Harvard researchers have developed a new way to treat diabetes

Researchers have recently successfully treated type 1 diabetes by transplanting insulin-producing pancreatic cells into a patient.

Researchers at the University of Missouri, in partnership with Harvard and Georgia Tech, are developing a new treatment for diabetes that involves transplanting insulin-producing pancreatic cells.

Type 1 diabetes affects approximately 1.8 million Americans. Although type 1 diabetes usually occurs in childhood or adolescence, it can occur in adulthood.

Despite active research, type 1 diabetes cannot be cured. Treatments include taking insulin, controlling your diet, controlling your blood sugar, and exercising regularly. Scientists have recently discovered a promising new treatment.

A team of researchers from the University of Missouri, Georgia Institute of Technology and Harvard University have shown that they have successfully used a new method of treating type 1 diabetes in a large animal model. Science Advances May 13. Their method involves the transfer of insulin-producing pancreatic cells, called pancreatic islets, from a donor to a recipient without the need for long-term immunosuppressive drugs.

According to Hawal Shirvan, a professor of pediatric health and molecular microbiology and immunology at MU School of Medicine and one of the study’s co-authors, people with type 1 diabetes can have their own immune systems damaged and targeted.

“The immune system is a tightly controlled defense mechanism that ensures the well-being of people in an environment full of infections,” Shirvan said. “Type 1 diabetes occurs when the immune system misidentifies and destroys insulin-producing cells in the pancreas as an infection. Normally, once the perceived danger or danger has been eliminated, the command-and-control mechanism of the immune system is activated in various defective cells. However, if this mechanism does not work, 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 cannot control their blood sugar because they do not produce insulin. Lack of this control can lead to life-threatening problems, including heart disease, kidney damage, and vision loss.

Shirvan and Esma Yolchu, a professor of pediatric and molecular microbiology and immunology at MU School of Medicine, have been targeting apoptosis for the past two decades to prevent “bad” immune cells from developing diabetes or rejecting transplanted pancreatic islets. A molecule called FasL on the surface of the islands.

Yolchu, one of the first authors of the study, said, “A type of apoptosis occurs when a molecule called FasL interacts with another molecule in a false immune cell called Fas, and this leads to their death.” “Therefore, our team has pioneered a technology that allows us to produce a new type of FasL and show it to transplanted pancreatic islet cells or microgels. After transplanting insulin-producing pancreatic islet cells, the damaged cells are mobilized for transplantation to collapse, but FasL is destroyed by attracting Fas to their surface.

Haval Shirvan and Esma Passenger Roy Blunt NextGen building

Haval Shirvan and Esma Yolchu work in their laboratory at the Roy Blunt NextGen Precision Health building. Credit: University of Missouri

One of the advantages of this new method is the ability to refrain for life from the use of immunosuppressive drugs that interfere with the immune system’s ability to search for and destroy foreign objects when they enter the body. transplantation.

“The main problem with immunosuppressive drugs is that they are non-specific, so they can have many side effects, such as high rates of cancer,” Shirvan said. “So, using our technology, we have found a way to modulate or train the immune system by accepting these transplanted cells and not rejecting them.”

Their method uses technology patented by the U.S. University of Louisville and Georgia Tech, and has since been licensed by a commercial company that plans to have FDA approval for human testing. To develop a commercial product, MU researchers, in collaboration with a team of Andres Garcia and Georgia Tech, demonstrated the effectiveness of a small animal model by gluing FasL to the surface of microgels. They then joined Jim Markmann and J. Leigh of Harvard to evaluate the effectiveness of FasL-microgel technology in the large animal model published in this study.

Haval Shirvan microscope

Haval Shirvan is examining the sample under a microscope in the laboratory of Roy Blunt NextGen Precision Health. Credit: University of Missouri

Including the power of NextGen

This study represents an important stage in the research process from the chair to the bed, or the laboratory results are put into direct use by patients to help treat various ailments and diseases, a sign of MU’s most ambitious research initiative, NextGen Precision. Health Initiative.

Emphasizing the promise of personalized health care and the impact of large-scale interdisciplinary collaboration, the NextGen Precision Health Initiative seeks to bring together life-changing precision health by bringing together innovators such as Shirvan and Yolchu from three other MU and UM system research universities. . This is a joint effort to use the power of MU research towards a better future for the health of Missourians and beyond. The Roy Blunt NextGen Precision Health building at MU will strengthen the overall initiative and expand collaboration between researchers, clinics and industry partners at the state-of-the-art facility.

“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 the results of our research and take the necessary action, as well as make the necessary improvements faster,” Jolchu said.

Hawal Shirvan and Esma Yolchu

Hawal Shirvan and Esma Yolchu. Credit: University of Missouri

Shirvan and Yolchu, who joined MU in the spring of 2020, are part of the first group of researchers to start working at the NextGen Precision Health building and are now among the first to work after nearly two years at MU. A scientific article from NextGen was published in a highly influential, peer-reviewed academic journal.

Reference: Ji Lei, Maria M. Coronel, Esma S. Passenger, Honping Deng, Orlando Grimani-Nuno, Michael D. “FasL microgels stimulate the immune response of island allogrants in non-human primates” written by Hankler, Wahap Ulker, Jihong Yang, Kang M. Li, Alexander Zhang, Hao Luo, Cole W. Peters, Zhunglian Tzu, Tao Chen, Zhenjuan Wang, Collin S. McCoy, Ivy A. Rosales, James F. Markman, Hawal Shirvan, and Andres 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 Fellow. The content is the sole responsibility of the authors and does not represent the official views of the financial agencies.

The authors of the study also thank Jessica Weaver, Lisa Kojima, Haley Tector, Kevin Deng, Rudy Mateson and Nicholas Serifis for their technical contributions.

Possible conflicts of interest are also noted. The three authors of the study, Garcia, Shirvan and Yolku – the University of Louisville and the Georgia Technological Research Corporation (16/492441, dated February 13, 2020) are the inventors of the U.S. patent application. In addition, Garcia and Shirvan are co-founders of iTolerance, and Garcia, Shirvan and Markmann serve on the iTolerance Scientific Advisory Board.

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