GEORGIA TECH / EMORY (US) — Scientists reversed Type 1 diabetes in mice in as little as 10 days using a new technique to transplant cells.
The research team engineered a biomaterial to protect the cluster of insulin-producing cells—donor pancreatic islets—during injection. The material also contains proteins to foster blood vessel formation that allow the cells to successfully graft, survive and function within the body.
“It’s very promising,” says Andrés Garcia, professor of mechanical engineering at the Georgia Institute of Technology. “There is a lot of excitement because not only can we get the islets to survive and function, but we can also cure diabetes with fewer islets than are normally needed.”
Andrés Garcia, Georgia Tech professor of mechanical engineering, and Emory researchers have successfully engrafted insulin-producing cells into a diabetic mouse model, reversing diabetic symptoms in the animal in as little as 10 days. (Credit: Georgia Tech)
This type of transplant therapy, although promising, has shown limited long-term success. While control of glucose levels is often improved, most patients revert to using some insulin to manage diabetes symptoms.
Unsuccessful transplants can be attributed to several factors, researchers say. The current technique of injecting islets directly into the blood vessels in the liver causes approximately half of the cells to die due to exposure to blood clotting reactions.
Also, the islets—metabolically active cells that require significant blood flow—have problems hooking up to blood vessels once in the body and die off over time.
Add the hydrogel
Georgia Tech and Emory University researchers engineered a hydrogel, a material compatible with biological tissues that is a promising therapeutic delivery vehicle. This water-swollen, cross-linked polymer surrounds the insulin-producing cells and protects them during injection.
The hydrogel containing the islets was delivered to a new injection site on the outside of the small intestine, thus avoiding direct injection into the blood stream.
Once in the body, the hydrogel degrades in a controlled fashion to release a growth factor protein that promotes blood vessel formation and connection of the transplanted islets to these new vessels. In the study, the blood vessels effectively grew into the biomaterial and successfully connected to the insulin-producing cells.
Four weeks after the transplantation, diabetic mice treated with the hydrogel had normal glucose levels, and the delivered islets were alive and vascularized to the same extent as islets in a healthy mouse pancreas.
The technique also required fewer islets than previous transplantation attempts, which may allow doctors to treat more patients with limited donor samples. Currently, donor cells from two to three cadavers are needed for one patient.
Will it work in people?
While the new biomaterial and injection technique is promising, the study used genetically identical mice and therefore did not address immune rejection issues common to human applications. The research team plans to study whether an immune barrier they created will allow the cells to be accepted in genetically different mice models. If successful, the trials could move to larger animals.
“We broke up our strategy into two steps,” says Garcia, a member of Georgia Tech’s Petit Institute for Bioengineering and Bioscience. “We have shown that when delivered in the material we engineered, the islets will survive and graft. Now we must address immune acceptance issues.”
The Regenerative Engineering and Medicine Center at Georgia Tech and Emory, the Atlanta Clinical and Translation Science Institute, the Center for Pediatric Healthcare Technology Innovation at Georgia Tech, the Department of Veterans Affairs Merit Review Program, the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases, and JDRF funded the research.
The findings will be published in the June issue of the journal Biomaterials.
Source: Georgia Tech