Type 1 diabetes: Tannic acid encapsulation protects transplanted islets from rejection

October 22, 2020

BIRMINGHAM, Ala. - Type 1 diabetes, or T1D, results from the autoimmune destruction of the insulin-producing cells of the pancreas. People with T1D require exogenous insulin and suffer swings in the levels of glucose in the blood that impact life expectancy and increase risks of cardiovascular disease, neuropathies and kidney failure.

One therapy is promising -- transplanting pancreatic islets from cadavers. But this requires immunosuppression, and reactivated autoimmunity leads to low graft viability and function after five years.

Now, a team of University of Alabama at Birmingham researchers has shown a simple way to protect transplanted islets, by coating them with a thin skin of alternating layers of two biopolymers. As reported in the journal Diabetes, this coating delays allograft and autoimmune-mediated rejection in mouse models of T1D.

"Our approach to inhibit proinflammatory immune responses with poly(N-vinylpyrrolidone)-tannic acid-encapsulated islets without systemic immunosuppression is a significant advancement toward successful islet transplants in humans," said senior authors Hubert Tse, Ph.D., and Eugenia Kharlampieva, Ph.D.

The biocompatible poly(N-vinylpyrrolidone)-tannic acid, or PVPON and tannic acid, or TA, are coated onto the islets in multiple alternating layers that are thin enough to allow oxygen and nutrients to easily reach the cells. This nano-thin encapsulation is about 120 times thinner than a sheet of plastic cling wrap. The key to its autoimmune protection, the UAB researchers say, are the layers of TA. This phenolic compound can scavenge reactive oxygen species and has an anti-inflammatory effect.

Oxidative stress from reactive oxygen species, or ROS, was already known to play a key role in the activation of alloreactive and autoreactive immunity toward engrafted islets, and the insulin-producing beta cells of the islets are more sensitive to ROS than many other cells of the body.

In autoimmune transplant experiments for the UAB study, more than half of the (PVPON/TA)-encapsulated grafts survived at 70 days post-transplant, while less than a quarter of the non-encapsulated grafts survived. In alloimmune transplant experiments, where the islets came from a different strain of mice, about 40 percent of the encapsulated grafts survived at 120 days post-transplant, while all of the unencapsulated grafts were rejected in less than 50 days.

In both types of transplantation, systemic immunosuppression was absent. The (PVPON/TA)-encapsulated islets maintained euglycemia significantly longer than non-encapsulated islets, and the grafts were immunomodulatory.

The mice receiving the encapsulated grafts had significant decreases in immune cell infiltration, ROS synthesis, inflammatory chemokines, cytokines and CD8 T cell infiltration, as compared to mice getting the non-encapsulated islets. ROS is known to promote proinflammatory M1 macrophages differentiation; in contrast, the mice receiving the encapsulated islets showed an increase in anti-inflammatory M2 macrophages.

Tse and Kharlampieva say much more can be done to improve immunosuppression by the encapsulation and extend that protection to other sources of islets that are more readily available than human cadaver islets.

"PVPON/TA coatings can be modified to increase the number of layers of PVPON and TA for encapsulation, complexed with immune inhibitory receptors, including CTLA-4, PD-L1, and/or anti-inflammatory cytokines like IL-10 and TGF-beta, to further enhance localized immunosuppression," they said. "The use of PVPON/TA coatings is not limited to encapsulation of human islets, as our preliminary studies also demonstrate that PVPON/TA encapsulation does not compromise neonatal porcine islet function and can also be expanded to include human stem cell-derived pancreatic beta-cells."
At UAB, Tse is an associate professor in the UAB Department of Microbiology, and Kharlampieva is a professor of chemistry in the UAB College of Arts and Sciences.

Co-authors with Tse and Kharlampieva for the Diabetes study, "Localized immunosuppression with tannic acid encapsulation delays islet allograft and autoimmune-mediated rejection," are Jessie M. Barra, UAB Department of Microbiology, and Veronika Kozlovskaya, Ph.D., UAB Department of Chemistry.

Support came from National Institutes of Health grants DK099550, T32.GM109780 and T32.GM008111; JDRF awards SRA-2016-270-S-B and 2-SRA-2019-692-S-B; and National Science Foundation grant NSF-DMR 1608728.

University of Alabama at Birmingham

Related Diabetes Articles from Brightsurf:

New diabetes medication reduced heart event risk in those with diabetes and kidney disease
Sotagliflozin - a type of medication known as an SGLT2 inhibitor primarily prescribed for Type 2 diabetes - reduces the risk of adverse cardiovascular events for patients with diabetes and kidney disease.

Diabetes drug boosts survival in patients with type 2 diabetes and COVID-19 pneumonia
Sitagliptin, a drug to lower blood sugar in type 2 diabetes, also improves survival in diabetic patients hospitalized with COVID-19, suggests a multicenter observational study in Italy.

Making sense of diabetes
Throughout her 38-year nursing career, Laurel Despins has progressed from a bedside nurse to a clinical nurse specialist and has worked in medical, surgical and cardiac intensive care units.

Helping teens with type 1 diabetes improve diabetes control with MyDiaText
Adolescence is a difficult period of development, made more complex for those with Type 1 diabetes mellitus (T1DM).

Diabetes-in-a-dish model uncovers new insights into the cause of type 2 diabetes
Researchers have developed a novel 'disease-in-a-dish' model to study the basic molecular factors that lead to the development of type 2 diabetes, uncovering the potential existence of major signaling defects both inside and outside of the classical insulin signaling cascade, and providing new perspectives on the mechanisms behind insulin resistance in type 2 diabetes and possibly opportunities for the development of novel therapeutics for the disease.

Tele-diabetes to manage new-onset diabetes during COVID-19 pandemic
Two new case studies highlight the use of tele-diabetes to manage new-onset type 1 diabetes in an adult and an infant during the COVID-19 pandemic.

Genetic profile may predict type 2 diabetes risk among women with gestational diabetes
Women who go on to develop type 2 diabetes after having gestational, or pregnancy-related, diabetes are more likely to have particular genetic profiles, suggests an analysis by researchers at the National Institutes of Health and other institutions.

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).

Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.

People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.

Read More: Diabetes News and Diabetes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.