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Identification and modulation of microenvironment is crucial for effective mesenchymal stromal cell therapy in acute lung injury
- Source :
- American Journal of Respiratory and Critical Care Medicine
- Publication Year :
- 2019
-
Abstract
- Rationale: There are controversial reports on applications of mesenchymal stromal cells (MSCs) in patients with acute respiratory distress syndrome (ARDS). Objectives: We hypothesized that lung microenvironment was the main determinant of beneficial versus detrimental effects of MSCs during ARDS. Methods: Lung proteome was profiled in three models of injury induced by acid instillation and/or mechanical ventilation in mice. Human gene of glutathione peroxidase-1 was delivered before MSC administration; or MSCs carrying human gene of IL-10 or hepatocyte growth factor were administered after lung injury. An inhibitory cocktail against IL-6, fibronectin, and oxidative stress was used in in vitro studies using human small airway epithelial cells and human MSCs after exposure to plasma of patients with ARDS. Measurements and Main Results: Distinct proteomic profiles were observed in three lung injury models. Administration of MSCs protected lung from ventilator-induced injury, whereas it worsened acid-primed lung injuries associated with fibrotic development in lung environment that had high levels of IL-6 and fibronectin along with low antioxidant capacity. Correction of microenvironment with glutathione peroxidase-1, or treatment with MSCs carrying human gene of IL-10 or hepatocyte growth factor after acid-primed injury, reversed the detrimental effects of native MSCs. Proteomic profiles obtained in the mouse models were also similarly observed in human ARDS. Treatment with the inhibitory cocktail in samples of patients with ARDS retained protective effects of MSCs in small airway epithelial cells. Conclusions: MSCs can be beneficial or detrimental depending on microenvironment at the time of administration. Identification of potential beneficiaries seems to be crucial to guide MSC therapy in ARDS.
- Subjects :
- Pulmonary and Respiratory Medicine
Adult
Proteomics
ARDS
Stromal cell
Proteome
Cell- and Tissue-Based Therapy
Lung injury
Critical Care and Intensive Care Medicine
Mesenchymal Stem Cell Transplantation
Cell therapy
03 medical and health sciences
Mice
0302 clinical medicine
Fibrosis
medicine
Animals
Humans
030212 general & internal medicine
Respiratory Distress Syndrome
Lung
Acute respiratory distress syndrome
business.industry
Animal
Mesenchymal stem cell
Editorials
medicine.disease
Disease Models, Animal
medicine.anatomical_structure
Respiratory Distress Syndrome, Adult
030228 respiratory system
Disease Models
Cancer research
Hepatocyte growth factor
business
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory and Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....293ff9f42116cc5ed41b1d2a3a99c9a8