Paracrine Regulation of Alveolar Epithelial Damage and Repair Responses by Human Lung-Resident Mesenchymal Stromal Cells

Autor: Mehmet Nizamoglu, Marnix R. Jonker, Harold G. de Bruin, Simon D. Pouwels, Dennis M L W Kruk, Karla F. Arevalo Gomez, Marissa Wisman, Jacobien A. Noordhoek, Nick H. T. ten Hacken, Irene H. Heijink
Přispěvatelé: Groningen Research Institute for Asthma and COPD (GRIAC)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Necrosis
MSCs
ACTIVATION
Cell therapy
Pulmonary Disease
Chronic Obstructive
Cell Movement
Transforming Growth Factor beta
lung repair
Medicine
Biology (General)
organoids
Cell Death
General Medicine
Middle Aged
respiratory system
medicine.anatomical_structure
emphysema
Female
medicine.symptom
STEM-CELLS
GROWTH-FACTOR
QH301-705.5
Alveolar Epithelium
alveolar epithelium
regenerative medicine
Models
Biological
Article
Epithelial Damage
Paracrine signalling
Cell Line
Tumor
Spheroids
Cellular
Paracrine Communication
growth factors
Organoid
Humans
Regeneration
COPD
RNA
Messenger
Aged
Cell Proliferation
Lung
TRANSPLANTATION
business.industry
Mesenchymal stem cell
Mesenchymal Stem Cells
respiratory tract diseases
Oxidative Stress
Alveolar Epithelial Cells
Culture Media
Conditioned
Cancer research
cell therapy
business
Zdroj: Cells
Volume 10
Issue 11
Cells, 10(11):2860. MDPI AG
Cells, Vol 10, Iss 2860, p 2860 (2021)
ISSN: 2073-4409
DOI: 10.3390/cells10112860
Popis: COPD is characterized by irreversible lung tissue damage. We hypothesized that lung-derived mesenchymal stromal cells (LMSCs) reduce alveolar epithelial damage via paracrine processes, and may thus be suitable for cell-based strategies in COPD. We aimed to assess whether COPD-derived LMSCs display abnormalities. LMSCs were isolated from lung tissue of severe COPD patients and non-COPD controls. Effects of LMSC conditioned-medium (CM) on H2O2-induced, electric field- and scratch-injury were studied in A549 and NCI-H441 epithelial cells. In organoid models, LMSCs were co-cultured with NCI-H441 or primary lung cells. Organoid number, size and expression of alveolar type II markers were assessed. Pre-treatment with LMSC-CM significantly attenuated oxidative stress-induced necrosis and accelerated wound repair in A549. Co-culture with LMSCs supported organoid formation in NCI-H441 and primary epithelial cells, resulting in significantly larger organoids with lower type II-marker positivity in the presence of COPD-derived versus control LMSCs. Similar abnormalities developed in organoids from COPD compared to control-derived lung cells, with significantly larger organoids. Collectively, this indicates that LMSCs’ secretome attenuates alveolar epithelial injury and supports epithelial repair. Additionally, LMSCs promote generation of alveolar organoids, with abnormalities in the supportive effects of COPD-derived LMCS, reflective of impaired regenerative responses of COPD distal lung cells.
Databáze: OpenAIRE
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