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A Revolutionary Transplant for Type 1 Diabetes

Scientists of the University of Missouri have partnered with Georgia Institute of Technology and Harvard University for creating a novel treatment for Type 1 diabetes mellitus (DM) which involves transplanting insulin-producing Beta cells of the pancreas.

Type 1 DM often develops in childhood or adolescence, and treatment largely involves insulin (subcutaneous injections with or without oral hypoglycemic/antidiabetic tablets), diet modifications, and regular physical exercise. However, scientists have recently discovered a novel treatment method with promising potential. The study showed successful results in a large-scale in vitro trial using animal models. Results were published in the Science Advances journal on May 13, 2022. The treatment involves transferring insulin-producing pancreatic islets/cells, from a donor to a recipient and if proved efficacious in further trials, could partially or completely eliminate the need for long-term medications.

According to Dr. Haval Shirwan, Professor of Child Health and Molecular Microbiology and Immunology at the MU School of Medicine and one of the primary authors of the present study, in Type 1 diabetics, the immune system shows malfunctioning, leading it to target cells of self and destroy them.

Dr. Shirwan states, “The immune system is a tightly controlled defense mechanism that ensures the well-being of individuals in an environment full of infections. Type 1 diabetes develops when the immune system misidentifies the insulin-producing cells in the pancreas as infections 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, if this mechanism fails, diseases such as Type 1 diabetes can manifest.”

Diabetes impairs the ability of pancreatic cells to produce and/or utilize insulin. People with Type 1 DM are unable to manage their blood glucose levels themselves since their bodies don’t produce insulin. The lack of blood glucose control could lead to fatal consequences such as cardiovascular disorders, renal damage, and loss of vision.

Dr. Shirwan and Dr. Esma Yolcu spent the previous two decades targeting an apoptotic mechanism for preventing “rogue” immune system cells from causing DM or rejection of transplanted pancreatic cells. They did this by attaching of a molecule known as FS-7-associated surface antigen ligand (FasL) to the surface of the pancreatic islets after Fas-FasL interactions.

Dr. Yolcu, one of the study’s first authors said, “A type of apoptosis occurs when a molecule called FasL interacts with another molecule called Fas on rogue immune cells, and it causes them to die. 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 being rejected by rogue cells. Following insulin-producing pancreatic islet cell transplantation, rogue cells mobilize to the graft for destruction but are eliminated by FasL engaging Fas on their surface.”

A key advantage of the novel treatment is the probability to forgo taking immunosuppressive medications for a lifetime. Such medications counteract the immune system’s ability to seek and destroy a foreign object when introduced into the human body, such as a cell, organ, or transplant.

Dr. Shirwan said, “The major problem with immunosuppressive drugs is that they are not specific, so they can have a lot of adverse effects, such as high instances of developing cancer,” Shirwan said. So, using our technology, we found a way that we can modulate or train the immune system to accept, and not reject, these transplanted cells.”

The treatment has utilized technology included in the United States patent filed by the University of Louisville and Georgia Institute of Technology and has been licensed by a commercial company with plans to pursue FDA approval for conducting human trials. The team attached FasL to the surface of microgels with proven efficacy in a small animal model in a previous study. Subsequently, they assessed the efficacy of the FasL-microgel technology in a large animal model for the present study.

The treatment reflects a significant milestone in bench-to-bedside research, or how laboratory results are directly incorporated into use by patients to help treat different diseases and disorders, a hallmark of MU’s most ambitious research initiative, the NextGen Precision Health initiative.

Reference:

FasL microgels induce immune acceptance of islet allografts in nonhuman 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, 13 May 2022, Science Advances. DOI: 10.1126/sciadv.abm9881

Author

Pooja Toshniwal Paharia

Dr. Pooja Toshniwal Paharia is a Consultant Oral and Maxillofacial Physician and Radiologist, M.DS (Oral Medicine and Radiology) from Mumbai. She strongly believes in evidence-based radiodiagnosis and therapeutic regimens for benign, potentially malignant, or malignant lesions and conditions either arising from the oral and maxillofacial structures or manifesting in the associated regions.

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