In breakthrough, Israeli-led team activates dormant bone marrow cells for transplants
Using mRNA model made famous by COVID vaccine, researchers from Israel, US and Canada find protein to ‘awaken’ adult stem cells in mice; could significantly improve bone marrow transplant success rates
An international research team led by an Israeli scientist says it is the first in the world to find an innovative method to activate adult stem cells in the lab to use in bone marrow regeneration for transplant recipients.
The findings, published in the peer-reviewed journal Nature Immunology, represent a breakthrough that could significantly improve the success rates for patients who receive bone marrow transplants.
The innovation may help people who have undergone intensive chemotherapy or irradiation therapy who have lost many of their stem cells, as well as those with genetic blood disorders such as thalassemia — a hemoglobin deficiency — and hereditary anemia.
“Sometimes, even if a donor is a match for the person needing treatment, the donor doesn’t have enough stem cells for transplantation,” said Dr. Tomer Itkin from the Faculty of Medical and Health Sciences at Tel Aviv University and Sheba Medical Center, who led the study. “This new method significantly expands the available pool of stem cells for transplantation.”
The study, which was co-led by Sean Houghton of Weill Cornell Medical College and Hospital in New York, also involved a team of over two dozen researchers from Memorial Sloan Kettering Cancer Center, the University of Toronto Medical Center and other hospitals.
“We’re the first in the world to show that we have a way to program activation of adult stem cells,” Itkin told The Times of Israel by phone.
‘You need huge numbers’
Bone marrow — the soft tissue inside the bones — contains adult stem cells that constantly produce new blood cells, keeping the blood and immune system healthy.
But people with diseases such as leukemia, aplastic anemia and lymphoma are unable to regenerate their own blood. They need a bone marrow transplant from a donor with similar blood proteins.
Even with a suitable match, however, the transplant doesn’t always succeed because the new stem cells don’t grow. After chemotherapy, for example, patients are unable to restart their own blood cell production because of the depletion of their stem cell pool.
The challenge for bone marrow regeneration is that stem cells — highly active in umbilical cord blood and able to regenerate themselves — become “quiescent,” or dormant, in adult bone marrow, Itkin explained.
Some bone marrow donors are only able to provide a “very low yield of stem cells, which is not enough for transplantation,” he said.
For each kilogram a patient weighs, three million stem cells are needed for transplantation (or 1.36 million cells per pound).
“You need huge numbers,” said Itkin. That is where his research comes in.
Inspired by COVID
Itkin and the other researchers identified a key protein — the Fli-1 transcription factor — that activates these quiescent stem cells in the immune and the blood system.
Fli-1 “is actually a gene which is involved in leukemia,” Itkin said. “It stands for ‘Friend of Leukemia, Initiating Factor One.’”
The gene was originally discovered as a tumor-promoting gene, “so we cannot just over-express it without control,” he explained. “And then came the insight from COVID.”
Most COVID-19 vaccines are made from a modified mRNA molecule, which temporarily increases the production of a protein to fight the virus before it quickly disappears.
Using the same approach, the scientists introduced Fli-1 modified RNA into mice, which successfully roused the previously quiescent adult stem cells.
It was enough to “kick the cells into their activation state,” he said, “waking them up from their dormancy and to start being activated.”
The scientists conducted safety tests to check for mutations that might lead to leukemia. They didn’t find anything for half a year after transplantation into mice.
“The modified RNA disappeared from the system very quickly, and the protein levels went back to normal levels after few days,” Itkin said.
The team also transplanted Fli-1 modified human cells into the immune deficient mouse model and found the transplanted stem cells demonstrated an enhanced ability to integrate and restore blood production.
“This new method significantly expands the available pool of stem cells for transplantation,” the researcher said. “Additionally, the method can be used to treat patients who have undergone multiple rounds of chemotherapy or genetic therapy and have an insufficient number of their own healthy stem cells.”
Itkin said that he believes this type of research shouldn’t take more than five years to bring to clinical trial and then get FDA approval.
“This also opens up a lot of opportunities in other fields,” he said, including using the innovative method on tissues without stem cells.
“We showed it in the bone marrow,” Itkin said. “Now we’re thinking, okay, maybe we can also do it in the lungs, in the heart, in the brain, and many other tissues.”
No comments:
Post a Comment