Diabetes researchers pioneer islet cell xenotransplantation in primate studies
A team of researchers from the University of Alberta, the Yerkes National Primate Research Center of Emory University and the Emory Transplant Center has successfully transplanted insulin-producing neonatal porcine islet cells into monkeys, a procedure the researchers say represents a promising intermediate solution to the critical supply problem in clinical islet cell transplantation.
"Our work at the U of A and Emory, along with recent work at the University of Minnesota, is very exciting and shows that xenotransplantation in humans may soon be possible, thus solving the islet supply problem," says one of the study authors Ray Rajotte, a professor of Surgery at the University of Alberta.
The paper appeared in an advanced on-line publication of Nature Medicine, February 26, entitled "Long-term survival of neonatal porcine islets in non-human primates by targeting co-stimulation pathways." The work follows on the heels of similar work published last week by University of Minnesota researchers; those researchers used islets isolated from adult pig pancreases.
Neonatal islets were produced in Edmonton using a procedure Drs. Greg Korbutt and Rajotte developed in 1995. The pig islets were sent to the Yerkes Research Center for transplantation into diabetic rhesus macaques using an anti-rejection protocol developed by Drs. Christian Larsen and Kenneth Cardona of the Yerkes Research Center and the Emory Transplant Center. The isolation method developed by the U of A researchers is simple and reproducible with the neonatal pig islets having some growth potential post-transplant, considered a major advantage over adult pig islets.
The diabetic animals were treated with a CD28/CD154 co-stimulation blockade-based immunosuppressive regimen, and achieved sustained insulin independence (median survival >140 days with one animal now at 300 days) without evidence of porcine endogenous retrovirus (PERV) dissemination. "This represents a major step forward and proves neonatal porcine islets can correct diabetes long-term in primates," said Drs. Korbutt and Rajotte.
"To meet the needs of the millions suffering from type 1 diabetes, we must find new donor sources to allow large-scale application of islet cell transplantation in humans," said Dr. Larsen. "While there is much work to be done these studies suggest that the rejection response to porcine islets can be surmounted."
"The next step is to prove that these neonatal porcine islet cells could become a source for human transplantation," said Dr. Rajotte. "Its hoped that within the next three to five years, we will be transplanting patients with pig islets once we prove that it is safe."
Using a relatively simple and reproducible method of obtaining large numbers of islets from neonatal pig pancreata developed at the U of A, the researchers then transplanted islets comprised of endocrine and endocrine precursor cells into the monkeys. In vivo, these cells have been shown to proliferate, differentiate and reverse hyperglycemia in immunodeficient diabetic mice and allogeneic out-bred pigs.
However, humans and Old World primates have naturally occurring antibodies that are directed against antigens that can cause hyperacute or acute humoral rejection. To combat that, the researchers administered an anti-IL-2 receptor and anti-CD154 (H106) antibody, while maintaining immunosuppression using sirolimus and belatacept (a second-generation high affinity derivative of CTLA4-Ig)9-11 on diabetic rhesus macaques transplanted with neonatal porcine islets.
Michael Robb | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...