Protein pathway found to preserve blood stem cells before transplant
Researchers at the University of Zurich examined how activated protein C (aPC) affects human blood stem cells. Unlike thrombin, which acts through the same PAR1 receptor, aPC kept the cells in a quiescent state and reduced premature specialization. The findings, published in EMBO Molecular Medicine, suggest a way to maintain regenerative capacity during gene therapy processing.
Blood stem cells reside in bone marrow and generate blood and immune cells throughout life. They are used in marrow transplants and gene therapies, but laboratory processing before transplant can weaken regenerative capacity. University of Zurich researchers compared activated protein C with thrombin.
Both signal through PAR1, yet aPC kept human blood stem cells quiescent, dividing less and specializing less prematurely. A one-hour aPC treatment improved engraftment in mice, with more human blood cells and sustained blood formation after repeated transplantation. The study appeared in EMBO Molecular Medicine.
If these findings translate, patients with blood disorders undergoing stem cell transplants or gene therapy may benefit from better cell preservation and engraftment. Clinicians and laboratories could adopt brief aPC exposure during processing, potentially improving treatment reliability. However, human trials and long-term safety data may be needed before routine use. The impact may be greatest where stem cell availability or regenerative capacity limits therapy success.