New ways to generate personalized blood stem cells could soon be developed to improve transplant outcomes for people with blood diseases such as leukemia and bone marrow diseases.
Researchers at Australia's Murdoch Children's Research Institute (MCRI) have developed a way to turn human cells, including hair, skin and blood cells, into hematopoietic stem cells.
Generating stem cells from a patient's own cells could one day eliminate the risks of serious illness and death associated with transplanting mismatched donor cells.
among them new research Published in nature biotechnologyscientists showed that hematopoietic stem cells can be successfully transplanted into mouse models.
Hematopoietic stem cells, located in the bone marrow, can produce all types of blood cells, from white blood cells in the immune system to red blood cells that carry oxygen and platelets, which are responsible for blood clotting.
“The ability to take any cell from a patient, reprogram it into stem cells, and turn it into blood cells that are specifically adapted for transplantation will have a profound impact on the lives of these vulnerable patients.” said lead author Elizabeth Ng. Group leader of MCRI's Blood Development Laboratory.
“We have developed a workflow to create transplantable blood stem cells that faithfully mimic human fetal blood stem cells. Importantly, these human cells can be created at the scale and purity required for clinical use. is.”
The researchers first determined how blood stem cells form during human embryonic development, allowing them to recreate the situation in a dish in the lab.
Their method involves taking human cells and using already well-understood processes to reprogram them into pluripotent stem cells, which have the ability to differentiate into any cell in the body.
The next step is to harvest pluripotent stem cells and provide the right environment and signals to transform them into hematopoietic stem cells (rather than a myriad of other potential cells), and to resolve this was the difficult part.
“We differentiate them by turning them into structures called embryoid bodies that float in culture,” Ng explained at a press conference for science journalists.
“By giving them growth factors…they differentiate and form an endothelium, and this endothelium produces blood.
“The actual process of harvesting pluripotent stem cells and making blood stem cells takes about 16 days. Now that we understand that, we can streamline that process as well.”
The laboratory-grown stem cells were cryopreserved, mimicking the procedure for human stem cell transplantation, before being injected into immunodeficient mice. Once inside the mouse, the bone marrow functions at a level similar to that of an umbilical cord hematopoietic stem cell transplant, which has proven to be a standard for success.
Hematopoietic stem cell transplantation is a risky procedure used to treat life-threatening blood diseases by harvesting healthy cells from a donor and transplanting them into a recipient.
“Mismatched donor immune cells from a transplant can attack the recipient's own tissues, leading to severe disease and death,” said co-author Andrew, group leader in the MCRI Blood Diseases Laboratory.・Mr. Elephanti says.
“The development of personalized, patient-specific blood stem cells can help prevent these complications, address donor shortages, and, in parallel with genome editing, correct the underlying causes of blood diseases. ”
The research team aims to conduct a phase 1 clinical trial to test the safety of transplanting lab-grown blood cells into humans within five years.
