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Harvard scientists have developed a revolutionary new treatment for diabetes

Researchers have recently succeeded in treating type 1 diabetes by transplanting insulin-producing pancreatic cells into the patient.

University of Missouri scientists are partnering with Harvard and Georgia Tech to create a new diabetes treatment that involves transplanting insulin-producing pancreatic cells

It is estimated that type 1 diabetes affects about 1.8 million Americans. Although type 1 diabetes most often occurs in childhood or adolescence, it can occur in adulthood.

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Despite active research, there is no cure for type 1 diabetes. Treatment methods include taking insulin, monitoring your diet, controlling blood sugar levels, and exercising regularly. Scientists recently discovered a new treatment method that shows promise.

A group of researchers from the University of Missouri, 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 progress 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, MD, professor of child health, molecular microbiology and immunology at MU School of Medicine and one of the study’s lead authors, people with type 1 diabetes may experience dysfunction, self-targeting.

“The immune system is a tightly controlled defense mechanism that ensures the well-being of individuals in an environment full of infection,” Shirwan said. Type 1 diabetes develops when the immune system misidentifies and destroys the insulin-producing cells in the pancreas as an infection. Usually, once the perceived danger or threat is eliminated, the command and control mechanism of the immune system begins to eliminate any rogue cells. However, if this mechanism fails, diseases such as type 1 diabetes can emerge.”

Diabetes impairs 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 including heart disease, kidney damage, and vision loss.

Shirwan and Esma Yolko, professor of child health, molecular microbiology and immunology at MU School of Medicine, have spent the past two decades targeting the apoptosis mechanism that prevents “rogue” immune cells from causing diabetes or rejecting transplanted pancreatic islets by binding to a molecule called FasL on the surface of the islands.

“A type of programmed cell death occurs when a molecule called FasL interacts with another molecule called Fas on rogue immune cells, causing them to die,” said Yolko, one of the study’s first authors. “Therefore, our team pioneered technology that enabled a new form of FasL to be produced and presented to transplanted pancreatic islet cells or microgels to prevent their rejection by rogue cells. After transplantation of insulin-producing pancreatic islet cells, rogue cells move into the graft for destruction but are eliminated them by engaging FasL on their surface.”

Haval Shirvan and Isma Yolko Roy Planet NextGen . Building

Haval Sherwan and Esma Yolko work in their lab in the NextGen Precision Health Roy Planet building. Credit: University of Missouri

One advantage of this new method is the opportunity to forgo lifelong immunosuppressive drugs, which nullify the immune system’s ability to seek out and destroy a foreign body when introduced into the body, such as an organ, or in this case, a cell, an organ transplant.

“The main problem with immunosuppressive drugs is that they are not specific, so they can have a lot of adverse effects, such as higher cases of cancer,” Sherwan said. “So, using our technology, we’ve found a way that we can modify or train the immune system to accept, not reject, these transplanted cells.”

Their method uses technology embedded in a US patent filed by the University of Louisville and Georgia Tech and has since been licensed by a commercial company that has plans to pursue FDA approval for human testing. To develop the commercial product, MU researchers collaborated with Andres García and the team at Georgia Tech to attach FasL to the surface of microgels with demonstrated efficacy in a small animal model. Next, they joined forces with Jim Markmann and Ji Lei of Harvard University to evaluate the efficacy of the FasL-microgel technique in a large animal model, which is published in this study.

Haval Shirwan Microscope

Haval Shirwan looks at a sample through a microscope in his lab in the Roy Planet NextGen Precision Health building. Credit: University of Missouri

Incorporating the power of NextGen

This study represents a significant milestone in the bench-to-bed research process, or how laboratory findings are directly integrated into their use by patients to help treat various diseases and disorders, a hallmark of MU’s most ambitious research initiative, the NextGen Precision Health Initiative.

Highlighting the promise of personalized healthcare and the impact of multidisciplinary collaboration at scale, the NextGen Precision Health initiative brings together innovators such as Shirwan and Yolcu from across MU and the three other UM system research universities in pursuit of critical, life-changing health advances. . It is a collaborative effort to leverage MU’s research strengths toward a better future for the health of Missouri residents and beyond. The Roy Blunt NextGen Precision Health Building in MU anchors the comprehensive initiative and expands collaboration between researchers, clinicians and industry partners in a state-of-the-art research facility.

“I believe that by being in the right organization with access to a fantastic facility like the Roy Blunt NextGen Precision Health building, it will allow us to build on our current findings and take the necessary steps to continue our research and make the necessary improvements faster,” said Yolko.

Haval Shirwan and Asma Yolko

Haval Shirwan and Asma Yolko. Credit: University of Missouri

Shirwan and Yolko, who joined the faculty at MU in the spring of 2020, are part of the first group of researchers to begin work at the NextGen Precision Health Building and, after working at MU for nearly two years, are now among the first NextGen researchers to be accepted for a paper research paper and published in a peer-reviewed, high-impact academic journal.

Reference: “FasL microgels induce immune acceptance of islet allografts in non-human primates” by J. Lee, Maria M. Coronel, Esma S. ., 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 progress.
DOI: 10.1126 / sciadv.abm9881

Funding was provided through 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 Fellowship and a National Science Foundation Graduate Research Fellowship. The content is the sole responsibility of the authors and does not necessarily represent the official views of the funding agencies.

The study authors would also like to acknowledge Jessica Weaver, Lisa Kojima, Haley Tector, Kevin Ding, Rudi Matheson, and Nicholas Serivis for their artistic contributions.

Potential conflicts of interest were also noted. Three of the study’s authors, García, Shirwan, and Yolcu, are inventors in a US patent application filed by the University of Louisville and Georgia Tech Research Corporation (16/492441, filed February 13, 2020). Additionally, García and Shirwan are co-founders of iTolerance, and García, Shirwan, and Markmann serve on the iTolerance Scientific Advisory Board.