Baylor Scott & White researchers identify a novel site for islet cell transplantation

Patients experiencing the intractable pain of chronic pancreatitis may be candidates for total pancreatectomy followed by autologous islet cell transplantation (TPIAT). This innovative procedure has been documented to be very effective in controlling pain and restoring insulin secretion in a large number of patients. Baylor University Medical Center, (Baylor Dallas) part of Baylor Scott & White Health, has performed more than 200 successful islet cell transplants, placing it among the top five centers in the United States based on total case volume of this procedure.

Infusion of islets into the portal vein is the standard method in islet transplantation. However, a major drawback of this approach is the limited islet tissue volume that can be transplanted. As loading tissue volume increases, portal venous pressure also increases. As a result, the procedure carries the risk of portal venous embolic occlusion, hemorrhage and thrombosis. However, studies have shown that the more islets that are transplanted the better the outcomes.

To address this major limitation, the research team in the Islet Cell Laboratory at Baylor Dallas looked at other options. The peritoneal cavity, which has a large capacity for grafting tissue volume, was explored as a secondary site following portal infusion

“We found the peritoneal cavity was not efficient in maintaining islet function,” says Bashoo Naziruddin, PhD, director of the Islet Cell Laboratory at Baylor Dallas. “Our team then developed the novel idea of transplanting islets into the preperitoneal space. This space has the capacity for large tissue volume and the capacity for revascularization, which is essential to the survival of the transplanted islets.”

The approach was designed to use anatomical features of the peritoneum with potential for replication at multiple sites of a recipient to increase islet tissue volume. To test this hypothesis, the islet cell research performed several separate experiments. Results were published in the November 2020 issue of the journal Transplantation.

First, the team transplanted syngeneic mouse islets into the preperitoneal space. They found this approach performed better than the peritoneal cavity and that islet function was supported for 60 days with no issues. Next, the team transplanted human islet cells into the preperitoneal space of the mice and found them to be functioning very well long term.

The research team used advanced technology with biomarkers to look at islet function and possible damage. A previous study from the Baylor Scott & White laboratory showed that microRNA-375 is a reliable marker of islet damage after transplantation. Results indicated that the preperitoneal space reduces damage to the transplanted islets. FDG-PET/CT imaging was performed to observe the viable islets 100 days after transplant, which were found to be functionally intact.

Since the study was published, more than 10 patients have undergone islet cell transplant at Baylor Dallas with partial islet infusion into the preperitoneal space. No adverse events have been observed, and the islets were well tolerated.

“This is a very exciting development. Our research team has solved a long-standing problem faced by the surgical team with autologous islet transplant,” says Ernest Beecherl, MD, FACS, director of islet autotransplantation at Baylor Dallas. “During the isolation process, we always have excess islets that we used to discard because there is only so much tissue you can put in the portal vein before there is a risk of thrombosis. Now we have a backup location to place the excess islets instead of discarding them, which should lead to better outcomes for our patients.”

Baylor Dallas is the only transplant program in Texas offering TPIAT for acute relapsing and chronic pancreatitis.