At present, cell transplantation therapy is limited because transplant recipients are forced to take powerful immunosuppressant medications that have toxic side effects and raise the risk of infection. This advance in mice, described in the online version of Gene Therapy, could pave the way for routine use of cell transplants as a therapy for type 1 diabetes in humans.
Type 1 diabetes is an incurable autoimmune disease in which the immune system mistakenly destroys the body’s own pancreatic beta cells. Beta cells produce insulin, which breaks down sugar, or glucose, for use by the body. Without these cells, too much glucose builds up in the blood. High blood glucose levels damage cells and can eventually lead to complications such as heart disease, kidney disease, blindness, and premature death.
Type 1 diabetes affects up to 2.4 million Americans and can develop at any age, though it typically appears during childhood or adolescence. People with type 1 diabetes must closely monitor their blood glucose levels and take daily insulin injections for life.
A promising alternative to insulin injections is cellular transplantation, in which beta cells are harvested from cadavers and injected into the bloodstream of patients with diabetes; the new cells replace the recipients’ destroyed pancreatic beta cells. Although such transplants can control type 1 diabetes, recipients must take immunosuppressant medications in order to prevent rejection of these beta foreign cells. “Ultimately, even with immunosuppressive therapy, most of these individuals end up rejecting the transplanted cells,” says the study’s principal investigator, Harris Goldstein, M.D., professor of pediatrics and of microbiology & immunology at Einstein.
In this study, Dr. Goldstein and his colleagues devised a way to make foreign beta cells invisible to a transplant recipient’s immune system, dramatically protecting them from rejection. They did so by harnessing the innate ability of adenoviruses to evade the body’s immune surveillance system. (Adenoviruses infect tissues that line the respiratory tract, eyes, intestines, and urinary tract). After infecting cells, adenoviruses produce proteins that prevent the cells from signaling the immune system that they have been infected and should be destroyed. The viruses also produce proteins that can turn off a cell’s built-in self-destruct mechanism, which is usually triggered when something disturbs a cell’s internal functions.
The researchers began with a special line of insulin-producing beta cells, developed at Einstein, that were harvested from mice. When injected into diabetic mice, these foreign cells can restore normal glucose control, but only temporarily. The transplanted cells are soon destroyed by the mouse’s immune system and glucose levels begin to rise, returning to pre-transplant disease levels.
Dr. Goldstein and his colleagues genetically engineered these beta cells to include three adenoviral genes responsible for making immunosuppressive proteins. Diabetic mice that received these engineered foreign beta cells maintained normal glucose control for up to three months. In contrast, a control group of diabetic mice that received the regular foreign beta cells exhibited normal glucose control for just a few days.
“Clearly, the three proteins were not optimal, because ultimately the cells did get rejected,” says Dr. Goldstein. “We are now looking at other viral genes that also contribute to immune suppression and are trying to identify the best gene combination to use.”
Dr. Goldstein views the current experiment as a proof of concept. “We were able to demonstrate that genetically engineered beta cells can be made highly resistant to rejection and can basically correct diabetes. This technique could conceivably be applied to protect any type of cellular transplant from rejection.”
However, pancreatic cell transplantation could not help treat patients with type 2 diabetes. In this form of the disease, patients have fully functional beta cells but cells throughout their body become resistant to insulin.
The lead author of the paper is Tsoline Kojaoghlanian, M.D., assistant professor of pediatrics at Einstein. Other Einstein researchers involved in the study were Aviva Joseph, Antonio Follenzi, Jian Hua Zheng, Margarita Leiser, Norman Fleischer and Teresa DiLorenzo. An additional author is the late Marshall Horwitz, M.D., who conceived the strategy for the study. Dr. Horwitz was the Leo and Forchheimer professor and chair of microbiology & immunology as well as professor of pediatrics and of cell biology at Einstein.
Michael Heller | Newswise Science News
A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
21.08.2017 | Materials Sciences
21.08.2017 | Health and Medicine
21.08.2017 | Materials Sciences