Bone marrow-derived mesenchymal stem cells attenuate pulmonary inflammation and lung damage caused by highly pathogenic avian influenza A/H5N1 virus in BALB/c mice

Autor: Rima R. Prasetya, Yasuko Mori, Kazufumi Shimizu, Gatot Soegiarto, Yohko K. Shimizu, Soetjipto Koesnowidagdo, Fedik Abdul Rantam, Laksmi Wulandari, Maria Inge Lusida, Jezzy R. Dewantari, Aldise Mareta Nastri, Emmanuel Djoko Poetranto, Muhammad Amin, Resti Yudhawati
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Arterial blood gas analysis
BALB/c mouse
030106 microbiology
Lung injury
Mesenchymal Stem Cell Transplantation
Bone marrow-derived mesenchymal stem cells
Virus
lcsh:Infectious and parasitic diseases
BALB/c
Mice
03 medical and health sciences
Orthomyxoviridae Infections
Highly pathogenic avian influenza a/H5N1 virus
Acute lung injury
Animals
Cell-based therapy
Medicine
lcsh:RC109-216
Lung
Alveolar Cell Type I
Mice
Inbred BALB C
Alveolar cell regeneration
Influenza A Virus
H5N1 Subtype
Acute respiratory distress syndrome
biology
business.industry
Mesenchymal stem cell
Alveolar Cell Type II
Pneumonia
respiratory system
Inflammatory cytokines
biology.organism_classification
respiratory tract diseases
Disease Models
Animal
Treatment Outcome
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
Immunology
Cytokines
Bone marrow
business
Research Article
Zdroj: BMC Infectious Diseases, Vol 20, Iss 1, Pp 1-15 (2020)
BMC Infectious Diseases
ISSN: 1471-2334
Popis: Background The highly pathogenic avian influenza A/H5N1 virus is one of the causative agents of acute lung injury (ALI) with high mortality rate. Studies on therapeutic administration of bone marrow-derived mesenchymal stem cells (MSCs) in ALI caused by the viral infection have been limited in number and have shown conflicting results. The aim of the present investigation is to evaluate the therapeutic potential of MSC administration in A/H5N1-caused ALI, using a mouse model. Methods MSCs were prepared from the bone marrow of 9 to 12 week-old BALB/c mice. An H5N1 virus of A/turkey/East Java/Av154/2013 was intranasally inoculated into BALB/c mice. On days 2, 4, and 6 after virus inoculation, MSCs were intravenously administered into the mice. To evaluate effects of the treatment, we examined for lung alveolar protein as an indicator for lung injury, PaO2/FiO2 ratio for lung functioning, and lung histopathology. Expressions of NF-κB, RAGE (transmembrane receptor for damage associated molecular patterns), TNFα, IL-1β, Sftpc (alveolar cell type II marker), and Aqp5+ (alveolar cell type I marker) were examined by immunohistochemistry. In addition, body weight, virus growth in lung and brain, and duration of survival were measured. Results The administration of MSCs lowered the level of lung damage in the virus-infected mice, as shown by measuring lung alveolar protein, PaO2/FiO2 ratio, and histopathological score. In the MSC-treated group, the expressions of NF-κB, RAGE, TNFα, and IL-1β were significantly suppressed in comparison with a mock-treated group, while those of Sftpc and Aqp5+ were enhanced. Body weight, virus growth, and survival period were not significantly different between the groups. Conclusion The administration of MSCs prevented further lung injury and inflammation, and enhanced alveolar cell type II and I regeneration, while it did not significantly affect viral proliferation and mouse morbidity and mortality. The results suggested that MSC administration was a promissing strategy for treatment of acute lung injuries caused by the highly pathogenic avian influenza A/H5N1 virus, although further optimization and combination use of anti-viral drugs will be obviously required to achieve the goal of reducing mortality.
Databáze: OpenAIRE
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