Islet transplants from fish?

The shortage of human organ donors has led scientists to investigate animals as a potential source for transplantable organs or tissues. Pigs are often mentioned because of their size: similar to ours.

Recently, prospects for xenotransplantation brightened when Harvard geneticist George Church demonstrated the removal of dozens of endogenous retroviruses from the pig genome, in a tour de force of the CRISPR/Cas9 gene editing technique.

Emory researchers Susan Safley and Collin Weber have been exploring the possibility of using different animals for xenotransplantation: fish, specifically tilapia.

Why fish? This review details several advantages tilapia may offer in the field of islet transplant, but first – a reminder about islets.

Islets are the clusters of cells in the pancreas that produce insulin. Several clinical trials, including this one led by Emory’s Nicole Turgeon, have shown that islets isolated from deceased human donors can restore normal blood sugar regulation in patients with type 1 diabetes. Still, obstacles remain such as the shortage of human islets, and the loss of insulin independence over time, even with the use of drugs that hold off immune rejection.

For islet transplant, here are some of the proposed advantages presented by tilapia:

*tilapia have large, distinct islet organs called Brockmann bodies that are easy to isolate

*tilapia grow quickly and cost less to raise than pigs

*tilapia islets are resistant to hypoxia, thought to contribute to graft loss

*tilapia do not express alpha (1,3) gal, a carbohydrate structure present on mammalian cells that causes hyperacute rejection [although, this issue has been addressed in genetically modified pigs]

Safley and Weber’s work, published in the journal Xenotransplantation in 2014, has shown that encapsulated tilapia islets can maintain normal blood sugar regulation in diabetic mice. The fish islets last several months when the mice are given immunosuppressive drugs.

The capsules are made of the same stuff, alginate, used by cardiologists Rebecca Levit and W. Robert Taylor to package mesenchymal stem cells for the treatment of cardiovascular diseases. Indeed, Levit and Taylor have credited Weber’s team for optimizing alginate encapsulation for cell therapy.

In their paper, Safley and Weber note that the alginate capsules they used permit host antibodies to access the islet cells, promoting immune rejection. In contrast, the alginate capsules described in the cardiovascular papers exclude antibodies, possibly because of their size or chemical coating, yet still allow the passage of smaller proteins such as insulin. Having islet capsules that bar antibodies could facilitate islet cell survival, the authors conclude.

In addition, Safley reports she and Weber have been planning a collaboration with Canadian researchers who have developed transgenic fish producing human insulin, which could overcome another immune-related barrier.

 

 

 

 

 

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Posted on by Quinn Eastman in Immunology Leave a comment

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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