Enhanced engraftment and immunomodulatory effects of integrin alpha-2-overexpressing mesenchymal stromal cells in lipopolysaccharide-induced acute lung injury
Abstract Background Human mesenchymal stromal cells (MSCs) have potential as a treatment for inflammatory diseases, including acute lung injury (ALI), due to their anti-inflammatory and immunomodulatory properties. However, their clinical efficacy is often limited by poor post-transplant survival an...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-06-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13287-025-04423-1 |
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| Summary: | Abstract Background Human mesenchymal stromal cells (MSCs) have potential as a treatment for inflammatory diseases, including acute lung injury (ALI), due to their anti-inflammatory and immunomodulatory properties. However, their clinical efficacy is often limited by poor post-transplant survival and adaptability in the host environment. Accordingly, MSCs are primed to boost their therapeutic efficacy for treating a variety of diseases. In our previous study, we discovered that culturing MSCs in a functional polymer-based 3D niche, which simulates the in vivo microenvironment, significantly increased integrin alpha 2 (ITGA2) expression compared to traditional 2D cultures, as revealed by RNA-seq analysis. Methods ITGA2 was used to prime MSCs and their therapeutic potential evaluated in ALI models. Human bone marrow-derived MSCs were transfected with mEmerald-ITGA2 vectors and intravenously injected at 6 h post-ALI induction. Histological and biochemical analyses explored the therapeutic effects and molecular mechanisms of ITGA2-MSCs (ITGA2 overexpressing MSCs) in lipopolysaccharide (LPS)-induced ALI models. Results ITGA2-MSCs effectively ameliorated lung tissue injury and lowered blood IL-6 levels compared to that of the control group. Additionally, CD206 expression was highest in the ITGA2-MSC group, which was associated with the activation of M2 macrophage polarization, which contributed to inflammation reduction and tissue repair. Finally, ITGA2-MSCs demonstrated enhanced survival and adaptability when intravenously administered to mice, as indicated by the in vivo imaging system (IVIS). Conclusions ITGA2 creates a favorable microenvironment for MSCs, enhancing their immunomodulatory functions, ultimately offering a promising strategy for MSC-based cell therapy for ALI. |
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| ISSN: | 1757-6512 |