Human umbilical cord mesenchymal stem cell-derived extracellular vesicles ameliorate airway inflammation in a rat model of chronic obstructive pulmonary disease (COPD).

Autor: Ridzuan N; Lung Stem Cell and Gene Therapy Group, Regenerative Medicine Cluster, Advanced Medical and Dental Institute (IPPT), SAINS@BERTAM, Universiti Sains Malaysia, 13200, Bertam, Penang, Malaysia., Zakaria N; Lung Stem Cell and Gene Therapy Group, Regenerative Medicine Cluster, Advanced Medical and Dental Institute (IPPT), SAINS@BERTAM, Universiti Sains Malaysia, 13200, Bertam, Penang, Malaysia., Widera D; Stem Cell Biology and Regenerative Medicine, School of Pharmacy, University of Reading, Reading, RG6 6AP, UK., Sheard J; Stem Cell Biology and Regenerative Medicine, School of Pharmacy, University of Reading, Reading, RG6 6AP, UK., Morimoto M; RIKEN Centre for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuou-ku, Kobe, 650-0047, Japan., Kiyokawa H; RIKEN Centre for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuou-ku, Kobe, 650-0047, Japan., Mohd Isa SA; Department of Pathology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150, Kubang Kerian, Malaysia., Chatar Singh GK; Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia., Then KY; CryoCord Sdn Bhd, Bio-X Centre, 63000, Cyberjaya, Selangor, Malaysia., Ooi GC; CryoCord Sdn Bhd, Bio-X Centre, 63000, Cyberjaya, Selangor, Malaysia., Yahaya BH; Lung Stem Cell and Gene Therapy Group, Regenerative Medicine Cluster, Advanced Medical and Dental Institute (IPPT), SAINS@BERTAM, Universiti Sains Malaysia, 13200, Bertam, Penang, Malaysia. badrul@usm.my.; USM-RIKEN International Centre for Ageing Science (URICAS), Universiti Sains Malaysia, 11800, Gelugor, Penang, Malaysia. badrul@usm.my.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2021 Jan 12; Vol. 12 (1), pp. 54. Date of Electronic Publication: 2021 Jan 12.
DOI: 10.1186/s13287-020-02088-6
Abstrakt: Background: Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin.
Methods: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student's t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD).
Results: Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD.
Conclusions: In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.
Databáze: MEDLINE
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