A new discovery could lead to the adult stem cells from human umbilical cord blood (hUCB) becoming readily accepted in patients who undergo adult stem cell treatments for conditions like leukemia, blood disorders, immune system disease and other types of cancer but do not have an appropriate bone marrow match.
A team from the Stowers Institute for Medical Research have pinpointed a protein called Ythdf2 that impacts multiple targets and pathways involved in hematopoietic stem cell self-renewal.
“Life-saving bone marrow transplants have been the common practice for decades, but this doesn’t work for everybody,” Stowers Institute Investigator Linheng Li, PhD, the study lead, said in a statement.
The protein recognizes a particular type of modification in a group of mRNAs that encodes key transcription factors for hematopoietic stem cell self-renewal and promotes the decay of the mRNAs within cells.
The researchers knocked out the protein’s function in a mouse model or knocked down the Ythdf2 function in hUCB cells to increase the expression of the transcription factors and expand the hematopoietic stems cells—the major type of adult stem cells in hUCB.
The researcher’s observed that impairing Ythdf2 function did not alter the types of cells that were produced or lead to increased blood cell malignancies.
“Our approach of targeting Ythdf2 function using an RNA-based technique also helped avoid more persistent DNA-related changes such as mutations in epigenetic regulators,” Zhenrui Li, PhD, a predoctoral researcher at the University of Kansas Medical Center who is performing thesis research in the Linheng Li Lab and first author of the study, said in a statement.
Because the targeted protein is present in different kinds of stem cells, targeting it and discovering how it affects hematopoietic stem cells could be a safer approach to treat leukemia or cancer.
According to the U.S. Department of Health and Human Services, about 30 percent of patients have a bone marrow match available in their families, with more than 170,000 people in the U.S. expected to be diagnosed with a blood cancer this year.
Adult stem cells from umbilical cords are more likely to be a match for more people because of lesser compatibility requirements needed than with bone marrow transplants. However, adults need two cords’ worth of blood per treatment.
“This work represents a path forward by demonstrating the ability to reliably expand adult stem cells from umbilical cord blood in the laboratory without terminally differentiating the cells into more mature and relatively short-lived blood cells,” Joseph McGuirk, MD, professor of medicine and medical director of blood and marrow transplant at the University of Kansas Health System, who was not directly involved with the study, said in a statement.
“These findings represent a major advance in the field and have significant potential to improve the outcomes of thousands of children and adults who undergo umbilical cord blood transplantation every year.”
The study was published in Cell Research.