13 May 2013

Beta cells in a package

A biodegradable hydrogel has been developed for the treatment of type 1 diabetes

LifeSciencesToday based on Georgia Tech: Biomaterial Shows Promise for Type 1 Diabetes TreatmentThe creation of engineered biomaterials for cell transplantation is a promising direction in the development of potential treatments for type 1 diabetes, which affects about 3 million people in the United States alone.

Engineers at the Georgia Institute of Technology (Georgia Tech) and doctors at Emory University successfully transplanted insulin-producing cells into mice with a model of diabetes, reversing the symptoms of the disease in just 10 days.

They developed a biomaterial to protect a cluster of insulin-producing cells – donor pancreatic islets – during their introduction into the body. In addition, the new material contains proteins that accelerate the formation of blood vessels, which allows cells to successfully take root, grow and function in the body.


An image of a transplanted mouse with an islet diabetes model delivered in a hydrogel.
The red areas are insulin-producing cells, the green ones are blood vessels, and the blue ones are DNA in cell nuclei.
Photo: Georgia Tech"This is a very promising result," said Andres Garcia, professor of mechanical engineering at Georgia Tech.

"It gives us the opportunity not only to ensure the survival and functioning of the islets, but also to treat diabetes using a smaller number of them than usual."

The study, conducted by Professor Garcia in partnership with Dr. Robert Taylor and Peter Thule from Emory University, is published online in the journal Biomaterials (Vascular bio-synthetic hydrogel for enhancement of pancreatic islet engraftment and function in type 1 diabetes).

Type 1 diabetes is a chronic disease caused by insufficient production of the hormone insulin by the pancreas, which transports sugars and other nutrients to the tissues, where they are converted into energy necessary for daily life.

Most patients with type 1 diabetes currently maintain their blood glucose levels with a few daily injections of insulin or an insulin pump. But insulin therapy has its limitations. To be effective, it requires careful measurement of blood glucose levels, accurate dose calculations and regularity of drug administration.

Pancreatic islet transplantation was revived as a promising method of type 1 diabetes therapy in the late 1990s. Patients with this disease usually find it difficult to follow a strict regime – several daily injections of insulin, which, in terms of long-term treatment results, only partially improve their condition. Successful islet transplantation would eliminate the need for insulin administration. However, although clinical trials of islet transplantation had some success (glucose control often improved), in most patients the symptoms of the disease returned, forcing them to resort to injections of some amount of insulin again.

The failures of such transplants may be due to several factors. In particular, today's technology of injecting islets directly into the blood vessels of the liver is the cause of the death of about half of the cells as a result of reactions that ensure blood clotting. In addition, once in the body, islets – metabolically active cells that require significant blood flow – face the problem of "connecting" to blood vessels and die over time.

Researchers have designed a hydrogel compatible with biological tissues, which is a promising therapeutic delivery vehicle. This water-swollen cross-linked polymer surrounds the insulin-producing cells and protects them during administration. The hydrogel containing islets is injected not into the vessels of the liver, but into the outer surface of the small intestine, which avoids injection directly into the bloodstream.

Once in the body, the hydrogel decomposes in a controlled manner, releasing a protein growth factor that stimulates the formation of blood vessels and their integration into the transplanted islets. In the experiments carried out, blood vessels effectively germinated into biomaterial and successfully "connected" to insulin-producing cells.

Four weeks after transplantation, normal glucose levels were observed in mice with a diabetes model, and the delivered islets were alive and vascularized to the same extent as the pancreatic islets of healthy mice. In addition, compared to earlier transplantation technologies, the new method requires fewer islets, which in conditions of shortage of donor material allows doctors to help more patients. Currently, cells obtained from two or three corpses are required for transplantation to one patient.

Although the new biomaterial and the method of administration are very promising, it should be emphasized that genetically identical mice were used in the experiments. This means that scientists have not encountered the problem of immune rejection, usually observed in clinical transplants. However, they have already received funding to study whether cells protected by the immune barrier they have created will be accepted by the body of genetically different mouse models. If successful, it is planned to continue experiments on larger animals.

"We have broken our strategy into two stages," says Garcia, a researcher at the Petit Institute for Bioengineering and Bioscience at Georgia Tech. "We have shown that when delivered in the material designed by us, the islands survive and take root. Now we have to address the problems of immune engraftment."

Portal "Eternal youth" http://vechnayamolodost.ru13.05.2013

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