Cardiopulmonary and histological characterization of an acute rat lung injury model demonstrating safety of mesenchymal stromal cell infusion

Rudolf K. Braun, Jill M. Koch, Timothy A. Hacker, David Pegelow, Jaehyup Kim, Amish N. Raval, Eric G. Schmuck, Denise J. Schwahn, Derek J. Hei, John M. Centanni, Marlowe Eldridge, Peiman Hematti

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

ackground 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.

Original languageEnglish (US)
Pages (from-to)536-545
Number of pages10
JournalCytotherapy
Volume18
Issue number4
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

Keywords

  • Cardiac function
  • Cardiopulmonary characterization
  • Cellular therapy
  • Lung injury
  • MSC
  • Mesenchymal stromal cells
  • Pulmonary function
  • Safety
  • Stem cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation

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