Evaluating the Dose-Dependent Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Preclinical Model of Interstitial Lung Disease.
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| Titel: | Evaluating the Dose-Dependent Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Preclinical Model of Interstitial Lung Disease. |
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| Autoren: | Kotani T; Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Osaka, Japan., Saito T; Department of Legal Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Osaka, Japan.; Laboratory of Microbial Informatics, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki 567-0085, Osaka, Japan., Masutani R; Division of Central Laboratory, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Osaka, Japan., Uemura S; School of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Osaka, Japan., Matsuda S; Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Osaka, Japan., Suzuka T; Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Osaka, Japan., Ikemoto M; Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Osaka, Japan., Takeuchi T; Department of Internal Medicine (IV), Division of Rheumatology, Osaka Medical and Pharmaceutical University, Takatsuki 569-8686, Osaka, Japan. |
| Quelle: | International journal of molecular sciences [Int J Mol Sci] 2025 Oct 15; Vol. 26 (20). Date of Electronic Publication: 2025 Oct 15. |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, [2000- |
| MeSH-Schlagworte: | Mesenchymal Stem Cells*/cytology , Mesenchymal Stem Cells*/metabolism , Mesenchymal Stem Cell Transplantation*/methods , Umbilical Cord*/cytology , Lung Diseases, Interstitial*/therapy , Lung Diseases, Interstitial*/pathology , Lung Diseases, Interstitial*/chemically induced , Lung Diseases, Interstitial*/metabolism, Animals ; Humans ; Mice ; Female ; Disease Models, Animal ; Mice, Inbred C57BL ; Bleomycin ; Matrix Metalloproteinase 9/metabolism ; Pulmonary Fibrosis/therapy ; Pulmonary Fibrosis/pathology ; Cytokines/metabolism ; Macrophages/metabolism ; Tissue Inhibitor of Metalloproteinase-1/metabolism |
| Abstract: | Interstitial lung disease associated with connective tissue disease (CTD-ILD) is a severe condition characterized by inflammation and progressive lung fibrosis, with limited treatment options. Previous studies have demonstrated the anti-inflammatory and antifibrotic properties of human umbilical cord-derived mesenchymal stem cells (huMSCs), suggesting their potential as novel therapeutic agents. Therefore, we investigated the dose-dependent therapeutic effects of huMSCs on CTD-ILD. A bleomycin-induced mouse model of interstitial lung disease, in which female C57BL/6J mice developed diffuse pulmonary lesions following continuous subcutaneous infusion of bleomycin, was used. Mice subsequently received intravenous huMSCs at doses of 1.0 × 10 3 , 1.0 × 10 4 , or 1.0 × 10 5 cells. The medium dose (1.0 × 10 4 cells) showed the most pronounced effects on pulmonary fibrosis and collagen deposition, while significantly suppressing pro-inflammatory cytokines, including interleukin-1β and interleukin-6; however, this effect was not consistent across all measured outcomes. The treatment also enhanced beneficial matrix remodeling by downregulating TIMP-1 and upregulating MMP-9 expression. Furthermore, huMSC administration modulated macrophage polarization and inhibited the pro-inflammatory M1 phenotype. These findings highlight the therapeutic potential of huMSCs for CTD-ILD and underscore the importance of dose optimization to balance efficacy and safety. |
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| Contributed Indexing: | Keywords: MMP-9; TIMP-1; connective tissue disease; human umbilical cord-derived mesenchymal stem cell; interstitial lung disease |
| Substance Nomenclature: | 11056-06-7 (Bleomycin) EC 3.4.24.35 (Matrix Metalloproteinase 9) 0 (Cytokines) 0 (Tissue Inhibitor of Metalloproteinase-1) |
| Entry Date(s): | Date Created: 20251029 Date Completed: 20251029 Latest Revision: 20251101 |
| Update Code: | 20251101 |
| PubMed Central ID: | PMC12564416 |
| DOI: | 10.3390/ijms262010016 |
| PMID: | 41155309 |
| Datenbank: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstract: | Interstitial lung disease associated with connective tissue disease (CTD-ILD) is a severe condition characterized by inflammation and progressive lung fibrosis, with limited treatment options. Previous studies have demonstrated the anti-inflammatory and antifibrotic properties of human umbilical cord-derived mesenchymal stem cells (huMSCs), suggesting their potential as novel therapeutic agents. Therefore, we investigated the dose-dependent therapeutic effects of huMSCs on CTD-ILD. A bleomycin-induced mouse model of interstitial lung disease, in which female C57BL/6J mice developed diffuse pulmonary lesions following continuous subcutaneous infusion of bleomycin, was used. Mice subsequently received intravenous huMSCs at doses of 1.0 × 10 <sup>3</sup> , 1.0 × 10 <sup>4</sup> , or 1.0 × 10 <sup>5</sup> cells. The medium dose (1.0 × 10 <sup>4</sup> cells) showed the most pronounced effects on pulmonary fibrosis and collagen deposition, while significantly suppressing pro-inflammatory cytokines, including interleukin-1β and interleukin-6; however, this effect was not consistent across all measured outcomes. The treatment also enhanced beneficial matrix remodeling by downregulating TIMP-1 and upregulating MMP-9 expression. Furthermore, huMSC administration modulated macrophage polarization and inhibited the pro-inflammatory M1 phenotype. These findings highlight the therapeutic potential of huMSCs for CTD-ILD and underscore the importance of dose optimization to balance efficacy and safety. |
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| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms262010016 |