Improving Hematopoietic Stem Cell Transplants
One of the causes of immune system aging is the growing dysfunction of hematopoietic stem cell populations, responsible for the production of immune cells. While some of this degeneration comes from the aging of the bone marrow niche, some it appears to be intrinsic to the cells themselves, and thus there may be benefits to be found in transplantation of functional hematopoietic stem cells derived from a patient's own cells. This would be the case if these cells could be made to reliably survive and engraft in any reasonable number, however. That is a challenging prospect, but it is worth keeping an eye on the cancer field, where transplantation of donor stem cells is used to attack leukemias, for signs of promising advances such as the one noted here.
Hardly a day goes by without someone receiving an infusion of healthy donor-derived hematopoietic stem cells (HSCs) to replace those lost or damaged by disease. But the types of stem cells contained in such a transplant are not all the same. The majority are "short-term" HSCs. These cells can give rise to all manner of white blood cells, thus offering a reprieve from cancer or disease. But the cells have limited capacity for self-renewal, a biological weakness that constrains the duration of their therapeutic benefit.
A different population of rare stem cells has the potential for prolonged reconstitution of the blood-forming system. These "long-term" HSCs can both sustain the stem cell pool and differentiate into their short-term kin, which makes them ideal from a therapeutic standpoint. But long-term HSCs have their own drawback: they are not particularly adept at engraftment, the process of taking root in recipient individuals - and researchers have now discovered why.
Researchers showed that, compared to short-term HSCs, the reduced expression of key adhesion molecules in long-term HSCs explained their poor engraftment ability. The researchers then found a type of drug commonly used to treat diabetes; when added to long-term HSCs, this drug altered the dynamics of cell surface adhesion molecules in ways that improved uptake of the cells in mice. Another type of adhesion-targeted treatment also augmented the engraftment potential of short-term HSCs - and, as an added bonus, it made the cells behave more like their long-term counterparts. Researchers next hope to test the strategy with human stem cells and human recipients.
Link: https://discovery.kaust.edu.sa/en/article/1270/sticky-stem-cells-make-for-better-transplants