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Intratracheal transplantation of trophoblast stem cells attenuates acute lung injury in mice
- Source :
- Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-14 (2021), Stem Cell Research & Therapy
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Background Acute lung injury (ALI) is a common lung disorder that affects millions of people every year. The infiltration of inflammatory cells into the lungs and death of the alveolar epithelial cells are key factors to trigger a pathological cascade. Trophoblast stem cells (TSCs) are immune privileged, and demonstrate the capability of self-renewal and multipotency with differentiation into three germ layers. We hypothesized that intratracheal transplantation of TSCs may alleviate ALI. Methods ALI was induced by intratracheal delivery of bleomycin (BLM) in mice. After exposure to BLM, pre-labeled TSCs or fibroblasts (FBs) were intratracheally administered into the lungs. Analyses of the lungs were performed for inflammatory infiltrates, cell apoptosis, and engraftment of TSCs. Pro-inflammatory cytokines/chemokines of lung tissue and in bronchoalveolar lavage fluid (BALF) were also assessed. Results The lungs displayed a reduction in cellularity, with decreased CD45+ cells, and less thickening of the alveolar walls in ALI mice that received TSCs compared with ALI mice receiving PBS or FBs. TSCs decreased infiltration of neutrophils and macrophages, and the expression of interleukin (IL) 6, monocyte chemoattractant protein-1 (MCP-1) and keratinocyte-derived chemokine (KC) in the injured lungs. The levels of inflammatory cytokines in BALF, particularly IL-6, were decreased in ALI mice receiving TSCs, compared to ALI mice that received PBS or FBs. TSCs also significantly reduced BLM-induced apoptosis of alveolar epithelial cells in vitro and in vivo. Transplanted TSCs integrated into the alveolar walls and expressed aquaporin 5 and prosurfactant protein C, markers for alveolar epithelial type I and II cells, respectively. Conclusion Intratracheal transplantation of TSCs into the lungs of mice after acute exposure to BLM reduced pulmonary inflammation and cell death. Furthermore, TSCs engrafted into the alveolar walls to form alveolar epithelial type I and II cells. These data support the use of TSCs for the treatment of ALI.
- Subjects :
- Lipopolysaccharides
Medicine (General)
Chemokine
Pathology
medicine.medical_specialty
Trophoblast stem cells
Medicine (miscellaneous)
Inflammation
QD415-436
Lung injury
Biochemistry
Biochemistry, Genetics and Molecular Biology (miscellaneous)
Proinflammatory cytokine
Mice
R5-920
Acute lung injury
medicine
Animals
Lung
biology
medicine.diagnostic_test
business.industry
Research
Stem Cells
Monocyte
Engraftment
Cell Biology
respiratory system
Trophoblasts
respiratory tract diseases
Mice, Inbred C57BL
Transplantation
Bronchoalveolar lavage
medicine.anatomical_structure
Alveolar epithelial cells
biology.protein
Molecular Medicine
medicine.symptom
Stem cell
business
Bronchoalveolar Lavage Fluid
Subjects
Details
- ISSN :
- 17576512
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Stem Cell Research & Therapy
- Accession number :
- edsair.doi.dedup.....2347990b6fdcaeacf109e30ab3f07fa1