Blood stem cell breakthrough could transform bone marrow transplants

World first breakthrough could lead to improved, personalised treatments for children with leukaemia and bone marrow failure disorders

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) in Melbourne, Australia with support from academics at the University of Birmingham has been published in Nature Biotechnology. The breakthrough 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.

This new discovery was supported by work conducted by a PhD student (Alexander Maytum) from the research group of Prof Constanze Bonifer at the University of Birmingham which provided an essential clue for how to generate human blood stem cells capable of reconstituting the entire blood system in a dish. The data from the Bonifer team showed that the precisely timed addition and withdrawal of a specific growth factor in stem cell cultures was decisive for this process.

Professor Constanze Bonifer, Emeritus Professor of Experimental Haematology at the University of Birmingham and co-author of the study said:

“This is a remarkable discovery that could lead to significant improvements in how leukaemia and bone marrow failure disorders are treated in the future. The contribution by the University of Birmingham team has greatly improved the efficiency of creating a paradigm shifting blood stem cell that can overcome some of the issues with blood stem cell transplant treatments currently in use.”

Dr Elizabeth Ng, Associate Professor at the MCRI who led the study said the team had made a significant discovery in human blood stem cell development, paving the way for 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.”

Proven mark of success

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 thus mimicking the preservation process of donor blood stem cells before being transplanted into patients.

Professor Andrew Elefanty from MCRI 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.

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. Work in the Bonifer lab was funded by the BBSRC and published in Edginton-White et al., 2023, Nature Communication (PMID: 36650172)