Islet-Cell Transplants: 3 Tech Solutions May Soon End the Need for Shots and Pumps

Scientists are looking to stem cells, special pouches and surprising transplant sites (including the eyes and the abdomen) to bring this promising diabetes solution closer to reality

Tech Solutions May Enable a Future with Islet Cell TransplantsIslet-cell transplants of the future could include genetically-altered islets from pigs.

Thanks to advances in transplant medicine, you can receive a new heart…or liver…or lung…or kidney. Researchers hope to add insulin-making islet cells to that list soon—and help people with type 1 and type 2 diabetes who now rely on insulin shots and insulin pumps to break free and live easier, healthier lives.

Currently, people with diabetes can receive a whole-pancreas transplant. But these procedures are rare. And because they require a lifetime of immune-suppressing drugs to prevent transplant rejection, are usually given only to those already receiving a kidney transplant. Researchers are moving ahead with transplanting just the islet cells. In studies in people with type 1 diabetes, this experimental procedure reduces the need for insulin shots and cuts the risk for unpredictable, life-threatening low blood sugar episodes.

But the islets may only live for a few years. Many die during transplantation, too. Recipients must take lifelong anti-rejection drugs. And donor cells, which come from deceased human organ donors, are in short supply. Here’s the latest on the solutions scientists in the US and around the world are exploring.

Problem: Scarce Donor Cells 
Future Solution: Stem Cells

Islets come from the pancreas of a deceased organ donor. But fewer and fewer donors have a pancreas healthy enough to use for extracting islet cells, according to transplant expert Jon S. Odorico, MD, professor of surgery at University of Wisconsin-Madison School of Medicine and Public Health.  “Just 11-12% can be used for whole-pancreas transplants and slightly more for islet cells,” says Dr. Odorico, chairman of the Pancreas Transplant Committee of the United Network for Organ Sharing, which coordinates organ transplants in the US. “Twenty years ago, we could use 30-50%. But the population as a whole is becoming more overweight and obese and more people have diagnosed or undiagnosed diabetes.”

If and when the FDA approves islet-cell transplants for widespread use, a bigger supply will be needed to meet growing demand. “Alternative sources of pancreatic beta cells promise to make β-cell replacement therapy available to a much broader number of patients,” islet transplant researchers Christian Schuetz and James F. Markmann of Massachusetts General Hospital note in a 2016 article in the journal Current Transplantation Reports. 

Two fascinating and very different alternatives scientists have looked at in recent years include genetically-altered islets from pigs and implanting young human islets that would develop and multiply after a transplant. One solution that’s making headlines and moving forward quickly in research: Using stem cells to create new islets. In California, San Diego-based ViaCyte Therapeutics recently launched a second human study in January 2018 that’s implanting islets developed in a process that begins with stem cells.  

The safety of the implants and their ability to produce insulin in response to changing blood-sugar levels will be tracked in about 40 adults with “brittle” diabetes. The islets are encased in a specialized pouch about half the size of a business card; these devices, called PEC-Direct, are implanted under the skin on volunteers’ arms and elsewhere.

“After implantation, the cells are expected to mature into the full complement of islet cells, including insulin-producing beta cells, offering a potential functional cure for patients with high-risk type 1 diabetes,” according to ViaCyte. “Besides being a potentially important advance for the patients with the greatest needs, PEC-Direct is also considered a stepping stone to cell therapy for all insulin-requiring patients.”

Meanwhile, Cambridge Massachusetts-based Semma Therapeutics is also developing beta cells that can monitor blood sugar levels and release insulin as needed. Launched by Harvard University professor Douglas Melton, PhD, co-chair of the Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, the company is named for his children Sam and Emma, both of whom have type 1 diabetes according to MIT Technology Review.

Over more than a decade, Melton’s lab developed a process that uses stem cells to generate “billions of functional, insulin-producing beta cells which have the potential to control blood sugar in people living with diabetes,” according to the company. In December 2017, Semma announced it had raised $114 million to finance new studies of its stem cell-derived beta cells—including human studies in the future, according to Mark C. Fishman, MD, chairman of the board at Semma Therapeutics.

Problem: Your Immune System Wants to Destroy Transplanted Islet Cells
Future Solution: Protective Pouches 

Right now, people who receive islet-cell transplants must take immune-suppressing drugs for life so that their body doesn’t reject and kill the cells. The reason: Like any transplanted organ or body part, transplanted islet cells are “foreign” objects that your immune system sees as intruders. But immune suppressants can be risky, raising odds for everything from infections to bacterial and viral infections as well as for mouth sores, nausea, diarrhea, high cholesterol, high blood pressure, fatigue and even some cancers.

One possible solution: Putting the islets in special pouches so that the immune system doesn’t know they’re there. Researchers across the US are experimenting with a wide variety of protective containers. “One of several approaches under investigation with National Institute of Diabetes and Digestive and Kidney Disease support is immuno-isolation—physically separating the islets from the recipient’s immune system,” says Thomas L. Eggerman, MD, PhD, program director of the Division of Diabetes, Endocrinology, and Metabolic Diseases at the National Institute of Diabetes and Digestive and Kidney Diseases. “Researchers are identifying biocompatible materials that can be used to create a chamber that allows oxygen and nutrients to reach the islets while protecting them from attack by the immune system. Ideally, this chamber could be easily implanted and removed from the body."

Scientists from the Massachusetts Institute of Technology (MIT), Boston Children's Hospital, and several other institutions recently reported on a new pouch material derived from brown algae. In lab studies, islets in the little envelopes survived for at least six months. The pouches let in oxygen and other nutrients to keep the islets alive. And the islets were able to sense blood-sugar levels and release insulin as needed. 

A system made from polycaprolactone, a medical-grade polyester also used in night-time mouth guards and surgical sutures, is in research at the San Francisco-based biotech start-up Encellin. “Our proprietary technology will be loaded with glucose-responsive insulin-secreting cells, and implanted under the skin,” notes Encellin founder and CEO Crystal Nyitray on the company’s website. “Once inside the device cells will be protected from the immune system but still able to maintain nutrient exchange to respond to their environment.”

Problem: Lots of Islets Die in a Conventional Cell Transplant
Future Solution: Put Islets Somewhere Else

Most transplants put islets in the liver–but many recipients need repeat transfusions. “The standard procedure infuses donor islet cells into the portal vein, where they travel to the liver and become embedded in small blood vessels,” explains Camillo Ricordi , MD, director of the DRI and the Stacy Joy Goodman Professor of Surgery, distinguished professor of medicine, professor of biomedical engineering, microbiology and immunology at the University of Miami Miller School of Medicine. “It is a simple procedure, but contact with the bloodstream triggers an inflammatory reaction that can destroy 50% or more of the islet cells.” 

So scientists are looking at other places in the body to house transplanted islets. One technique developed at the DRI, transplants islet cells to a recipient’s omentum—the curtain of fat at the front of the abdomen—along with a protective gel made in part from the recipient’s own blood plasma. Meanwhile, human studies are planned or underway that transplant islets to the skin under the arms, the back of the eyes and the inner wall of the stomach or small intestines.

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