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Bioengineering of an Intraabdominal Endocrine Pancreas

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Bioengineering of an Intraabdominal Endocrine Pancreas

US scientists have demonstrated a method of achieving insulin independence within type 1 diabetes.

A 43-year-old single mother with dangerously difficult-to-control diabetes had insulin-producing islet cells transplanted into her omentum* - a fatty membrane in the belly.

The cells began producing insulin faster than expected, and after one year she is doing well and doesn't need insulin injections, researchers from the Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine said.

"We're exploring a way to optimize islet cell therapy to a larger population. This study gives us hope for a different transplant approach," said the study's lead author, Dr. David Baidal. He is an assistant professor at the DRI.

Currently, islet cells from deceased donors are transplanted into the liver, but that's not an ideal option.

When the liver is used for islet cell transplants, only a limited amount of islet cells can be transplanted. There's also a risk of bleeding when the transplant is done and the possibility of other complications, the researchers said.

Also, with islet cell transplants in the liver, the underlying autoimmune condition is still there. And, if people didn't take immune-suppressing medication, the new islet cells would likely be destroyed.

The woman in the study had a 25-year history of type 1 diabetes. She also had severe hypoglycemia unawareness.

"Her quality of life was severely impacted. She had to move in with her parents. And, if she traveled, she had to travel with her father" in case her blood sugar levels dropped dangerously low, Baidal explained.

The surgery was minimally invasive, and the islet cells were placed on a "scaffold" that eventually dissolved. There were no complications, the researchers said.

"We were happily surprised when her glucose [blood sugar] profile improved quite dramatically," Baidal said.

This new research was a proof-of-concept study expected to be the first step on a path toward developing a mini-organ called the BioHub.

DRI BioHub would be a biological platform made by a combination of donor islets with a patient's own blood plasma. When a molecule called thrombin is added to the mixture, a gel-material is created that sticks to the omentum and holds the islets in place. Over time, the body absorbs the gel and leaves the islets intact.

In its final stages, the BioHub would mimic a pancreas and act as a home for transplanted islet cells, providing them with oxygen until they could establish their own blood supply.

Baidal said the study results need to be replicated in other patients, and the researchers want to see what happens post-treatment over a longer time. The researchers plan to test the omentum as a site in five more patients.

From the research paper:

  • A total of 602,395 islet equivalents from one deceased donor were combined with autologous plasma and laparoscopically layered onto the omentum.
  • Recombinant thrombin (Recothrom) was layered over the islets, followed by another layer of autologous plasma to generate a degradable biologic scaffold.
  • Insulin was discontinued 17 days after the transplantation. 

"In this patient, islet transplantation onto the omentum restored euglycemia and insulin independence. A functional decline was observed at 12 months with an increase in insulin sensitivity, which we speculate may have been due to the switch from tacrolimus to sirolimus. The patient continued to have stable glycemic control without exogenous insulin and without episodes of hypoglycemia."

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