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Allogeneic Human Mesenchymal Stem Cells Restore Epithelial Protein Permeability in Cultured Human Alveolar Type II Cells by Secretion of Angiopoietin-1*
Open accessAbstract
Acute lung injury is characterized by injury to the lung epithelium that leads to impaired resolution of pulmonary edema and also facilitates accumulation of protein-rich edema fluid and inflammatory cells in the distal airspaces of the lung. Recent in vivo and in vitro studies suggest that mesenchymal stem cells (MSC) may have therapeutic value for the treatment of acute lung injury. Here we tested the ability of human allogeneic mesenchymal stem cells to restore epithelial permeability to protein across primary cultures of polarized human alveolar epithelial type II cells after an inflammatory insult. Alveolar epithelial type II cells were grown on a Transwell plate with an air-liquid interface and injured by cytomix, a combination of IL-1beta, TNFalpha, and IFNgamma. Protein permeability measured by (131)I-labeled albumin flux was increased by 5-fold over 24 h after cytokine-induced injury. Co-culture of human MSC restored type II cell epithelial permeability to protein to control levels. Using siRNA knockdown of potential paracrine soluble factors, we found that angiopoietin-1 secretion was responsible for this beneficial effect in part by preventing actin stress fiber formation and claudin 18 disorganization through suppression of NFkappaB activity. This study provides novel evidence for a beneficial effect of MSC on alveolar epithelial permeability to protein.
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“Such upregulation may have important clinical implications since VEGF and Ang-1 have been shown to play pivotal roles in angiogenesis, alveolar development, and treatment of acute lung injury (ALI) [8, 57–60].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [8]
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Metadata
- Authors
- Fang, X., Neyrinck, A. P., Matthay, M. A., & Lee, J. W.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Lee, Jae W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 285
- Issue
- 34
- Pages
- 26211-26222
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2924032
- OpenAlex
- W2044217893
- Cited by
- 258
- References
- 55
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 9 · 2022: 19 · 2021: 28 · 2020: 19 · 2019: 15 · 2018: 19 · 2017: 18 · 2016: 17 · 2015: 16 · 2014: 25 · 2013: 17 · 2012: 25
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- University of Pittsburgh
- National Institutes of Health (HL51856)
- National Heart, Lung, and Blood Institute (093026, HL51854, K08HL093026, HL-51856, R01HL051856, HL-093026, 51856, R01HL051854, R37HL051856)
- National Center for Research Resources (P40RR017447)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- allogeneic mesenchymal stem cells, angiopoietin-1, alveolar type II cells, acute lung injury, paracrine signaling, stress fibers, claudin-18, NF-κB, pulmonary edema
- MeSH terms
- Cells, Cultured, Epithelium, Humans, Models, Biological, Permeability, Pulmonary Alveoli, Cytokines, Coculture Techniques, Protein Transport, Angiopoietin-1, Acute Lung Injury, Mesenchymal Stem Cells
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