Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2025; 17(6): 106272
Published online Jun 26, 2025. doi: 10.4252/wjsc.v17.i6.106272
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
Bo Zhang, Bao-Dong Gao, Yuan Su, Wen-Jing Mi, Tong-Xu Zeng, Fei-Fei Ma, Xiao-Qin Ha
Bo Zhang, Bao-Dong Gao, Yuan Su, Wen-Jing Mi, Tong-Xu Zeng, Fei-Fei Ma, Xiao-Qin Ha, Clinical Laboratory, The 940th Hospital of the PLA Joint Logistics Support Force, Lanzhou 730000, Gansu Province, China
Bo Zhang, Bao-Dong Gao, Yuan Su, Wen-Jing Mi, Tong-Xu Zeng, Fei-Fei Ma, Xiao-Qin Ha, Key Laboratory of Stem Cell and Gene Medicine, Lanzhou 730000, Gansu Province, China
Co-first authors: Bo Zhang and Bao-Dong Gao.
Author contributions: Zhang B and Gao BD performed the experiments, they contributed equally to this article as co-first authors; Zhang B and Ha XQ made substantial contributions to the conception and design of the study, drafting the article and critically revising it for important intellectual content; Zhang B, Su Y, Mi WJ, Zeng TX, and Ma FF acquired and analyzed the data; Ha XQ contributed to the discussion of the data, funding acquisition and supervision. All authors approved the final version for publication.
Supported by the Major Science and Technology Project of Gansu Province - Social Development Field, No. 25ZDFA007; Health Industry Research Funding Project of Gansu Province, No. GSWSKY2024-54; Youth Science and Technology Fund Program of Gansu Province, No. 21JR11RA014; National Natural Science Foundation of China, No. 81273568; Health Industry Research Funding Project of Gansu Province, No. GSWSKY2022-03; and Logistics Scientific Research Independent Project of the PLA.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the 940th Hospital of the PLA Joint Logistics Support Force (approval No. 2024KYLL314D).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the 940th Hospital of the PLA Joint Logistics Support Force (Protocol No. 2024KYLL312D).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Qin Ha, Clinical Laboratory, The 940th Hospital of the PLA Joint Logistics Support Force, No. 333 Nanbinhe Road, Qilihe District, Lanzhou 730000, Gansu Province, China. haxiaoqin2013@163.com
Received: February 21, 2025
Revised: April 2, 2025
Accepted: June 12, 2025
Published online: June 26, 2025
Processing time: 125 Days and 2.1 Hours
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

Core Tip: The effects of human umbilical cord mesenchymal stem cell (hUC-MSC) on platelet α-granules in rats during acute exposure to high-altitude hypoxia were assessed. hUC-MSCs significantly reduced platelet counts and plasma levels of von Willebrand factor, platelet factor 4, and beta-thromboglobulin, as well as the expression of CD62p on platelet surfaces. Additionally, hUC-MSCs improved platelet morphology and reduced pseudopodia formation and α-granule contents. These effects were mediated by activation of the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase signaling pathway. The findings suggest that hUC-MSCs may represent a promising preventive strategy against acute high-altitude-associated thrombosis, and provide empirical support for their expanded clinical application.