Researchers in Melbourne have achieved a world first by successfully creating blood stem cells that closely resemble human tissue. This breakthrough may eventually lead to customized therapies for children suffering from bone marrow failure syndromes and leukemia.
The study, led by the Murdoch Children’s Research Institute (MCRI) and published in *Nature Biotechnology*, has overcome a significant hurdle in the production of human blood stem cells. These cells are capable of generating red and white blood cells, as well as platelets, that are highly similar to those found in human embryos.
MCRI Associate Professor Elizabeth Ng stated that the team had made a significant breakthrough in human blood stem cell development, paving the way for these lab-grown cells to be used in blood stem cell and bone marrow transplants.
“The ability to take any cell from a patient, reprogram it into a stem cell, and then turn these into specifically matched blood cells for transplantation will have a massive impact on these vulnerable patients’ lives,” she said.
“Before this study, developing human blood stem cells in the lab that could be transplanted into an animal model of bone marrow failure to produce healthy blood cells had not been achievable. We have now developed a workflow that has created transplantable blood stem cells that closely mirror those in the human embryo.
“Importantly, these human cells can be created at the scale and purity required for clinical use.”
In the study, immunodeficient mice were injected with the lab-engineered human blood stem cells. The blood stem cells became functional bone marrow at levels similar to those seen in umbilical cord blood cell transplants, a proven benchmark of success. The research also found that lab-grown stem cells could be frozen before being successfully transplanted into the mice, mimicking the preservation process of donor blood stem cells before being transplanted into patients.
MCRI Professor Ed Stanley said the findings could lead to new treatment options for a range of blood disorders.
“Red blood cells are vital for oxygen transport, white blood cells are our immune defense, and platelets cause clotting to stop us from bleeding,” he said. “Understanding how these cells develop and function is like decoding a complex puzzle.
“By perfecting stem cell methods that mimic the development of normal blood stem cells found in our bodies, we can understand and develop personalized treatments for a range of blood diseases, including leukemias and bone marrow failure.”
MCRI Professor Andrew Elefanty said that while a blood stem cell transplant is often a key part of life-saving treatment for childhood blood disorders, not all children find an ideally matched donor.
“Mismatched donor immune cells from the transplant can attack the recipient’s own tissues, leading to severe illness or death,” he said. “Developing personalized, patient-specific blood stem cells will prevent these complications, address donor shortages, and, alongside genome editing, help correct the underlying causes of blood diseases.”
Professor Elefanty said the next stage, likely in about five years with government funding, would be conducting a phase one clinical trial to test the safety of using these lab-grown blood cells in humans.
Riya was diagnosed at the age of 11 with aplastic anemia, a rare and serious blood disorder where the body stops producing enough new blood cells.
Riya’s family, including her parents Sonali and Gaurav Mahajan, were in India when she started to feel fatigued, rapidly lost weight, and developed bruises on her thighs.
“We took Riya for a simple blood test, her very first one. But as soon as the results came in, we were told to rush her to the emergency department due to her being so low on platelets and red blood cells,” Sonali said.
“Riya was originally diagnosed with leukemia because the symptoms are very similar to aplastic anemia. When we got the eventual diagnosis, it was a complete shock and a condition we had never heard of before.
“The doctors told us she had bone marrow failure, and she started needing regular platelet and blood transfusions to get her blood cell count up.”
Sonali said the family had already planned to return to Australia for Riya’s high school education, but the diagnosis fast-tracked the move.
“Once they were able to stabilize her, we were given a two-day window to fly her to Australia to be hospitalized,” she said.
“As soon as we got off the plane, we went straight to The Royal Children’s Hospital. Within days, Riya started therapy, but she never really responded to the medications.
“Eventually, a bone marrow transplant was recommended due to the number of transfusions she needed and concerns about possible long-term complications.”
Sonali said that over six months, they struggled to find a perfectly matched donor and were losing hope. Despite being a half match, Sonali, following specialist advice, became her daughter’s donor.
After the bone marrow transplant in June last year, Riya remained in the hospital for three months, where she had minor complications. Without a perfect donor match, Riya’s platelet count took more time to return to normal. She required longer immunosuppressive therapy and was more susceptible to infections. Riya only recently started to be re-vaccinated.
“She had a weakened immune system for a long time after the transplant, but thankfully, once she was discharged from the hospital, she hasn’t needed another transplant,” Sonali said.
Riya, now 14, said after a painful few years, she was feeling well, took hydrotherapy classes, and was glad to be back at school with her friends.
Sonali said the new MCRI-led research on blood stem cells was a remarkable achievement.
“This research will come as a blessing to so many families,” she said. “The fact that one day there could be targeted treatments for children with leukemia and bone marrow failure disorders is life-changing.”
(With ANI Inputs)
