The aging population is more prone to blood clotting diseases, such as strokes and cardiovascular disease, due to the hyperreactivity of platelet cells. UC Santa Cruz Professor Camilla Forsberg and her research group have discovered a distinct secondary population of platelets that appears with aging and has unique molecular properties. These platelets are easier to target with medication, and the researchers have traced their development pathway from stem cells to mature platelet cells. Their findings were published in the journal Cell, shedding new light on why aging individuals are at a higher risk for excessive blood clotting.
Platelet dysregulation occurs when platelets are either hyperreactive or underperforming, leading to issues with bleeding and clotting. All blood cells originate from hematopoietic stem cells and follow a differentiation pathway to become platelets, red blood cells, or white blood cells. While hematopoietic stem cells decline with age, the researchers found a “shortcut” pathway in aged mice that produces hyperreactive platelets straight from megakaryocyte progenitors. This age-specific stem cell pathway is a groundbreaking discovery in the field.
The secondary population of hyperreactive platelets in aged mice starts to appear around midlife and increases with aging. Surprisingly, the trigger for this pathway is not the aging environment itself, as transferring young stem cells to an aged environment did not induce the shortcut pathway. This resilience of one population of platelets to aging highlights the importance of understanding differentiation pathways, rather than just environmental factors, in blood clotting diseases.
The existence of this secondary population of platelets opens up new possibilities for targeting and regulating these problematic cells through their stem cells. This could lead to more effective treatments for clotting-related symptoms using existing medications like Aspirin. By identifying which population of stem cells is more sensitive to these drugs, researchers can tailor therapies to individual patients based on the type of platelets they produce. The UCSC researchers are also working on identifying this secondary population of platelets in human cells with additional funding support.
Collaborators on this research included experts in applied mathematics and medical professionals, as well as current and former scholars at the Institute for the Biology of Stem Cells. The ongoing research aims to manipulate and control the shortcut pathway in mouse models to improve our understanding of blood clotting diseases and develop more targeted treatments. By focusing on upstream cells like hematopoietic stem cells and megakaryocyte progenitors, researchers hope to revolutionize how we approach blood thinning medications and improve outcomes for patients with clotting disorders.