There are two things driving Jessica Weaver’s continuing interest in islet transplantation and type 1 diabetes.
“There’s already a treatment – insulin injections – but it’s not a cure, and in the long term, patients can still have secondary complications that can impact the quality of their lives,” says Weaver, a postdoc in the lab of Andrés García at the Petit Institute for Bioengineering and Bioscience. “So, one reason for researching islet transplantation is to try and develop a long-term cure for people with type 1 diabetes.”
The other reason hits a bit closer to home. Her husband, Atlanta attorney Oren Snir, has type 1 diabetes. So when it comes to her work, “he is the lens that I look through,” says Weaver, whose clear-eyed focus on a disease that affects about 1.25 million Americans is bringing her some well-earned recognition.
Recently, Weaver was awarded an JDRF (formerly known as the Juvenile Diabetes Research Foundation) Postdoctoral Fellowship. The award supports Weaver’s full-time research over three years, providing for the transition from postdoctoral fellow to, ideally, an independent, faculty-level post.
“This is a very competitive award, and Jessica is a perfect fit for it,” says García, the Rae and Frank H. Neely Chair in Mechanical Engineering and Regents’ Professor of Mechanical Engineering (and also director of the interdisciplinary Bioengineering Graduate Program). “She truly is dedicated to developing engineering solutions for the treatment of type 1 diabetes.”
Additionally, Weaver was selected as the Young Investigator Award winner for the upcoming Regenerative Medicine Workshop at Hilton Head (March 1-4), where her research presentation will highlight a different aspect of her research, while still keeping the focus tight on type 1 diabetes, formerly known as juvenile diabetes.
“When you have a loved one that you want to help, you think in terms of translatability. You want to develop something that works really, really well, because the stakes are high.”
Each year, about 40,000 people in the United States, mostly children and young adults, are diagnosed with type 1 diabetes. The disease is characterized by the body’s inability to produce insulin, a hormone used to get glucose from the bloodstream into the cells of the body.
Islets are clusters of cells in the pancreas that make insulin. In islet transplantation, cells are taken from a donor pancreas and delivered to a diabetic recipient, where the implanted islets make and release insulin, ending the need for daily insulin injections, effectively ending the disease.
That’s the hope anyway. There are some issues.
“We’ve proven the feasibility over the last 20 years that you can transplant insulin-secreting cells into patients,” Weaver says. “But one of the challenges is, they don’t last very long. And if you’re using a donated organ to deliver cells to a patient, you want it to last, to work long term.”
The bioengineers in García’s lab are using biomaterials-based strategies to improve the long-term survival of these islet grafts. The key is protecting the transplanted cells from the body’s immune system, so part of Weaver’s JDRF-sponsored research involves trying to eliminate the need for immunosuppressants.
Keeping these precious islet cells from a donor organ alive depends on a number of factors. One that Weaver is exploring in detail for her Junior Investigator research presentation involves investigating ideal transplantation sites.
“This technique has been around for about 20 years, and the site they use for transplant has been the portal vein of the liver. That location has demonstrated the feasibility of restoring normal blood glucose,” Weaver says.
Unfortunately, it’s also a hostile transplant site, like trying to storm a fortified beachhead, with predictable results. Islets delivered through the portal vein survive a median of 35 months, according to Weaver.
“A main factor is that around 60 percent of the islets are immediately killed,” she says. “They go into the blood stream and are entrapped in the narrowing vasculature of the liver. Shoved into these tiny blood vessels, they experience stresses they don’t receive in their native environment.”
Using García’s hydrogel platform, Weaver and colleagues can explore multiple transplantation sites, simultaneously. It’s critical to find the optimum site because currently, using the liver portal vein comes with a very high cost.
The islet cells used in this procedure come from a donated human pancreas, “and what happens when using the liver site is, sometimes it takes two to four pancreata to restore normal blood glucose,” says Weaver, who has been on this track for nine years – as an undergraduate researcher and then as a grad student at the University of Miami.
“Our goal is to get it down to a single pancreas donation per single recipient,” she says. “We want to make sure we can get the most cells from that one organ into the patient and ensure their survival.”
It sounds simple, but she knows how complicated it is. Nine years of research, among other things, have taught her that. And she understood early on how dear are the natural tools she is trying to harness for the good of millions, or the good of one in particular. This became clear one day when she was still an undergrad back in Florida, shortly after she and her future husband started dating.
“We received a donation of some human islet cells to study, from a pancreas that couldn’t be transplanted for one reason or another,” she recalls. “I remember holding those cells, those precious human cells in my hand and thinking to myself, ‘this is all he needs. If only I could take these home give them to him.’”
That may be when the research moved beyond the abstract, becoming abundantly practical, because every time she cures an animal subject in one of her studies the work becomes a little more profound, a little more urgent.
“When you have a loved one that you want to help, you think in terms of translatability,” Weaver says. “You want to arm the clinical community with the best possible options. You want to develop something that works really, really well, because the stakes are high.”