Volume : 12, Issue : 11, November – 2025
Title:
HYPOXIA-DRIVEN PROLIFERATION AND MORPHOLOGICAL REMODELING IN HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS
Authors :
Moshera Alansi, Mohammed Gamah, Maged Almezgagi, Huang Pan, Yougang Ma, Xiaobo Wang, Emad Shamsan, Minmin Wei, Ting Wang Ya, Lan Ma△
Abstract :
Background: Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are widely used in regenerative medicine due to their multipotency, immunomodulatory properties, and paracrine effects. Oxygen tension in the cellular microenvironment plays a pivotal role in regulating MSC behavior, yet the specific effects of hypoxia on hUCMSC morphology and proliferation remain incompletely understood.
Methods: Passage 4 hUCMSCs were cultured under normoxic (21% O₂) or hypoxic (1% O₂) conditions for 48 h. Cell proliferation was assessed via direct cell counting and confluence-based imaging, while morphological changes were evaluated through phase-contrast microscopy and quantitative analysis of cell length and area using ImageJ. All experiments were performed in triplicate.
Results: Hypoxic preconditioning induced distinct morphological changes, including increased cell length (160 ± 20 µm vs. 120 ± 15 µm; p < 0.05) but decreased cell area (1500 ± 180 µm² vs. 1800 ± 200 µm²; p < 0.01) compared to normoxia. Importantly, hypoxia significantly accelerated proliferation rates and confluence. Quantitative viability assays were not performed and should be included to confirm that proliferation increases occur without loss of viability. These findings suggest that low oxygen tension promotes both cell elongation and changes in cell size and enhanced proliferative activity.
Conclusion: Exposure to 1% O₂ for 48 h modulates hUCMSC morphology and growth dynamics by enhancing proliferation. Hypoxic preconditioning emerges as a practical strategy to optimize MSC characteristics for regenerative applications. These results provide a foundation for further studies on functional enhancements, including migration, paracrine secretion, and therapeutic efficacy.
Cite This Article:
Please cite this article in press Lan Ma et al., Hypoxia-Driven Proliferation And Morphological Remodeling In Human Umbilical Cord-Derived Mesenchymal Stem Cells, Indo Am. J. P. Sci, 2025; 12(11).
REFERENCES:
1. Ahani-Nahayati M, Niazi V, Moradi A, et al. Umbilical Cord Mesenchymal Stem/Stromal Cells Potential to Treat Organ Disorders; An Emerging Strategy. http://www.eurekaselect.com. Accessed September 11, 2025. https://www.eurekaselect.com/article/117741
2. Azari Z, Nazarnezhad S, Webster TJ, et al. Stem cell‐mediated angiogenesis in skin tissue engineering and wound healing. Wound Repair Regen. 2022;30(4):421-435. doi:10.1111/wrr.13033
3. Kan C, Chen L, Hu Y, et al. Microenvironmental factors that regulate mesenchymal stem cells: lessons learned from the study of heterotopic ossification. Histol Histopathol. 2017;32(10):977-985. doi:10.14670/HH-11-890
4. Xue Z, Liao Y, Li Y. Effects of microenvironment and biological behavior on the paracrine function of stem cells. Genes Dis. 2023;11(1):135-147. doi:10.1016/j.gendis.2023.03.013
5. Antebi B, Rodriguez LA, Walker KP, et al. Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells. Stem Cell Research & Therapy. 2018;9(1):265. doi:10.1186/s13287-018-1007-x
6. Zhuo H, Chen Y, Zhao G. Advances in application of hypoxia-preconditioned mesenchymal stem cell-derived exosomes. Front Cell Dev Biol. 2024;12. doi:10.3389/fcell.2024.1446050
7. Pulido-Escribano V, Torrecillas-Baena B, Camacho-Cardenosa M, Dorado G, Gálvez-Moreno MÁ, Casado-Díaz A. Role of hypoxia preconditioning in therapeutic potential of mesenchymal stem-cell-derived extracellular vesicles. World J Stem Cells. 2022;14(7):453-472. doi:10.4252/wjsc.v14.i7.453
8. Jin Y, Wu O, Chen Q, et al. Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3–ANAX2 Axis to Alleviate Intervertebral Disc Degeneration. Advanced Science. 2024;11(34):2404275. doi:10.1002/advs.202404275
9. Cheng J, Ruan X, Li Y, et al. Effects of hypoxia-preconditioned HucMSCs on neovascularization and follicle survival in frozen/thawed human ovarian cortex transplanted to immunodeficient mice. Stem Cell Res Ther. 2022;13:474. doi:10.1186/s13287-022-03167-6
10. Kuntjoro M, Hendrijantini N, Prasetyo EP, Agustono B, Hong G. Hypoxia-Preconditioned Human Umbilical Cord Mesenchymal Stem Cells Transplantation Ameliorates Inflammation and Bone Regeneration in Peri-Implantitis Rat Model. Eur J Dent. 2024;19(2):420-427. doi:10.1055/s-0044-1791530
11. Sun L, Zhu W, Zhao P, et al. Long noncoding RNA UCA1 from hypoxia-conditioned hMSC-derived exosomes: a novel molecular target for cardioprotection through miR-873-5p/XIAP axis. Cell Death Dis. 2020;11(8):1-16. doi:10.1038/s41419-020-02783-5
12. Chacko SM, Ahmed S, Selvendiran K, Kuppusamy ML, Khan M, Kuppusamy P. Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells. Am J Physiol Cell Physiol. 2010;299(6):C1562-C1570. doi:10.1152/ajpcell.00221.2010
13. Nisar H, Sanchidrián González PM, Brauny M, et al. Hypoxia Changes Energy Metabolism and Growth Rate in Non-Small Cell Lung Cancer Cells. Cancers (Basel). 2023;15(9):2472. doi:10.3390/cancers15092472
14. Pankajakshan D, Agrawal DK. Mesenchymal Stem Cell Paracrine Factors in Vascular Repair and Regeneration. J Biomed Technol Res. 2014;1(1):10.19104/jbtr.2014.107. doi:10.19104/jbtr.2014.107
15. Yang Y, Wu Y, Yang D, et al. Secretive derived from hypoxia preconditioned mesenchymal stem cells promote cartilage regeneration and mitigate joint inflammation via extracellular vesicles. Bioact Mater. 2023;27:98-112. doi:10.1016/j.bioactmat.2023.03.017




