Melanoma cell adhesion molecule-positive mesenchymal stromal cells alleviate acute respiratory distress syndrome via nuclear factor kappa-B-mediated paracrine regulation
Year: 2025
Type: article
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.
Source: World Journal of Stem Cells
Authors: Ya-Li Zhang, Ding-Ke Wen, Sheng-Nan Wang, Yi Tan, He-Ran Ma
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4415854939