New treatments have emerged to temporarily prevent stem cells from dying during hematopoietic stem cell (HSCs) transplants.
Researchers from the University Medical Center of Freiburg in Germany have taken a new approach to allow those needing transplants, including those suffering from leukemia and lymphoma, to be treated using fewer donor stem cells while limiting potential side effects.
Hematopoietic stem cells give rise to the different cell types found in blood and can be used to treat several diseases, including multiple myeloma, leukemia and sickle cell anemia.
They are harvested from a suitable donor and then transplanted into a patient. After establishing themselves in the bone marrow, they can generate healthy blood cells.
However, this puts stress on the HSCs, causing many of them to die before they can successfully ensconce themselves in the patient’s bone marrow, limiting the effectiveness of the transplantation and delaying the resumption of blood cells formation, while increasing the risk of infection or bleeding or causing the transplant to fail completely.
The researchers improved the efficiency of HSCs transplants in mice by permanently inhibiting a pair of proteins called BIM and BMF.
However, the mice soon developed an autoimmune disease or lymphoma because the HSCs and the blood cells they produce did not die when they were supposed to.
“Thus, inhibiting apoptosis transiently during the stressful period of transplantation could be an attractive strategy to improve transplantation outcome without increasing the risk of long-term adverse effects,” Dr. Miriam Erlacher of the University Medical Center of Freiburg, said in a statement.
The research team was able to isolate the HSCs from mice and infect them with a genetically engineered adenovirus that transiently produces BCL-XL—a human protein that inhibits BIM and BMF.
The infected HSCs showed resistance to apoptosis—the death of cells that occurs as a normal and controlled part of an organism’s growth or development—for the seven to nine days that BCL-XL was expressed.
The transplanted HSCs only expressed BCL-XL for a few days without promoting the formation of lymphomas in recipient animals.
The researchers also developed an alternative approach by purifying BCL-XL that could be introduced directly into isolated HSCs, which also provides temporary protection from apoptosis and improves the cells’ ability to undergo transplantation.
“Our findings suggest that transiently inhibiting apoptosis by manipulating donor HSCs increases the fitness of these cells without elevating the risk of adverse pathology,” Erlacher said. “Transient apoptosis inhibition is therefore a promising approach to reduce the risk of graft failure and improve HSC transplantation outcomes.”
