Photo by Louis Reed on Unsplash
Photo by Louis Reed on Unsplash

NEWS BRIEFING: Lab-made stem cells could transform bone marrow transplants, mouse study suggests

Embargoed until: Publicly released:
Peer-reviewed: This work was reviewed and scrutinised by relevant independent experts.

Experimental study: At least one thing in the experiment was changed to see if it had an impact on the subjects (often people or animals) – eg: changing the amount of time mice spend on an exercise wheel to find out what impact it has on weight loss.

Animals: This is a study based on research on whole animals.

Cells: This is a study based on research in micro-organisms, cells, tissue, organs or non-human embryos.

Aussie researchers have created blood stem cells in the lab that closely resemble those found in the human body – a finding that could lead to improved, personalised treatments for children with leukaemia and bone marrow failure disorders. In the study, the team used mice lacking an immune system and injected them with lab-engineered human blood stem cells. These stem cells became functional bone marrow at similar levels to that seen in umbilical cord blood cell transplants – a benchmark of success. The lab-grown stem cells could also be frozen prior to being successfully transplanted into mice – mimicking the preservation process that happens before human patients receive these transplants.

Journal/conference: Nature Biotechnology

Organisation/s: Murdoch Children's Research Institute (MCRI), The University of Melbourne, Peter MacCallum Cancer Centre

Funder: 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).

Media release

From: Murdoch Children's Research Institute (MCRI)

The briefing will discuss the following issues:

  • Key challenges to producing blood stem cells in the lab
  • How this new development could tackle the unique challenges of producing blood stem cells
  • What this research could mean for people with leukaemia and bone marrow failure disorders

Speakers:

  • Associate Professor Elizabeth Ng, Murdoch Children’s Research Institute Group Leader, Blood Development
  • Gaurav Mahajan and his daughter Riya, 14, who had aplastic anaemia and received a bone marrow transplant

Also available for questions:

  • Professor Andrew Elefanty who is Murdoch Children’s Research Institute Group Leader, Blood Development
  • Professor Ed Stanley, who is Murdoch Children’s Research Institute Group Deputy Stem Cell Theme Director and Group Leader, Immune Development

Date: Tue 20 Aug 2024
Start Time: 10:00am AEST
Duration: Approx 45 min 
Venue: Online - Zoom

Briefing recording available below

MCRI Media Release:

Blood stem cell breakthrough could transform bone marrow transplants

Research at a Glance:

  • A team led by Murdoch Children’s Research Institute (MCRI) has created blood stem cells in the lab that closely resemble those in the human body.
  • The world first breakthrough could lead to improved, personalised treatments for children with leukaemia and bone marrow failure disorders
  • The study has overcome a major hurdle for producing human blood stem cells, which create red cells, white blood cells and platelets, that closely match those in the human embryo
  • The researchers stated the significant findings paved the way for patient specific, lab grown cells to be used in blood stem cell and bone marrow transplants

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, ended up being 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 suspectable to infections. Riya only recently started to be revaccinated.

“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.

Attachments:

Note: Not all attachments are visible to the general public

News for:

Australia
International
VIC

Multimedia:

  • B-roll

    Attribution: Murdoch Children's Research Institute

    Permission Category: Free to share (must credit)

    Last Modified: 28 Aug 2024 1:36pm

    Download video file: B-roll

    Note: High resolution video files are only available for download here by registered journalists who are logged in.

Show less
Show more

Media contact details for this story are only visible to registered journalists.