Inhaled Placental Mesenchymal Stromal Cell Secretome from Two- and Three-Dimensional Cell Cultures Promotes Survival and Regeneration in Acute Lung Injury Model in Mice.

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is a common clinical problem, leading to significant morbidity and mortality, and no effective pharmacotherapy exists. The problem of ARDS causing mortality became more apparent during the COVID-19 pandemic. Biotherapeutic products containing multipotent mesenchymal stromal cell (MMSC) secretome may provide a new therapeutic paradigm for human healthcare due to their immunomodulating and regenerative abilities. The content and regenerative capacity of the secretome depends on cell origin and type of cultivation (two- or three-dimensional (2D/3D)). In this study, we investigated the proteomic profile of the secretome from 2D- and 3D-cultured placental MMSC and lung fibroblasts (LFBs) and the effect of inhalation of freeze-dried secretome on survival, lung inflammation, lung tissue regeneration, fibrin deposition in a lethal ALI model in mice. We found that three inhaled administrations of freeze-dried secretome from 2D- and 3D-cultured placental MMSC and LFB protected mice from death, restored the histological structure of damaged lungs, and decreased fibrin deposition. At the same time, 3D MMSC secretome exhibited a more pronounced trend in lung recovery than 2D MMSC and LFB-derived secretome in some measures. Taking together, these studies show that inhalation of cell secretome may also be considered as a potential therapy for the management of ARDS in patients suffering from severe pneumonia, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), however, their effectiveness requires further investigation.

• Authors: Vasily A Kudinov, Rafael I Artyushev, Irina M Zurina, Elena S Zorina, Roman D Lapshin, Ludmila B Snopova, Irina V Mukhina, Irina N Saburina
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 7 (Mar 22 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35408778 (Publication Type: Journal Article)

Chemical References

• Fibrin

Topics

• Acute Lung Injury (therapy)
• Animals
• COVID-19 (therapy)
• Cell Culture Techniques
• Female
• Fibrin
• Humans
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells
• Mice
• Pandemics
• Placenta
• Pneumonia
• Pregnancy
• Proteomics
• Respiratory Distress Syndrome (therapy)
• SARS-CoV-2
• Secretome