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

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.

Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models

“…C57BL/6 (B6) mice were purchased from CLEA Japan Inc. (Tokyo, Japan) and maintained under conventional conditions at the Nagasaki University Animal Center. Induction of emphysema was performed according to a previous protocol established as previously reported ( 19 , 20 ). Briefly, the animals were treated with 3% isoflurane under oxygen anesthesia and challenged with intranasal instillation of 30 μg porcine pancreatic elastase (catalog number 058-05361; FUJIFILM Wako Pure Chemical Corporation, Osaka, Japan) in 50 µl of 0.9% saline solution.…”