University of Minnesota Medical School researchers have discovered a method to quickly and exponentially grow regulatory T-cells – also known as "suppressor cells." The new process enables replication of the cells by tens of millions in several weeks, a dramatic increase over previous duplication methods. Historically, regulatory T-cells have been difficult to replicate.
The new technique will give patients a better chance of having a successful bone marrow or organ transplant, and will have profound implications for patients with autoimmune diseases such as lupus, type 1 diabetes, Crohn's disease and multiple sclerosis.
The use of the new replication technique has already shown promising effects in the treatment of acute graft-versus-host disease; a post-transplant condition in which T-cells from the donor's bone marrow recognizes a recipient's body as foreign, and tries to attack.
"When regulatory T-cells don't respond to inflammation quickly enough to suppress an immune system response, the patient's own immune response can do considerable harm after a transplant, injuring organs, joints and other tissues of the body," said Dr. Bruce Blazar, senior author of the study and Director of the Clinical and Translational Science Institute at the U of M.
Compounding the challenge is that humans have a limited supply of regulatory T-cells, Blazar said. So even if the immune system's cells respond appropriately, there may not be enough suppressor cells to stop errant reactions in time before the immune response causes widespread tissue damage.
Researchers felt that by developing a way to replicate the cells – which have been historically challenging to coax into high rates of duplication – they could increase transplantation success rates.
Between 30-40 percent of all related bone marrow transplant patients experience graft-versus-host disease, and between 10-30 percent of kidney transplants and 60-80 percent of liver transplant recipients experience acute rejection, according to the National Institutes of Health.
About the New Method
The immunology team, led by Blazar, developed a method to extract regulatory T-cells from blood and subsequently deliver the right combination of signals to make the cells replicate up to 50 million fold. Previous methods to duplicate these cells led to only 70-fold expansion at best.
The findings are published in the May 18 edition of Science Translational Medicine.
"The ability to deliver such large quantities of these cells to patients before they undergo transplantation significantly reduces the chances of graft versus host disease and rejection of a transplanted organ," Blazar said.
In animal models and in human clinical trials (where smaller doses of regulatory T cells were given to patients), Blazar's hypothesis came to fruition: Animals and patients became less likely to develop severe immune reactions that caused tissue damage.
The next step in Blazar's work is phase 1 human clinical testing headed by the U of M's Dr. John Wagner, a world renowned researcher who has been a leader in the field of blood and marrow transplantation. Wagner plans to lead a team of doctors who will administer increasing doses of regulatory T-cells before bone marrow transplants using Blazar's new expansion method.
"This is truly exciting and a major, major breakthrough with profound implications in the treatment of our patients," Wagner said. "If we can super charge patients' immune systems before we do a transplant, we hope to eliminate the chance of graft-versus-host disease or rejection of the transplanted organ. Furthermore, we hope to move these trials ahead quickly to treat autoimmune diseases which affect hundreds of thousands of people worldwide."
Alongside Drs. Blazar and Wagner, U of M assistant professor Dr. Keli Hippen, the lead investigator of the study, pushed this new technology forward.
Collaborators from the University of Pennsylvania provided the key cell lines that made the research possible. Penn scientists engineered artificial Antigen Presenting Cells (aAPCs) which massively expanded regulatory T-cells. The process by which they were replicated could be used to generate a master cell bank that could be used to treat a large number of patients, making therapy much more feasible and cost effective.
The study was funded by National Institutes of Health, the Leukemia and Lymphoma Society and the Childrens' Cancer Research Fund.
Nick Hanson | EurekAlert!
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences