By Avigayil Kadesh
Successful pancreatic islet transplants from mammals, such as pigs, to patients with type 1 diabetes may be possible, according to an Israeli study published in the journal
PLoS ONE.
Islets are where the pancreas produces the hormone insulin. Type 1 diabetes (formerly called juvenile diabetes) results from a problem with the production of insulin, which carries glucose to the body’s cells. Transplants of healthy human islets from cadavers have been successful in allowing recipients to stop using injected insulin on a daily basis.
But there aren’t nearly enough human donors, considering that in the United States alone, 40 new cases of Type 1 diabetes are diagnosed each day (adding to the 1.455 million people already diagnosed with the disease). Therefore, regulatory agencies including the US Food and Drug Administration have recently approved clinical trials using islets from pigs. However, the human body has an aggressive immune response against tissues from another species.
Scientists at Ben-Gurion University of the Negev’s Clinical Islet Laboratory have now discovered an approach that could solve this problem. It’s comprised of the combination of two safe drugs; one is a natural blood protein that fights inflammation, protecting transplanted animal islets from rejection.
“This approach may be applicable in the near future for the purpose of pig-to-human islet transplantation, a procedure currently examined in several clinical trials around the world,” said Lewis.
Researchers failed and tried again
The Israeli research team, led by Eli C. Lewis and including Efrat Ashkenazi, Boris M. Baranovski and Galit Shahaf, first determined that alpha-1 monotherapy protects same-species islet grafts from rejection. Next, they tested its effectiveness in protecting against rejection of non-human transplanted tissue.
At first, these experiments failed even when they tried increasing the dosage of alpha-1.
Then, the Israeli team studied graft samples at the microscopic level and made an educated guess that alpha-1 might be more effective against the strong immune response to inter-species rejection if used in tandem with another drug.
This “combination therapy” idea worked.
The method they added to the mix was temporary T-cell depletion, a procedure commonly used just prior to organ transplantation. On its own, temporary T-cell depletion worked only to delay graft rejection rather than prevent it.
But when the researchers used temporary T-cell depletion therapy on lab mice combined with alpha-1, transplanted islet grafts from a different species were accepted by the recipients, which received the temporary T cell depletion and a short course of alpha-1, and persisted to function even after treatment withdrawal.
Their study was financed by the Juvenile Diabetes Research Foundation, and could provide hope for people with type 1 diabetes around the world.