Management of Airway Remodeling in a Mouse Model of Allergic Airways Inflammation Using Extracellular Vesicles from Human Bone Marrow-Derived Mesenchymal Stromal Cells

Felipe Yukio Ishikawa Fragoso, Pedro Vicente Michelotto, Addeli Bez Batti Angulski, Lidiane Maria Boldrini Leite, Alexandra Cristina Senegaglia, Márcia Olandoski, Alejandro Correa Dominguez, Paulo Roberto Slud Brofman

Research output: Contribution to journalArticlepeer-review

Abstract

Asthma is a chronic respiratory disease affecting 300 million people worldwide. It results in several structural changes in the airways, which are minimally accessible in clinical practice. Cell therapy using mesenchymal stromal cells (MSCs) is a promising strategy for treating asthma due to the paracrine activity of MSCs, which influences tissue regeneration and modulates the immune response. Studies using extracellular vesicles (EV) released by MSCs have demonstrated their regenerative properties in animal models. The aim of this study was to evaluate the potential of EVs isolated from human bone marrow MSCs (hBM-MSCs) to control lung tissue remodeling in ovalbumin-induced allergic asthma in Balb/c mice. We isolated hBM-MSCs from a single donor, expanded and characterized them, and then isolated EVs. Asthma was induced in 43 male Balb/c mice, divided into four groups: control, asthmatic (AS), asthmatic plus systemic EVs (EV-S), and asthmatic plus intratracheal EVs (EV-IT). Upon completion of asthma induction, animals were treated with EVs either locally (EV-IT) or intravenously (EV-S). Seven days after, we performed bronchoalveolar lavage (BAL) and the total nuclear cells were counted. The animals were euthanized, and the lungs were collected for histopathological analysis of the airways. The EV-S group showed improvement in only the total BAL cell count compared with the AS group, while the EV-IT group showed significant improvement in almost all evaluated criteria.

Original languageEnglish (US)
Article numbere22200620
JournalBrazilian Archives of Biology and Technology
Volume65
DOIs
StatePublished - 2022

Bibliographical note

Funding Information:
Funding: This study was supported by MCTI/CNPq/MS (grant number 404656/2012-9). We thank CAPES (Ministério da Educação) for Felipe Y.I. Fragoso’s fellowship. Acknowledgments: We would like to thank all the staff of the Núcleo de Tecnologia Celular (PUCPR) for cell preparation and animal procedures; the staff of Centro de Modelos Experimentais (PUCPR) for animal care and transport; the staff of the Instituto Carlos Chagas (Fiocruz-PR) for laboratory support; and the staff of the Laboratório de Anatomia Patológica na Pesquisa Clínica e Experimental at PUCPR for support with lungs and stained slides. Conflicts of Interest: The authors declare no conflict of interest.

Funding Information:
This study was supported by MCTI/CNPq/MS (grant number 404656/2012-9). We thank CAPES (Minist?rio da Educa??o) for Felipe Y.I. Fragoso?s fellowship

Publisher Copyright:
© 2022. by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY NC) license (https://creativecommons.org/licenses/by-nc/4.0/)

Keywords

  • Airway remodeling
  • Asthma
  • Balb/c mice
  • Extracellular vesicles
  • Pulmonary inflammation
  • Stromal cells

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