Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein
Abstract Severe COVID-19 is characterized by thrombo-inflammatory processes within the lung microvasculature. In pursuit of effective treatments, clinical studies explored mesenchymal stromal cells (MSCs) as a promising approach due to their anti-inflammatory, immunomodulatory, and regenerative prop...
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BMC
2025-07-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04472-6 |
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| author | Anna Pezzotta Alessandra Bovio Barbara Imberti Monica Locatelli Daniela Corna Domenico Cerullo Sara Gastoldi Ariela Benigni Giuseppe Remuzzi Marina Morigi Luca Perico |
| author_facet | Anna Pezzotta Alessandra Bovio Barbara Imberti Monica Locatelli Daniela Corna Domenico Cerullo Sara Gastoldi Ariela Benigni Giuseppe Remuzzi Marina Morigi Luca Perico |
| author_sort | Anna Pezzotta |
| collection | DOAJ |
| description | Abstract Severe COVID-19 is characterized by thrombo-inflammatory processes within the lung microvasculature. In pursuit of effective treatments, clinical studies explored mesenchymal stromal cells (MSCs) as a promising approach due to their anti-inflammatory, immunomodulatory, and regenerative properties, through their paracrine action. Here, we tested the conditioned medium (CM) derived from human umbilical cord (UC)-MSCs in acute lung injury induced by the spike protein subunit 1 (S1) in ACE2-humanized male mice. Injection of CM significantly limited S1-induced lung injury, edema, and fibrosis. This was associated with reduced vascular dysfunction, in terms of restored thrombomodulin levels and decreased von Willebrand (vWF) expression. By preserving endothelial glycocalyx, CM reduced complement C3 accumulation, favoring factor H binding on the lung microvasculature. Reduced oxidative stress, nuclear NF-κB p65 accumulation, and inflammatory cell infiltration were also observed in response to CM in S1-injected mice. In vitro, CM counteracted thrombo-inflammation by preserving thrombomodulin, as well as limiting vWF expression, due to endothelial glycocalyx recovery. CM reduced nuclear translocation of NF-κB p65 and its downstream targets, ICAM-1 and P-selectin, translating in decreased C3 deposits, platelet aggregation, and leukocyte adhesion on S1-challenged endothelial cells. Collectively, these data indicate that UC-MSC-derived secretome represents a promising therapy in COVID-19 due to its potent anti-thrombotic and anti-inflammatory effects on lung microcirculation. |
| format | Article |
| id | doaj-art-ad7fa06c07eb4a7eaccfcc634d0584e7 |
| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-ad7fa06c07eb4a7eaccfcc634d0584e72025-08-20T03:37:20ZengBMCStem Cell Research & Therapy1757-65122025-07-0116112010.1186/s13287-025-04472-6Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike proteinAnna Pezzotta0Alessandra Bovio1Barbara Imberti2Monica Locatelli3Daniela Corna4Domenico Cerullo5Sara Gastoldi6Ariela Benigni7Giuseppe Remuzzi8Marina Morigi9Luca Perico10Department of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSDepartment of Molecular Medicine, Istituto di Ricerche Farmacologiche Mario Negri IRCCSAbstract Severe COVID-19 is characterized by thrombo-inflammatory processes within the lung microvasculature. In pursuit of effective treatments, clinical studies explored mesenchymal stromal cells (MSCs) as a promising approach due to their anti-inflammatory, immunomodulatory, and regenerative properties, through their paracrine action. Here, we tested the conditioned medium (CM) derived from human umbilical cord (UC)-MSCs in acute lung injury induced by the spike protein subunit 1 (S1) in ACE2-humanized male mice. Injection of CM significantly limited S1-induced lung injury, edema, and fibrosis. This was associated with reduced vascular dysfunction, in terms of restored thrombomodulin levels and decreased von Willebrand (vWF) expression. By preserving endothelial glycocalyx, CM reduced complement C3 accumulation, favoring factor H binding on the lung microvasculature. Reduced oxidative stress, nuclear NF-κB p65 accumulation, and inflammatory cell infiltration were also observed in response to CM in S1-injected mice. In vitro, CM counteracted thrombo-inflammation by preserving thrombomodulin, as well as limiting vWF expression, due to endothelial glycocalyx recovery. CM reduced nuclear translocation of NF-κB p65 and its downstream targets, ICAM-1 and P-selectin, translating in decreased C3 deposits, platelet aggregation, and leukocyte adhesion on S1-challenged endothelial cells. Collectively, these data indicate that UC-MSC-derived secretome represents a promising therapy in COVID-19 due to its potent anti-thrombotic and anti-inflammatory effects on lung microcirculation.https://doi.org/10.1186/s13287-025-04472-6COVID-19Spike protein 1ComplementEndothelial dysfunctionGlycocalyxThrombo-inflammation |
| spellingShingle | Anna Pezzotta Alessandra Bovio Barbara Imberti Monica Locatelli Daniela Corna Domenico Cerullo Sara Gastoldi Ariela Benigni Giuseppe Remuzzi Marina Morigi Luca Perico Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein Stem Cell Research & Therapy COVID-19 Spike protein 1 Complement Endothelial dysfunction Glycocalyx Thrombo-inflammation |
| title | Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein |
| title_full | Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein |
| title_fullStr | Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein |
| title_full_unstemmed | Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein |
| title_short | Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein |
| title_sort | mesenchymal stromal cell secretome reduces lung injury and thrombo inflammation induced by sars cov 2 spike protein |
| topic | COVID-19 Spike protein 1 Complement Endothelial dysfunction Glycocalyx Thrombo-inflammation |
| url | https://doi.org/10.1186/s13287-025-04472-6 |
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