A team of Australian researchers has developed a method to morph personalized stem cells into hematopoietic stem cells, something that would promise risk-free bone marrow transplants
For a myriad of blood and bone marrow-based diseases including leukemia, a bone marrow transplant is the best standard treatment option available.
However, risks abound with the procedure such as mismatched donor cells prompting attacks on the host’s own tissues, leading to inflammation and even death.
Conducted at the Murdoc Children’s Research Institute in Australia (MCRI), the team first performed the common procedure of taking human cells from the hair, skin, and nails, and using a process to reprogram them to morph back into ‘pluripotent’ or ‘multi-power’ stem cells.
Pluripotent cells are richly found in human embryos and infants and have the ability to take the form of any cell in the body. It’s been a decade since Nobel Prize winner Shinya Yamanaka found out how to change any cell in the body back into pluripotent stem cells.
The authors of the new study from MCRI explain that the next step—of turning pluripotent stem cells into hematopoietic stem cells—which can take any form of blood cell, has been difficult to discover, but if it could be standardized, then bone marrow transplants for sensitive individuals like childhood leukemia patients would have much better success rates.
“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,” says Elizabeth Ng, lead author of the study and Group Leader of the Blood Development Laboratory at MCRI.
“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.”
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“Importantly, these human cells can be created at the scale and purity required for clinical use,” Ng adds.
In their study, they not only managed to make this pluripotent-hematopoietic leap, but successfully froze the resultant stem cells before transplanting them into immune-deficient mice. The success they recorded was typical of the rare procedure that is used as the benchmark of success—an umbilical cord hematopoietic stem cell transplant.
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“By perfecting stem cell methods that mimic the development of the 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,” said MCRI Professor Ed Stanley.
His colleague, Dr. Andrew Elefanty, adds that manufacturing stem cells in this way solves additional problems as well.
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“Mismatched donor immune cells from the transplant can attack the recipient’s own tissues, leading to severe illness or death,” said Dr. Elefanty. “Developing personalized, patient-specific blood stem cells will prevent these complications, address donor shortages, and, alongside genome editing, help correct underlying causes of blood diseases.”
At the time this research and experimentation was ongoing, an 11-year-old girl named Riya was at MCRI receiving a bone marrow transplant from her mother Sonali, who was only a half-match. It took 3 years for her to recover to the point where she could go back to school, but there she and her family got to learn from Drs. Stanley and Ng what their research might do for children like her.
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