Zhang B, Gao BD, Su Y, Mi WJ, Zeng TX, Ma FF, Ha XQ. Human umbilical cord mesenchymal stem cells reduce platelet α-granule release in rats via the AKT/MEK/ERK pathway during acute exposure to high-altitude hypoxia. World J Stem Cells. 2025 Jun 26;17(6):106272. doi: 10.4252/wjsc.v17.i6.106272. PMID: 40585956; PMCID: PMC12203129.
Abstract
BACKGROUND
While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk, preventive measures are currently limited. Recently, human umbilical cord mesenchymal stem cell (hUC-MSC) transplantation has been found effective in preventing and treating various clinical conditions, including thrombotic diseases. Platelets are crucial for thrombus formation, and their α-granules are key determinants of platelet function. However, little is known about the influence of hUC-MSCs on platelet α-granules.
AIM
To investigate the influence of hUC-MSCs on platelet α-granules in rats during acute exposure to high-altitude hypoxia.
METHODS
Rats were assigned to three groups, namely, low-altitude, high-altitude, and hUC-MSC-treated groups. The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m. Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa. hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions. Aortic blood was collected after three days to assess platelet counts and morphology and α-granule release.
RESULTS
Compared to the low-altitude group, the high-altitude group exhibited significantly higher platelet counts, plasma levels of von Willebrand factor, platelet factor 4, beta-thromboglobulin, as well as surface P-selectin (CD62p) and p-protein kinase B, p-mitogen-activated protein kinase, and p-extracellular-signal regulated kinase expression in platelets. Platelet morphology in the high-altitude group was irregular, with extended pseudopodia and increased α-granule densities. However, these changes were not apparent in the hUC-MSC-treated group.
CONCLUSION
Acute exposure to high-altitude hypoxia increased platelet counts, altered platelet morphology, and increased α-granule density and release. These effects were mitigated by hUC-MSC treatment, mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway. The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis, providing an experimental foundation for the development of clinical applications.
Keywords: Human umbilical cord mesenchymal stem cells, High-altitude, Hypoxia, Platelets, Platelet α-granules
