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.

Image: Associate Professor Elizabeth Ng

“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.

Image: Professor Ed Stanley

“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.

Image: Professor Andrew Elefanty

“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.

Due to the condition, Riya needed regular platelet and blood transfusions to get her blood cell count up.

Image: Riya

A bone marrow transplant was recommended due to the amount of transfusions she was having and the concerns around possible long-term complications.

But they struggled to find a perfectly matched donor. Despite being a half match, Riya’s mother, following specialist advice, became her donor. 

Read more about Riya’s recovery from a bone marrow transplant.

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

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About Murdoch Children’s Research Institute

Murdoch Children's Research Institute is the largest child health research institute in Australia committed to making discoveries and developing treatments to improve child and adolescent health in Australia and around the world. They are pioneering new treatments, trialling better vaccines and improving ways of diagnosing and helping sick babies, children and adolescents. It is one of the only research institutes in Australia to offer genetic testing to find answers for families of children with previously undiagnosed conditions.

Funding

The study was supported by the Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, supported by Novo Nordisk Foundation grant number NNF21CC0073729 (A.G.E., E.S.N., J.Y.L., G.S., H.E., R.S., S.S., F.F.B., T.L., H.T.N., M.R., E.G.S., N.S., A.Maytum, R.Y.Y., C.I., C.B.). CSL Innovation supported this study through a collaborative research agreement with Murdoch Children's Research Institute (A.G.E., E.S.N., E.G.S., J.Y.L., G.S., R.Y.Y., C.I.). This study was also funded by the National Health & Medical Research Council of Australia (NHMRC) through research fellowships GNT1117596 (A.G.E) and GNT1079004 (E.G.S.), and grants awarded to A.G.E. and E.G.S. (GNT1068866, GNT1129861) (F.F.B, T.L.), to E.S.N. (GNT1164577, GNT2012936) (H.E., N.S.), to A.G.E (GNT2012535) (J.Y.L., G.S., R.S., F.F.B., A.Maytum, C.B.) and to E.G.S. (GNT1186019) (S.S., T.L., A.Motazedian). Joint funding from the California Institute for Regenerative Medicine and the NHMRC were awarded to H.K.A.M, A.G.E and E.G.S (RT3-07763) (A.G.E., E.S.N., E.G.S., H.K.A.M., T.L., V.C.). R.S was supported by a Hawkesbury Canoe Classic PhD Scholarship through The Arrow Bone Marrow Transplant Foundation (R.S.). S.C.-G. was supported by a Swedish Research Council International Postdoctoral Fellowship grant (IPD2 2018-06635) (S.C.-G.). Work in C.B.'s laboratory was funded by a grant from the Biotechnology and Biological Sciences Research Council (BBSRC) (BB/R014809/1) (C.B.). H.K.A.M was supported by NIH 1RO1DK125097-01 (H.K.A.M., V.C., S.C.-G.), the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Interim Research Award and Innovation Awards, and Jonsson Cancer Center Foundation Award. Funding is acknowledged by the Australian Research Council Special Research Initiative in Stem Cells (Stem Cells Australia), the Stafford Fox Medical Research Foundation, the Victorian Government’s Operational Infrastructure Support Program and the Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme (NHMRC IRIISS).