Blood stem cell expansion expands treatment options for cancer patients

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Image courtesy of the Stower’s Institute

Bone marrow transplants have been used for decades to treat various types of cancers such as leukemia and multiple myeloma, as well as other blood disorders such as anemia.

Our bone marrow is responsible for making hematopoietic stem cells (HSCs), which develop into mature blood cells, like white cells (which fight infection) and red cells (which carry oxygen throughout our body). In different types of blood disorders, blood cell production is either impaired or abnormal. In leukemia for example, the body produces abnormal white blood cells that survive better then outgrow the normal white cells, thus impairing the individual’s ability to fight infection. Bone marrow transplants, which involves replacing the diseased marrow with healthy marrow from a donor, can be incredibly effective for these types of disease. Survival from certain blood cancers increased from basically zero to around eighty-five percent after the advent of bone marrow transplant therapy.

While extremely effective when successful, bone marrow transplants do not work for everyone and finding a match can be difficult. For example, only 30% of patients are able to find a match in their families, because of the strict requirements that must be fulfilled be a bone marrow match. Stem cells from umbilical cord blood, on the other hand, are much more likely to match a patient, because of the generally less stringent requirements to be a match. The amount of cord blood (nearly two whole cords worth of blood) needed to satisfy an adult patient’s transplant requirements, however, are significant, and can be a limiting factor in the efficiency and effectiveness of this approach. New research from Lingheng Li’s lab at the Stower’s Institute for Medical Research at the University of Kansas has found a possible solution to this problem.

In a study published in Cell Research, Li’s group found a way to increase the number of adult stem cells isolated from cord blood, which could reduce the number of cords needed per treatment. By eliminating a protein called Ythdf2 in mice, they observed global expansion of HSCs. Normally, this protein is responsible for preventing expression of genes involved in promoting HSC expansion. Importantly, the researchers found that the HSC expansion stimulated by elimination of Ythdf2 did not lead to other abnormalities in the resulting HSCs and did not affect the ability of these HSCs to produce different types of blood stem cells down the road. Dr. Li believes that this type of approach can be applied to other types of stem cell treatments as well.

Dr. Joseph McGuirk, another professor at the University of Kansas who was not directly involved with this study, indicates the importance of this work:

“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. 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.”

CIRM is funding work in this area too. We are supporting a late stage preclinical project with AngioCrine Biosciences which is using expanded cord blood stem cells. They hope to create an effective and, safe option for the treatment of debilitating blood diseases such as leukemia and lymphoma.

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