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!
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
Chlamydia: How bacteria take over control
28.03.2017 | Julius-Maximilians-Universität Würzburg
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Physics and Astronomy
28.03.2017 | Health and Medicine
28.03.2017 | Life Sciences