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World J Stem Cells. Sep 26, 2026; 18(9): 123933
Published online Sep 26, 2026. doi: 10.4252/wjsc.123933
Experimental study on ultrasound-targeted microbubble destruction promoting the proliferation, migration of human umbilical cord mesenchymal stem cells
Pan Zhang, Bo-Ya La, Man-Li Zhang, Burleshan Rewan, Ling-Yun Zhang, Xiao-Lin La
Pan Zhang, Man-Li Zhang, Burleshan Rewan, Ling-Yun Zhang, Xiao-Lin La, Reproductive Medicine Center, The First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
Bo-Ya La, State Key Laboratory of Reproductive Medicine and Offspring Health, Center of Clinical Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Man-Li Zhang, Xiao-Lin La, Xinjiang Medical University Clinical Medical Research Centre of Reproductive Diseases and Birth Defects Urumqi, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
Xiao-Lin La, Xinjiang Clinical Research Centre for Reproductive Immunology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
Xiao-Lin La, State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region, China
Co-first authors: Pan Zhang and Bo-Ya La.
Author contributions: Zhang P and La BY was in charge of experimental operation, manuscript preparation, data collection and summarisation, as well as statistic calculation, they contributed equally to this manuscript and are co-first authors; Zhang ML was in charge of research supervision and advice from this study, revised the draft; Rewan B was in charge of experimental operation; Zhang LY was in charge of data collection and summarisation; La XL supervised the paper’s final editing process, funded this project.
AI contribution statement: AI tools (Doubao/Deepseek) were used solely for linguistic refinement and formatting assistance. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions. All AI-generated outputs were critically reviewed and revised by the authors.
Supported by the Health Science and Technology Plan Project of the Autonomous Region - Innovative Research Project, No. 2025001CXKMYM650030870; Open Project of the State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, No. SKL-HIDCA-2024-GX2; and Tianshan Talents Leading Talent Project for Medicine and Health Care, No. TSYC202401A023.
Institutional review board statement: The study was reviewed and approved by the First Affiliated Hospital of Xinjiang Medical University Institutional Review Board (Approval No. 260414-09).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The raw RNA-seq data generated in this study are available from the corresponding author upon reasonable request. Researchers who wish to access the data should contact the corresponding author via email.
Corresponding author: Xiao-Lin La, Reproductive Medicine Center, The First Affiliated Hospital of Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, No. 137 South Liyushan Road, Xinshi District, Urumqi 830054, Xinjiang Uygur Autonomous Region, China.
909232905@qq.com
Received: June 3, 2026
Revised: July 12, 2026
Accepted: September 16, 2026
Published online: September 26, 2026
Processing time: 115 Days and 0.1 Hours
BACKGROUND
Enhancing the homing and migratory capacity of transplanted human umbilical cord mesenchymal stem cells (hUCMSCs) is critical for regenerative medicine. Ultrasound-targeted microbubble destruction (UTMD) is a non-invasive strategy with therapeutic potential; however, its optimal parameters and underlying mechanisms for promoting hUCMSC migration require further elucidation.
AIM
To investigate the effects of microbubble (MB) concentration and ultrasound duration on hUCMSC proliferation and migration and the C-X-C chemokine receptor type 4 (CXCR4) axis.
METHODS
MBs were characterized by optical microscopy and zeta potential analysis. hUCMSCs were identified by flow cytometry, immunofluorescence, and trilineage differentiation assays. Optimal MB concentration (ranging from 101 to 108 MBs/mL) was screened via Cell Counting Kit-8 assay. Subsequently, UTMD exposure duration were optimized (60-600 seconds at 0.8 W/cm2, 2.4 MHz) by assessing cell proliferation and migration. Under optimal conditions, CXCR4 expression (quantitative real-time polymerase chain reaction, western blot, immunofluorescence), apoptosis (flow cytometry), and transcriptome changes (RNA sequencing) were assessed.
RESULTS
The SF6 MBs have a uniform size (1010 ± 178 nm) and a zeta potential of -13.5 mV. An MB concentration of 1 × 107 MBs/mL was determined to be the optimal level, showing no significant cytotoxicity. UTMD acted time-dependently on hUCMSCs. UTMD300s performed the best in cell proliferation (> 30%, P < 0.001) and migration (P < 0.05). Exposure > 300 s impaired cell viability and migration. Optimized UTMD upregulated CXCR4 expression in hUCMSCs (P < 0.05). Apoptosis assays verified the biosafety of UTMD300s. RNA sequencing revealed 159 differentially expressed genes (83 upregulated, 76 downregulated). These differentially expressed genes were mainly enriched in unsaturated fatty acid biosynthesis, 5-hydroxytryptamine receptor binding, and phospholipid metabolism pathways, with hub genes including SCD, INSIG1, HMGCS1, and ABCG1.
CONCLUSION
When UTMD300s is combined with MBs 107/mL, it can promote hUCMSC proliferation, migration, and significantly upregulate the expression of CXCR4 at both transcriptional and protein levels.
Core Tip: Enhancing the migratory capacity of transplanted human umbilical cord mesenchymal stem cells (hUCMSCs) remains a critical challenge in regenerative medicine. Ultrasound-targeted microbubble destruction (UTMD) is a promising non-invasive physical intervention, yet its optimal parameters and underlying mechanisms for promoting hUCMSC migration require further elucidation. Here, we introduce that when the microbubbles concentration is 1 × 107 particles/mL and the ultrasound exposure time is 300 seconds, UTMD technology can promote cell proliferation, migration by upregulating the expression levels of the C-X-C chemokine receptor type 4 gene and protein in hUCMSCs.
