Journal Article

Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model

De Palma, Raffaele, Esposito, Grazia, Urbanek, Konrad, Matteis, Maria, Russo, Rosa, Tartaglione, Gioia, D’Agostino, Bruno, De Angelis, Antonella, Rossi, Francesco, Spaziano, Giuseppe, Piegari, Elena, Cappetta, Donato

2016

Overview

The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs) can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce. To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model. GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro. Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties. Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue remodeling.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Airway management / Airway obstruction / Alveoli / Animal models / Animals / Anti-inflammatory agents / Asthma / Biology and Life Sciences / Bone marrow / Bronchoalveolar Lavage Fluid - chemistry / Bronchoalveolar Lavage Fluid - immunology / Bronchus / Care and treatment / Cytokines / Diagnosis / Epithelium / Gene Expression / Genes, Reporter / Green Fluorescent Proteins - genetics / Green Fluorescent Proteins - metabolism / Homeostasis / Immunomodulation / In vivo methods and tests / Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics / Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology / Inflammation / Interleukin 10 / Interleukin 13 / Interleukin 4 / Interleukin 5 / Interleukin-10 - genetics / Interleukin-10 - immunology / Interleukin-13 - genetics / Interleukin-13 - immunology / Interleukin-4 - genetics / Interleukin-4 - immunology / Interleukin-5 - genetics / Interleukin-5 - immunology / Intubation, Intratracheal / Lung - immunology / Lung - pathology / Lung diseases / Medicine / Medicine and Health Sciences / Mesenchymal Stem Cell Transplantation / Mesenchymal stem cells / Mesenchymal Stromal Cells - cytology / Mesenchymal Stromal Cells - immunology / Mesenchyme / Metaplasia / Mice / Mice, Inbred BALB C / Mucus / Muscles / Neurokinin / Neuropeptides / Ovalbumin / Pharmacology / Physiological aspects / Properties / Receptors / Receptors, Neurokinin-1 - genetics / Receptors, Neurokinin-1 - immunology / Receptors, Neurokinin-2 - genetics / Receptors, Neurokinin-2 - immunology / Research and Analysis Methods / Respiratory Hypersensitivity - chemically induced / Respiratory Hypersensitivity - immunology / Respiratory Hypersensitivity - pathology / Respiratory Hypersensitivity - therapy / Respiratory tract / Restoration / Smooth muscle / Stem cells / Studies / Tachykinins / Transplants & implants / Tryptophan 2,3-dioxygenase