2. Academic Validation
  3. Enhanced engraftment and immunomodulatory effects of integrin alpha-2-overexpressing mesenchymal stromal cells in lipopolysaccharide-induced acute lung injury

Enhanced engraftment and immunomodulatory effects of integrin alpha-2-overexpressing mesenchymal stromal cells in lipopolysaccharide-induced acute lung injury

  • Stem Cell Res Ther. 2025 Jun 3;16(1):286. doi: 10.1186/s13287-025-04423-1.
Hana Kang 1,  Ok-Hyeon Kim 2,  Eun Seo Chang 1,  Jinho Kim 3,  Ji-Young Kim 3,  Geun-Seup Shin 3,  Chul-Hong Kim 3,  Younghyun Lim 3,  Young-Jin Seo 3,  Jung-Woong Kim 4,  Hyun Jung Lee 5 6
Affiliations

Affiliations

  • 1 Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, 06974, South Korea.
  • 2 Department of Anatomy and Cell Biology, College of Medicine, Chung-Ang University, Seoul, 06974, South Korea.
  • 3 Department of Life Science, Chung-Ang University, Seoul, 06974, South Korea.
  • 4 Department of Life Science, Chung-Ang University, Seoul, 06974, South Korea. jungkim@cau.ac.kr.
  • 5 Department of Global Innovative Drugs, Graduate School of Chung-Ang University, Seoul, 06974, South Korea. pluto38@cau.ac.kr.
  • 6 Department of Anatomy and Cell Biology, College of Medicine, Chung-Ang University, Seoul, 06974, South Korea. pluto38@cau.ac.kr.
PMID: 40462215 DOI: 10.1186/s13287-025-04423-1
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.

Keywords

Acute lung injury (ALI); Cell therapy; Immunomodulation; Integrin alpha 2 (ITGA2); Mesenchymal stromal cells (MSCs).

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