes affects an estimated 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 is not curable. Treatment methods include taking insulin, monitoring your diet, controlling blood sugar levels, and getting regular exercise. Scientists have also recently discovered a new promising treatment method.
A group of researchers from the University of Missouri, Georgia Institute of Technology and Harvard University has demonstrated the successful use of a novel type 1 diabetes treatment in a large animal model in a new study published in scientific advances on May 13th. Their method involves 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, a professor of child health and molecular microbiology and immunology at the MU School of Medicine and one of the study’s lead authors, the immune system of people with type 1 diabetes can malfunction, causing it to attack itself.
“The immune system is a tightly controlled defense mechanism that ensures the individual’s well-being in an environment teeming with infection,” Shirwan said. “Type 1 diabetes develops when the immune system mistakenly identifies the insulin-producing cells in the pancreas as an infection and destroys them. Normally, once a perceived danger or threat is eliminated, the immune system’s command and control mechanism kicks in to eliminate any rogue cells. However, when this mechanism fails, diseases such as type 1 diabetes can manifest themselves.”
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 don’t produce insulin. This lack of control can lead to life-threatening problems, including 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 last two decades targeting an apoptosis mechanism that prevents “malicious” immune cells from causing diabetes or the rejection of transplanted pancreatic islets by attaching a molecule called FasL to the surface of the islets.
“One type of apoptosis occurs when a molecule called FasL interacts with another molecule called Fas on renegade immune cells and causes them to die,” said Yolcu, one of the study’s first authors. “Therefore, our team pioneered a technology that enabled the production of a novel form of FasL and its presentation on transplanted pancreatic islet cells or microgels to prevent their rejection by rogue cells. After transplantation of insulin-producing pancreatic islet cells, rogue cells mobilize to the graft to destroy them, but are eliminated by FasL, which attacks Fas on their surface.”
An advantage of this new method is the possibility of potentially lifelong avoidance of taking immunosuppressive drugs that counteract the immune system’s ability to seek out and destroy a foreign object once it is introduced into the body, such as a foreign body. B. an organ or in this case a cell. Transplantation.
“The main problem with immunosuppressive drugs is that they are not specific, so they can have many side effects, such as B. a high number of cancers,” said Shirwan. “So, with our technology, we found a way to modulate or train the immune system to accept these transplanted cells and not reject them.”
Their method uses technology contained in a US patent filed by the University of Louisville and Georgia Tech, and has since been licensed by a commercial company planning 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 microgels, demonstrating efficacy in a small animal model. They then teamed up with Harvard’s Jim Markmann and Ji Lei to evaluate the effectiveness of FasL microgel technology in a large animal model that is published in this study.
Incorporating the power of NextGen
This study represents a significant milestone in the process of bench-to-bedside research, or how laboratory results flow directly into patient use to help treat various diseases and disorders, a hallmark of MU’s most ambitious research initiative, the NextGen Precision Health Initiative.
The NextGen Precision Health initiative underscores the promise of personalized healthcare and the impact of large-scale interdisciplinary collaboration, bringing together innovators like Shirwan and Yolcu from across MU and the three other research universities in the UM system to deliver life-changing advances in precision health achieve . It is a collaborative effort to leverage MU’s research strengths for a better future for the health of Missourians and beyond. The Roy Blunt NextGen Precision Health building at MU anchors the overall initiative and expands collaboration between researchers, clinicians and industry partners at the state-of-the-art research facility.
“I think when we are at the right institution with access to a great facility like the Roy Blunt NextGen Precision Health building, we can build on what we already have and take the steps necessary to advance our research and make the necessary improvements faster.” ‘ said Yolcu.
Shirwan and Yolcu, who joined MU’s faculty in Spring 2020, are part of the first research group to start work in the NextGen Precision Health building, and after working at MU for almost two years, they are now among the NextGen researchers to have a research paper accepted and published in a top peer-reviewed academic journal.
Reference: “FasL microgels induce immune acceptance of islet allografts in non-human primates” by Ji Lei, María M Coronel, Esma S Yolcu, Hongping Deng, Orlando Grimany-Nuno, Michael D Hunckler, Vahap Ulker, Zhihong Yang, Kang M 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 Andrés J García, May 13 2022, scientific advances.
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 Juvenile Diabetes Research Foundation postdoctoral fellowship and a National Science Foundation graduate research fellowship. The content is solely the responsibility of the authors and does not necessarily reflect the official opinion of the funding agencies.
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.
Potential conflicts of interest are also noted. Three of the study’s authors, García, Shirwan and Yolcu, are inventors in a US patent application (16/492441, filed February 13, 2020) filed by the University of Louisville and Georgia Tech Research Corporation. In addition, García and Shirwan are co-founders of iTolerance, and García, Shirwan and Markmann are members of iTolerance’s Scientific Advisory Board.