What question did this study set out to answer?

To explore the role of CXCL10 signaling in modulating the immunoregulatory functions of mesenchymal stem cells.

May 24, 2026Open Access

CXCL10-LACTC1/C2 Expressing Mesenchymal Stem Cell Conditioned Medium Attenuates TNF-α-Induced Gene Expressions and Cell Viability in HUVECs

Key Points

To explore the role of CXCL10 signaling in modulating the immunoregulatory functions of mesenchymal stem cells.
Genetically engineered Wharton's jelly-derived MSCs to express CXCL10-LACTC1/C2 fusion protein.
Analyzed the conditioned medium impact on TNF-α-induced inflammatory responses in HUVECs.
Assessed expression of immunoregulatory mediators and endothelial activation markers.
Conditioned medium from CXCL10-LACTC1/C2-MSCs significantly reduced TNF-α-induced inflammatory marker expression in HUVECs (e.g., ICAM-1, PECAM-1).
Increased cell viability in HUVECs exposed to the MSC-derived conditioned medium as compared to controls.
Elevated expression levels of IDO1, TGF-β1, and IL4I1 in CXCL10-LACTC1/C2-expressing MSCs were observed.

Abstract

Infectious diseases exacerbate atherosclerosis-associated morbidity and mortality by inducing sustained inflammatory responses characterized by elevated IL-6, TNF-α, IFN-γ, and CXCL10. Persistent CXCL10-driven recruitment of CXCR3⁺ immune cells promotes endothelial dysfunction and atherosclerotic progression. Although mesenchymal stem cells (MSCs) respond to inflammatory cues and secrete CXCL10, the contribution of CXCL10/CXCR3 signaling to intrinsic MSC immunomodulatory programming remains poorly understood. The objective of this study is to investigate whether CXCL10 signaling can modulate MSC-mediated immunoregulation. To address this, Wharton's jelly-derived MSCs (WJ-MSCs) were genetically engineered to express a membrane-anchored CXCL10-Lactadherin C1/C2 fusion protein (CXCL10-LACTC1/C2). This strategy was designed to recapitulate physiological, localized, and sustained CXCL10 signaling, enabling spatially restricted chemokine presentation that more closely mimics cell-associated CXCL10 in inflammatory microenvironments compared with soluble CXCL10. The Lactadherin C1/C2 domain was selected to achieve stable, physiological membrane anchoring without introducing artificial transmembrane domains or compromising CXCL10 bioactivity. CXCL10-LACTC1/C2-expressing MSCs exhibited increased expression of key immunoregulatory mediators, including IDO1, TGF-β1, and IL4I1. Furthermore, conditioned medium derived from these MSCs attenuated TNF-α-induced inflammatory responses in human umbilical vein endothelial cells (HUVECs), as indicated by the modulation of endothelial activation and homeostasis markers (ICAM-1, PECAM-1, KDR, vWF, and NRF2) and improvement of cell viability. Collectively, these findings provide mechanistic insight into CXCL10-mediated MSC immunoregulation and support further investigation of MSC-based and cell-free therapeutic strategies aimed at mitigating CXCL10-driven endothelial inflammation in infection-associated vascular injury and atherosclerotic disease progression.

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