Encapsulating Insulin-Producing Cells For Possible Diabetes Therapy

November 05, 1998

DURHAM, N.C. -- Duke University chemists led by assistant professor Mark Grinstaff are developing novel liquid polymers that can be solidified by a quick flash of laser light to seal transplanted insulin-producing cells inside a selectively permeable capsule, thus preventing rejection by diabetics' immune systems.

An interdisciplinary collaboration, involving Duke's department of chemistry as well as its medical center and School of Engineering, has already reduced the excessive blood sugar levels of experimental diabetic rats for as long as eight days after transplanting such insulin-secreting microcapsules into those animals' bodies.

Grinstaff's group prepared their report for presentation Thursday during the American Chemical Society's 50th southeastern regional meeting. The research is funded by Research To Prevent Blindness, Inc., The North Carolina Biotechnology Center, the Whitaker Foundation and the National Institutes of Health.

Each microcapsule encloses an individually-transplanted cell tissue cluster called an islet of Langerhans. Normally residing in the pancreas, these islets are "little endocrine organs" that "make insulin and multiple hormones in addition to insulin," said Diane Hatchell, a Duke professor of ophthalmology and cell biology who adds her medical expertise to the collaboration.

"The trick is to see if we can design a system in which we can transplant the islets from one species into another species by using our microcapsule," Grinstaff said.

Diabetes, the third leading cause of death in the United States, involves disruptions to normal pancreatic production of insulin, which serves to regulate glucose levels in the bloodstream.

Medical researchers have explored the transplantation into diabetics of healthy Islets of Langerhans, perhaps from the pancreases of pigs, as one possible diabetes therapy. But the immune system would normally identify such transplanted islets as "foreign," and thus target them for destruction.

The microcapsules being developed in Grinstaff's lab would avoid this dilemma by not allowing large molecules such as immunoglobin G (IgG) antibodies, a key part of the immune system's defenses against foreign invaders, to enter the microcapsule. The microcapsules wrap each islet in a semipermeable mesh.

"IgG has a molecular weight of about 150,000, and insulin's is about 6,000," Grinstaff said. "That's a very big difference. So the idea is that we build a filter that can keep antibodies from entering but which is permeable to small molecular weight materials like insulin or glucose or oxygen or other nutrients."

The islet-enclosing microcapsules are made of hyrogels, a class of long-chain polymer molecules that possesses a high water content. In this case, the polymer chains are links of simple sugars and are thus known as polysaccharides.

The polysaccharide used in the experiments, hyaluronic acid, is a natural component of the lubricating fluid in human joints as well as the vitreous gel that fills the eye. It is therefore "well-known by the body's immune system," Grinstaff noted.

During the last 1? years, Grinstaff, postdoctoral researcher Anne Pfister-Serres and graduate student Kim Smeds have developed techniques using laser light to "photo cross-link" viscous liquid hyaluronic acid so that its molecular chains mesh together into solid gels.

Meanwhile, Hatchell faces her own set of medical challenges in extracting the islet cells for transplantation. "We have to use a very harsh enzyme called collagenase to dissolve the connective tissue of the pancreas and get out these little clusters that contain 1,000 or so cells, without damaging them," she said.

One problem is that removing islets separates them from the blood supply that normally keeps them healthy, Hatchell added. "We don't understand how much injury we do to the islets during this isolation procedure. It's been difficult to even show that the free islets are functional immediately after isolation."

Despite those obstacles, Duke researchers have already done their first preliminary trials in animals, harvesting islets from dogs, surrounding them with polymer, and transplanting the encapsulated islets into the inter-peritoneal cavity of diabetic rats. In their best results so far, high blood sugar levels were reduced for eight days in one rat, but have not dropped to normal.

"We have been able to do a transplant and see a reduction in blood glucose, and that was very encouraging," Grinstaff said. "It leaves a lot more questions for us to go after, and a lot more work for us to do."

If islet transplantation ever becomes a reality, Hatchell said pigs would likely be the "donors of choice." That's because "porcine insulin is what diabetics took for years until there was recombinant human insulin," she added. "We know the human body can tolerate it."

Grinstaff's chemistry team also has been studying how well different sized meshes of crosslinked polymer block entry of IgG antibodies while allowing insulin and other nutrients to successfully diffuse. For some of these evaluations, the researchers have worked with David Katz, a professor of biomedical engineering whose laboratory has extensive experience in measuring diffusion properties of hydrogel materials.
-end-
Note to editors: Two presentations on different aspects of this research will be delivered at 1:20 and 1:40 p.m.Thursday, Nov. 5, 1998, in the Crown B meeting room of the Sheraton Imperial Center in Research Triangle Park, N.C. during the American Chemical Society's Southeastern Regional Meeting.

Duke University

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System 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.