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!
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy