Mesenchymal Stem Cells from COPD Patients Are Capable of Restoring Elastase-Induced Emphysema in a Murine Experimental Model

Author:

Río Carlos1ORCID,Jahn Andreas K.1,Martin-Medina Aina1,Calvo Bota Alba Marina1,De Francisco Casado Mª Teresa2,Pont Antona Pere Joan2,Gigirey Castro Orlando3,Carvajal Ángel Francisco3,Villena Portella Cristina14,Gómez Bellvert Cristina5,Iglesias Amanda16ORCID,Calvo Benito Javier78,Gayà Puig Antoni78ORCID,Ortiz Luis A.9,Sala-Llinàs Ernest1610

Affiliation:

1. Inflammation, Repair and Cancer of Respiratory Diseases (i-Respire), Fundació Institut d’ Investigació Sanitària Illes Balears (IdISBa), 07120 Palma, Spain

2. Estabulary, Scientific-Technical Services, Universitat de les Illes Balears (UIB), 07122 Palma, Spain

3. Department of Thoracic Surgery, Hospital Universitari Son Espases, 07120 Palma, Spain

4. CIBERES Pulmonary Biobank Consortium, Hospital Universitari Son Espases, 07120 Palma, Spain

5. Department of pathology, Hospital Universitari Son Espases, 07120 Palma, Spain

6. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain

7. Banc de Teixits, Blood and Tissue Bank of the Balearic Islands (FBSTIB), 07120 Palma, Spain

8. Cell Therapy and Tissue Engineering Group (TERCIT), Institut d’ Investigació Sanitària Illes Balears (IdISBa), 07004 Palma, Spain

9. Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA

10. Department of Pulmonary Medicine, Hospital Universitari Son Espases, 07120 Palma, Spain

Abstract

COPD is a chronic lung disease that affects millions of people, declining their lung function and impairing their life quality. Despite years of research and drug approvals, we are still not capable of halting progression or restoring normal lung function. Mesenchymal stem cells (MSC) are cells with extraordinary repair capacity, and MSC-based therapy brings future hope for COPD treatment, although the best source and route of administration are unclear. MSC from adipose tissue (AD-MSC) represents an option for autologous treatment; however, they could be less effective than donor MSC. We compared in vitro behavior of AD-MSC from COPD and non-COPD individuals by migration/proliferation assay, and tested their therapeutic potential in an elastase mouse model. In addition, we tested intravenous versus intratracheal routes, inoculating umbilical cord (UC) MSC and analyzed molecular changes by protein array. Although COPD AD-MSC have impaired migratory response to VEGF and cigarette smoke, they were as efficient as non-COPD in reducing elastase-induced lung emphysema. UC-MSC reduced lung emphysema regardless of the administration route and modified the inflammatory profile in elastase-treated mice. Our data demonstrate equal therapeutic potential of AD-MSC from COPD and non-COPD subjects in the pre-clinical model, thus supporting their autologous use in disease.

Funder

Instituto de Carlos III

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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