Alternative signaling pathway improves transplantation of blood stem cells

Blood stem cells are responsible for producing the blood and immune cells necessary for a lifetime, making them crucial for bone marrow transplants and gene therapies. However, laboratory processing of these cells during treatment can diminish their regenerative abilities, reducing the success rate of these therapies. Researchers at the University of Zurich sought to find alternative signaling pathways to enhance blood stem cell function.

They focused on the protein activated protein C (aPC), comparing its effects to thrombin, another protein involved in blood clotting.

The study, published in EMBO Molecular Medicine, revealed that aPC helps maintain blood stem cells in a resting state, known as quiescence, which preserves their regenerative properties. This resting state is essential for the cells to divide less frequently, avoid premature differentiation into specialized blood cells, and retain their vital characteristics.

In contrast, thrombin promoted excessive differentiation, potentially reducing the cells' stem cell potential. Importantly, a one-hour treatment with aPC improved transplantability in an animal model, leading to more human blood cells being produced and a better ability to sustain blood formation even after repeated transplantations.

Furthermore, the research demonstrated that aPC treatment protected stem cells from activation by inflammatory signals, which would normally drive them out of their resting state. The findings suggest that signaling through activated protein C could be a promising strategy to preserve the quality and regenerative capacity of human blood stem cells. This approach may ultimately improve the success of stem cell transplants and gene therapies for patients with blood disorders.