Cardiopulmonary and histological characterization of an acute rat lung injury model demonstrating safety of mesenchymal stromal cell infusion. Cytotherapy 2016 Apr;18(4):536-45
Date
03/15/2016Pubmed ID
26971682Pubmed Central ID
PMC4811186DOI
10.1016/j.jcyt.2016.01.010Scopus ID
2-s2.0-84960103200 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
BACKGROUND AIMS: In the field of cellular therapy, potential cell entrapment in the lungs following intravenous administration in a compromised or injured pulmonary system is an important concern that requires further investigation. We developed a rat model of inflammatory and fibrotic lung disease to mimic the human clinical condition of obliterative bronchiolitis (OB) and evaluate the safety of intravenous infusion of mesenchymal stromal cells (MSCs). This model was used to obtain appropriate safety information and functional characterization to support the translation of an ex vivo-generated cellular product into human clinical trials. To overcome spontaneous recovery and size limitations associated with current animal models, we used a novel multiple dose bleomycin strategy to induce lasting lung injury in rats.
METHODS: Intratracheal instillation of bleomycin was administered to rats on multiple days. MSCs were intravenously infused 7 days apart. Detailed pulmonary function tests including forced expiratory volume, total lung capacity, and invasive hemodynamic measurements were conducted to define the representative disease model and monitor cardiopulmonary hemodynamic consequences of the cell infusion. Post-euthanasia assessments included a thorough evaluation of lung morphology and histopathology.
RESULTS: The double dose bleomycin instillation regimen resulted in severe and irreversible lung injury and fibrosis. Cardiopulmonary physiological monitoring reveled that no adverse events could be attributed to the cell infusion process.
DISCUSSION: Although our study did not show the infusion of MSCs to result in an improvement in lung function or rescue of damaged tissue this study does confirm the safety of MSC infusion into damaged lungs.
Author List
Braun RK, Koch JM, Hacker TA, Pegelow D, Kim J, Raval AN, Schmuck EG, Schwahn DJ, Hei DJ, Centanni JM, Eldridge M, Hematti PAuthor
Peiman Hematti MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Acute Lung InjuryAnimals
Bleomycin
Disease Models, Animal
Heart Rate
Humans
Infusions, Intravenous
Lung
Male
Mesenchymal Stem Cell Transplantation
Myocardium
Rats
Rats, Sprague-Dawley
Respiratory Function Tests
