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Home Science News Cancer

Blood stem cell breakthrough could transform bone marrow transplants

September 2, 2024
in Cancer
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Melbourne researchers have made a world first breakthrough into creating blood stem cells that closely resemble those in the human body. And the discovery could soon lead to personalised treatments for children with leukaemia and bone marrow failure disorders.

Melbourne researchers have made a world first breakthrough into creating blood stem cells that closely resemble those in the human body. And the discovery could soon lead to personalised treatments for children with leukaemia and bone marrow failure disorders.

The research, led by Murdoch Children’s Research Institute (MCRI) and published in Nature Biotechnology, has  overcome a major hurdle for producing human blood stem cells, which can create red cells, white blood cells and platelets, that closely match those in the human embryo.

MCRI Associate Professor Elizabeth Ng said the team had made a significant discovery 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.

“Prior to this study, developing human blood stem cells in the lab that were capable of being transplanted into an animal model of bone marrow failure to make healthy blood cells had not been achievable. We have 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, immune deficient mice were injected with the lab engineered human blood stem cells. It found the blood stem cells became functional bone marrow at similar levels to that seen in umbilical cord blood cell transplants, a proven benchmark of success. 

The research also found the lab grown stem cells could be frozen prior to being successfully transplanted into the mice. This mimicked 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 and white blood cells are our immune defence, while platelets cause clotting to stop us 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 the normal blood stem cells found in our bodies we can understand and develop personalised treatments for a range of blood diseases, including leukaemias and bone marrow failure.”

MCRI Professor Andrew Elefanty said while a blood stem cell transplant was often a key part of lifesaving treatment for childhood blood disorders, not all children found 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 personalised, patient-specific blood stem cells will prevent these complications, address donor shortages and, alongside genome editing, help correct 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 anaemia, a rare and serious blood disorder where the body stops producing enough new blood cells.

Riya’s family, including parents Sonali and Gaurav Mahajan, were in India at the time 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 anaemia. 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 return. 

“Once they were able to stabilise her, we were given a two-day window to fly her to Australia to be hospitalised,” 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 amount of transfusions she was needing to have and the concerns around possible long-term complications.”

Sonali said 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. 

Following the bone marrow transplant in June last year, Riya remained in 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, 14, said after a painful few years she was now 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 leukaemia and bone marrow failure disorders is life changing.”

Prof Elefanty, Prof Stanley and Associate Professor Ng are also Principal Investigators at the Melbourne node of the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), a global consortium, which aims to pave the way for future stem cell-based treatments.

Researchers from the University of Melbourne, Peter MacCallum Cancer Centre, University of California Los Angeles, University College London and the University of Birmingham also contributed to the findings.  

Publication: Elizabeth S. Ng, Gulcan Sarila, Jacky Y. Li, Hasindu S. Edirisinghe, Ritika Saxena, Shicheng Sun, Freya F. Bruveris, Tanya Labonne, Nerida Sleebs, Alexander Maytum, Raymond Y. Yow, Chantelle Inguanti, Ali Motazedian, Vincenzo Calvanese, Sandra Capellera-Garcia, Feiyang Ma, Hieu T. Nim, Mirana Ramialison, Constanze Bonifer, Hanna K. A. Mikkola, Edouard G. Stanley and Andrew G. Elefanty. ‘Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells,’ Nature Biotechnology. DOI: 10.1038/s41587-024-02360-7

*The content of this communication is the sole responsibility of MCRI and does not reflect the views of the NHMRC.

Available for interview:

Associate Professor Elizabeth Ng, MCRI Group Leader, Blood Development

Professor Andrew Elefanty, MCRI Group Leader, Blood Development

Professor Ed Stanley, MCRI Deputy Stem Cell Medicine Theme Director and Group Leader, Immune Development

Sonali and Gaurav Mahajan whose daughter Riya, 14, had aplastic anaemia, requiring a bone marrow transplant



Journal

Nature Biotechnology

DOI

10.1038/s41587-024-02360-7

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Long-term engrafting multilineage hematopoietic cells differentiated from human induced pluripotent stem cells

Article Publication Date

2-Sep-2024

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