“Sticky” Stem Cells Facilitate Better Transplants

Within all transplants, it’s a concern how the body’s own immune system will react to forms of medical intervention, also known as engraftment. Sometimes, the recipient’s cells identify the transplanted tissue as foreign and attack them. Researchers from KAUST investigated how these cells, specifically blood-forming stem cells from humans, can be efficiently transferred from healthy donors to patients with leukemia and other blood disorders.

Their work, published in the journal Blood Advances, identified two different drug treatments that enhanced the cell adhesion activity of molecules within hematopoietic stem cells (HSCs). This allowed the stem cells to enter the recipient mouse’s bloodstream more efficiently and start making new blood. 

“This is a crucial finding,” says study author Asma Al-Amoodi, a Ph.D. student in Jasmeen Merzaban’s lab at KAUST. “Such information is indispensable for researchers and clinicians, as it will guide which stem cell populations we select for and which treatments we may use prior to injection in order to increase the success and outcomes of the transplantation process.”

While donor-derived HSCs have been used therapeutically for many decades, the subdivisions of HSCs makes predicting their transplant efficacy challenging. Most HSCs are known as “short-term” and typically give rise to white blood cells. However, these cells have limited self-renewal capabilities, making them less than ideal for therapeutic intervention with diseases like cancer.

An entirely different population of stem cells, known as “long-term” HSCs, can sustain the stem cell pool and differentiate into short-term HSCs as necessary, making them flexible therapeutic targets. KAUST researchers investigated these long-term HSCs in more detail for their work, mainly why these stem cells aren’t as adept at engraftment.

The group discovered that long-term HSCs expressed fewer cell adhesion molecules than short-term HSCs, resulting in poorer engraftment abilities. The team identified a drug typically used to treat diabetic patients that altered the dynamics of cell surface adhesion molecules within long-term HSCs, improving their uptake and engraftment in mice.

Merzaban hopes to test this strategy with human stem cells and recipients for future work. “The results of our study suggest that by enhancing the adhesion of these stem cells, we could improve the ability of both types of HSC populations to migrate, engraft and provide functional blood cells to patients,” she says.