In a new study, a team of researchers from the University of Missouri, Georgia Tech and Harvard University demonstrated the successful use of a new treatment for type 1 diabetes in a large animal model. Their approach involves transplanting insulin-producing pancreatic cells – so-called pancreatic islets – from donor to recipient, without the need for long-term immunosuppressive drugs.
In people living with type 1 diabetes, their immune systems can malfunction, causing it to attack itself, said Haval Shirvan, a professor of pediatric health and molecular microbiology and immunology at the MU School of Medicine and one of the lead authors of the study.
“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 develops when the immune system mistakenly identifies the pancreatic cells that produce insulin as an infection and destroys them. if this mechanism fails, diseases such as type 1 diabetes can occur. ”
Diabetes affects the body’s ability to produce or use insulin, a hormone that helps regulate how blood sugar is used in the body. People living with type 1 diabetes do not produce insulin and therefore cannot control their blood sugar. Such loss of control can lead to life-threatening complications such as heart disease, kidney and eye damage.
For the past two decades, Shirvan and Esma Yolku, a professor of pediatric health and molecular microbiology and immunology at MU Medical School, have focused on a mechanism called apoptosis that destroys “rogue” immune cells from diabetes or transplant rejection. islets of the pancreas by attaching a molecule called FasL to the surface of the islets.
“A type of apoptosis occurs when a molecule called FasL interacts with another molecule called Fas on immune immune cells, and this leads to their death,” said Yelku, one of the study’s first authors. “So our team started a technology that allowed us to produce a new form of FasL and present it on transplanted pancreatic islet cells or microgels to prevent them from being rejected by fake cells. After transplanting pancreatic islet cells that produce insulin-producing for destruction, but are eliminated when FasL draws Fas to their surface ”.
One of the benefits of this new method is the ability to potentially stop taking lifelong immunosuppressive drugs that prevent the immune system from searching for and destroying a foreign object when introduced into an 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 a lot of side effects, such as high rates of cancer,” Shirvan said. “So using our technology, we found a way to modulate or teach the immune system to accept rather than reject these transplanted cells.”
Their method uses technology included in a U.S. patent filed by the University of Louisville and the Georgia School of Technology, and has since been licensed by a commercial company that 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 attach FasL to the surface of microgels with evidence of efficacy in small animal models. They then teamed up with Jim Markman and Jay Leigh of Harvard to evaluate the effectiveness of FasL-microgel technology on a large animal model, which is published in this study.
Enable NextGen power
This study represents a significant milestone in bench-to-bed research or how laboratory results are directly incorporated into patients ’use to treat a variety of diseases and disorders, a hallmark of MU’s most ambitious research initiative, NextGen Precision. Health Initiative.
Emphasizing the prospects of personalized care 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 three other UM research universities in the pursuit of life-changing healthcare accuracy. . It is a collaborative effort to harness the research benefits of MU for a better future for the health of Missouri residents and beyond. The Roy Blunt NextGen Precision Health building at MU consolidates the overall initiative and expands collaboration between researchers, clinicians, and industry partners at a state-of-the-art research center.
“I think staying in the right facility with access to such a great facility as the Roy Blunt NextGen Precision Health building will allow us to build on our existing findings and take the necessary steps for further research as well as make the necessary improvements faster. “- said Yelka.
Shirvan and Yelku, who joined the MU faculty in the spring of 2020, are part of the first group of researchers to start working at the NextGen Precision Health building, and after nearly two years at MU they are among the first researchers from NextGen. that the research work be accepted and published in a peer-reviewed peer-reviewed scientific journal.
“FasL microgels induce immune uptake of islet allografts in non-human primates,” published in Advances in science, a journal published by the American Association for the Advancement of Science (AAAS). 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 Fellowship. The sole responsibility for the content lies with the authors and does not necessarily reflect the official views of the financial institutions.
Other study authors include Ji Lei, Hongping Deng, Zhihong Yang, Kang Li, Alexander Zhang, Cole Peters, Zhongliang Zou, Zhenjuang Wang, Ivy Rosales, and James Markman of Harvard; Michael Hankler and Andres J. Garcia at the Georgia Institute of Technology (Georgia Technology); Hao Luo at the Western Theater Command Main Hospital in Chengdu, China; Tao Chen at Xiamen University Medical School in Xiamen, China; and Colin McCoy of the Massachusetts Institute of Technology. The authors of the study would also like to thank Jessica Weaver, Lisa Kodima, Hailey Tector, Kevin Deng, Rudy Matheson and Nikolaas Serifis for their technical contributions.
Possible conflicts of interest are also noted. Three of the study’s authors, Garcia, Shirvan, and Yolku, are the inventors of a U.S. patent application filed by the University of Louisville and the Georgia Technical Research Corporation (16/492441, filed February 13, 2020). In addition, Garcia and Shirvan are co-founders of iTolerance, and Garcia, Shirvan and Markman are on the iTolerance Scientific Advisory Board.