DRC & Research News

This page shares the latest news in T1D research and DRC’s community.

Get the most recent diabetes research news, delivered straight to your inbox

Enhancing Protection for Islets

Enhancing Protection for Islets Following Transplantation

One treatment approach for type 1 diabetes that researchers have been experimenting with and refining for more than 20 years is islet transplantation. The goal is to take insulin-producing islets from cadavers (or another source) and transplant them into individuals with type 1 diabetes so that these cells will thrive and allow the body to begin producing insulin once again.

A common challenge with this approach is protecting the cells from immune system attack or cell death from lack of oxygen. A recent study has found a way to overcome some of these obstacles by encapsulating the islets in a jelly-like substance made of collagen. This helps create a scaffolding that will not initiate an immune response yet contains the islets while allowing them to grow new blood vessels that will ultimately provide them with oxygen. Since this blood vessel regrowth can take time, the researchers also injected the scaffolding with calcium peroxide. As the calcium peroxide breaks down, it releases oxygen which is used to keep the cells alive as they settle in and begin working.

In traditional organ transplantation, the organ is surgically connected to the circulatory system meaning that the organ automatically begins receiving the oxygen and nutrients it needs for survival. Islet transplants do not work this way since the cells are not a solid organ. In addition, the cells are typically injected into the liver rather than the pancreas where they would normally occur. There is a greater risk of the pancreas having a negative reaction and destroying the islets than the liver.

The researchers tested this new bioscaffold in diabetic mice. Some mice received islets on their own, some received islets in the bioscaffold, and some received islets and calcium peroxide in the bioscaffold. The diabetic mice who received the islets and calcium peroxide demonstrated greater blood glucose control over four weeks than the other two groups. The team is now looking at the possibility of injecting the scaffolding with stem cells as well to further enhance islet survival and function.

These types of advancements in treatment are encouraging when it comes to type 1 diabetes. It is expected that the U.S. Food and Drug Administration (FDA) will approve islet transplantation as a valid treatment for T1D, rather than an experimental treatment, this year. This could increase the number of options available to patients for effectively managing the disease.

Diabetes Research Connection continues to stay abreast of changes in the field and provides critical funding for early-career scientists pursuing novel research around T1D. Learn more about current projects and how to support these efforts by visiting https://diabetesresearchconnection.org.

Learn More +
Protein Sheild

Protein That Repels Immune Cells Protects Transplanted Pancreatic Islets From Rejection

Protein SheildTransplanting islets encapsulated with CXCL12 restores blood sugar control without immunosuppression in animal models of diabetes

An approach developed by Massachusetts General Hospital (MGH) investigators may provide a solution to the limitations that have kept pancreatic islet transplantation from meeting its promise as a cure for type 1 diabetes. In the March issue of the American Journal of Transplantation, the research team reports that encapsulating insulin-producing islets in gel capsules infused with a protein that repels key immune cells protected islets from attack by the recipient’s immune system without the need for immunosuppressive drugs, restoring long-term blood sugar control in mouse models. The technique was effective both for islets from unrelated mice and for islets harvested from pigs.

“Protecting donor islets from the recipient’s immune system is the next big hurdle toward making islet transplantation a true cure for type 1 diabetes,” says Mark Poznansky, MD, PhD, director of the MGH Vaccine and Immunotherapy Center, who led the study. “The first was generating enough insulin-producing islets, which has been addressed by several groups using pig islets or – as announced last fall by Doug Melton’s team at the Harvard Stem Cell Institute – with islet cells derived from human stem cells. Now our technology provides a way to protect islets or other stem-cell-derived insulin-producing cells from being destroyed as soon as they are implanted into a diabetic individual without the need for high-intensity immunosuppression, which has its own serious side effects.”

While transplantation of pancreatic islets has been investigated for several decades as a treatment and potential cure for type 1 diabetes, its success has been limited. Along with the risk of rejection that accompanies all organ transplants – a risk that is even greater for cross-species transplants – donated islets are subject to the same autoimmune damage that produced diabetes in the first place. The immunosuppressive drugs used to prevent organ rejection significantly increase the risk of infections and some cancers, and they also can contribute directly to damaging the islets. Among the strategies investigated to protect transplanted islets are enclosing them in gel capsules and manipulating the immune environment around the implant. The MGH-developed approach includes aspects of both approaches.

Previous research from the MGH team demonstrated that elevated expression of a chemokine – a protein that induces the movement of other cells – called CXCL12 repels the effector T cells responsible for the rejection of foreign tissue while attracting and retaining regulatory T cells that suppress the immune response. For the current study they investigated how either coating islets with CXCL12 or enclosing them in CXCL12 gel capsules would protect islets transplanted into several different mouse models.

Their experiments revealed that islets from nondiabetic mice, either coated with CXCL12 or encapsulated in a CXCL12-containing gel, survived and restored long-term blood sugar control after transplantation into mice with diabetes that was either genetically determined or experimentally induced. CXCL12-encapsulated islets were even protected against rejection by recipient animals previously exposed to tissue genetically identical to that of the donor, which usually would sensitize the immune system against donor tissue. CXCL12-encapsulated pig islets successfully restored blood sugar control in diabetic mice without being rejected. The ability of CXCL12 – either as a coating or encapsulating gel – to repel effector T cells and attract regulatory T cells was also confirmed.

“While studying this procedure in larger animals is an essential next step, which is currently underway with the support of the Juvenile Diabetes Research Foundation, we expect that this relatively simple procedure could be readily translatable into clinical practice when combined with technologies such as stem-cell-derived islets or other insulin-producing cells and advanced encapsulation devices,” says Poznansky, an associate professor of Medicine at Harvard Medical School. “We also hope that CXCL12 will have a role in protecting other transplanted organs, tissues and cells as well as implantable devices, a possibility we are actively investigating.”

http://www.medicalnewstoday.com/releases/289590.php?tw

 

Learn More +

Unlimited access to all the essential project updates latest diabetes research news, and more.