Baylor Dallas team’s remarkable discovery of regeneration of islet cells from leftover tissue could lead to efficiencies in transplantation and improved patient quality of life

Baylor University Medical Center at Dallas (Baylor Dallas), part of Baylor Scott & White Health, operates the only transplant program in Texas offering total pancreatectomy followed by islet auto-transplantation (TPIAT) for acute relapsing and chronic pancreatitis. There are few programs with as much experience in this complex procedure. Since it began in 2006, Baylor Dallas has performed more than 250 procedures, making it one of the top programs in the country.

For patients with severe chronic pancreatitis, surgical removal of the pancreas is often necessary to relieve intense pain. However, this procedure results in diabetes, leaving patients dependent on exogenous insulin. Islet cell auto-transplantation can reduce or even eliminate the need for insulin. A TPIAT is performed to alleviate the pain of chronic pancreatitis and retain the endocrine function.

The need for insulin varies among patients who undergo an islet cell transplant. About one-third of patients do not need insulin; One third need small amounts of insulin and a third are completely insulin dependent.

“This is just one piece of the puzzle,” said Sebastian Danobeitia, MD, PhD, abdominal transplant surgeon on the medical staff at Baylor Dallas. “We are looking at different ways to improve outcomes to make islet cell transplantation more durable and accessible to patients.”

Protecting the islets from inflammatory injury

Islet cell transplantation using isolated and purified human allogenic islet cells has been shown to offer a potential “cure” for type 1 diabetes. However, the procedure has been limited by a significant loss of transplanted islets, partly due to the innate immune response, leading to poor long-term function.

A $750,000 grant from Breakthrough T1D, a leading global type 1 diabetes research and advocacy organization, was recently awarded to Bashoo Naziruddin, PhD, researcher at Baylor Scott & White Research Institute-the research arm of Baylor Scott & White Health-and Director of Islet Cell Processing Lab at Baylor Dallas, to study ways to suppress the immune response during islet cell transplantation procedures.

The research is based on animal models but will soon move forward to clinical trials, said Dr. Naziruddin.

“Our results using lab experiments have been very promising and we are ready to take it to the clinical side,” he said.

During the process of extracting the islet cells from the pancreas and infusing them in the liver, numerous cells are often lost due to this innate immune response, Dr. Danobeitia explained.

When purified allogeneic islets are infused, it invokes an acute inflammatory response that destroys 25-75% of islet mass within days leading to poor engraftment.

But the efficacy of islet transplants can be improved by minimizing islet cell loss using TAK-242, a clinically validated small molecule inhibitor of the toll-like receptor system, he said.

“We propose to evaluate efficacy of the TLR4 selective inhibitor TAK-242 to suppress innate and potentially adaptive immune responses to islet transplants,” Dr. Danobeitia said.

When isolated islet cells from the pancreas are injected into the liver, the overwhelming inflammatory response often damages these cells, reducing the number of viable islets needed for optimal function, Dr. Danobeitia, said. But if the inflammation is controlled, it would be possible to protect more islet cells, potentially allowing patients to achieve longer insulin-free periods.

“Sometimes 75 percent of the cells are removed, other times it is only 5 to 10 percent,” he said. “Those who receive lower volumes of cells might go two months to a year without needing insulin, but those who receive larger volumes of cells could go years to decades.”

This research holds the potential to greatly improve the lives of individuals with type 1 diabetes, as well as those with chronic pancreatitis undergoing total pancreatectomy and islet auto-transplantation.

Minimizing the need for lifelong insulin could not only enhance patients' quality of life but also lower their risk of complications like heart and kidney disease. Additionally, this would have a positive impact on healthcare costs.

The long-term goal of this project is to initiate Phase I/II clinical trials of allogenic islet transplants into T1D patients using TAK-242 to suppress innate immune response and improve long term islet graft function.

Using lost tissue

The Baylor Dallas transplant team is working on a novel method to make the auto-transplantation even more efficient through the identification of human islet progenitor cells (IPCs) that can be differentiated into glucose-stimulated insulin and glucagon-secreting cells. Simply stated, the goal would be to use tissue that is overlooked, and give it back to the patient. Ultimately, this could significantly reduce the number of deceased donor pancreases and islet tissue required for clinical islet cell transplantation. The team presented their initial findings in a plenary session at the American Transplant Congress in June 2024.

During islet cell isolation and transplantation, fractions of tissue that surround the cells are normally discarded. Dr. Naziruddin’s team has discovered stem cells within the leftover tissue that can potentially guide the regeneration of islet cells,” explained Dr. Danobeitia. “This finding holds tremendous potential. Imagine if we could isolate these cells, specifically target and treat them, encouraging them to expand and grow in clusters that closely resemble functional islet cells”.

This discovery is transformative not only for autotransplantation but also for allotransplantation of islets. In auto-transplantation, reusing a patient’s own pancreatic tissue to regenerate functional endocrine cells could enable long-term insulin independence without the risk of immune rejection. For allotransplantation, this approach could reduce reliance on donor organs and islet tissue, potentially increasing availability for patients who rely on donor organs from deceased donors. By preserving donor resources and improving cell survival and function, this method has the potential to enhance outcomes and expand access to islet cell transplantation across both patient groups. Dr. Danobeitia said.