Melanoma cell adhesion molecule-positive mesenchymal stromal cells alleviate acute respiratory distress syndrome via nuclear factor kappa-B-mediated paracrine regulation

doi:10.4252/wjsc.v17.i10.109284

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Oct 26, 2025 (publication date) through Oct 28, 2025

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World Journal of Stem Cells

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1948-0210

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Stem Cells. Oct 26, 2025; 17(10): 109284
Published online Oct 26, 2025. doi: 10.4252/wjsc.v17.i10.109284

Melanoma cell adhesion molecule-positive mesenchymal stromal cells alleviate acute respiratory distress syndrome via nuclear factor kappa-B-mediated paracrine regulation

Ya-Li Zhang, Ding-Ke Wen, Sheng-Nan Wang, Yi Tan, He-Ran Ma

Ya-Li Zhang, Ding-Ke Wen, Sheng-Nan Wang, Yi Tan, He-Ran Ma, Department of Research and Development, Qilu Cell Therapy Technology Co., Ltd, Jinan 250000, Shandong Province, China

Co-corresponding authors: Yi Tan and He-Ran Ma.

Author contributions: Tan Y and Ma HR conceived of and designed the study, supervised the research, and revised the manuscript critically for intellectual content; they contributed equally to this manuscript and are co-corresponding authors; Zhang YL designed the experiments; Zhang YL, Wen DK, and Wang SN performed the experiments; Zhang YL and Wang SN analyzed the data; Zhang YL drafted the manuscript. All authors read and approved the final manuscript.

Supported by the Science and Technology SMEs Innovation Capacity Improvement Project of Shandong Province, No. 2022TSGC1004; and National Key R&D Program of China, No. 2021YFA1101502.

Institutional review board statement: The source, screening, and collection process of human umbilical cords at Yantai Yuhuangding Hospital Affiliated with Qingdao University met the national ethical requirements, and the ethical approval number was[2021]003.

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 Experimental Animal Ethics Committee of Army Medical University approved the experiments, and the ethical approval number was No. AMUWEC20210830.

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: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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: He-Ran Ma, PhD, Department of Research and Development, Qilu Cell Therapy Technology Co., Ltd, No. 6 Gangyuan Road, Licheng District, Jinan 250000, Shandong Province, China. maheran@yinfeng.com.cn

Received: May 8, 2025
Revised: June 24, 2025
Accepted: August 27, 2025
Published online: October 26, 2025
Processing time: 171 Days and 16 Hours

Abstract

BACKGROUND

Mesenchymal stromal cells (MSCs) are renowned for their immunosuppressive properties, which make them widely used in managing excessive inflammation. Although CD146+ and CD146- MSCs exhibit similar morphological traits and surface marker expression levels, the specific characteristics and differential regulatory mechanisms of these two subtypes remain poorly understood. This knowledge gap has limited the precise application of MSCs in targeted therapeutic strategies.

AIM

To compare the functional differences between CD146+ and CD146- MSCs and investigate the underlying mechanisms.

METHODS

In this study, magnetic beads were used to sort umbilical cord-derived MSCs into CD146+ and CD146- subsets. The pro-angiogenic factors (hepatocyte growth factor, prostaglandin E2, vascular endothelial growth factor, angiopoietin-1) production and immunomodulatory effects on T lymphocyte subsets were evaluated in vitro. The therapeutic efficacy was assessed in an acute respiratory distress syndrome (ARDS) mouse model via tail vein injection.

RESULTS

Cytokine secretion and angiogenesis: CD146+ MSCs significantly increased the production of hepatocyte growth factor, prostaglandin E2, vascular endothelial growth factor, and angiopoietin-1 and exhibited increased pro-angiogenic activity in vitro. Immunomodulatory effects: CD146+ MSCs potently inhibited the differentiation and proliferation of pro-inflammatory T helper type 1/T helper type 17 cells while promoting the expansion of regulatory T cells during T lymphocyte activation. ARDS therapy: In a mouse ARDS model, compared with CD146- MSCs, CD146+ MSCs demonstrated superior therapeutic efficacy, as evidenced by improved clinical scores. Mechanistically, CD146+ MSCs activated the nuclear factor kappa B pathway, upregulated cyclooxygenase 2 expression, and facilitated damaged epithelial cell repair.

CONCLUSION

CD146+ MSCs show stronger ARDS therapeutic potential than CD146- MSCs via pro-angiogenic/immunomodulatory traits. Nuclear factor kappa B/cyclooxygenase 2 activation aids epithelial repair, highlighting CD146+ MSCs as promising targets.

Keywords: Mesenchymal stromal cells; Melanoma cell adhesion molecule; Acute respiratory distress syndrome; Nuclear factor kappa B; CD146

Core Tip: Mesenchymal stromal cells (MSCs) are recognized for their immunosuppressive properties and are widely used to control excessive inflammation. This study demonstrated that, compared with CD146- MSCs, CD146+ MSCs exhibit greater secretion of pro-angiogenic factors and enhanced anti-inflammatory and immunomodulatory capacities. CD146+ MSCs repair epithelial cells by activating the nuclear factor kappa B/cyclooxygenase 2 pathway, thereby exerting superior therapeutic efficacy in the treatment of acute respiratory distress syndrome.