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Cell therapy for ARDS: efficacy of endobronchial versus intravenous administration and biodistribution of MAPCs in a large animal model
  1. Nayra Cardenes1,2,
  2. Paola Aranda-Valderrama1,2,
  3. Jonathan P Carney3,
  4. Jacobo Sellares Torres1,2,4,
  5. Diana Alvarez1,2,
  6. Ergin Kocydirim5,6,
  7. Julie A Wolfram Smith7,
  8. Antony E Ting7,
  9. Luigi Lagazzi5,
  10. Zheming Yu3,
  11. Scott Mason3,
  12. Ernesto Santos3,
  13. Brian J Lopresti3 and
  14. Mauricio Rojas1,2,6
  1. 1 The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases, Pittsburgh, Pennsylvania, USA
  2. 2 Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
  3. 3 Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
  4. 4 Interstitial Lung Disease Program, Servei de Pneumología, Institut clinic respiratori, Hospital Clínic, Barcelona, Spain
  5. 5 Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
  6. 6 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  7. 7 Cardiopulmonary Program at Athersys, Inc, Cleveland, Ohio, USA
  1. Correspondence to Dr Mauricio Rojas; rojasm{at}upmc.edu

Abstract

Introduction Bone marrow-derived multipotent adult progenitor cells (MAPCs) are adult allogeneic adherent stem cells currently investigated clinically for use in acute respiratory distress syndrome (ARDS). To date, there is no agreement on which is the best method for stem cells delivery in ARDS. Here, we compared the efficacy of two different methods of administration and biodistribution of MAPC for the treatment of ARDS in a sheep model.

Methods MAPC were labelled with [18F] fluoro-29-deoxy-D-glucose and delivered by endobronchial (EB) or intravenous route 1 hour after lipopolysaccharide infusion in sheep mechanically ventilated. PET/CT images were acquired to determine the biodistribution and retention of the cells at 1 and 5 hours of administration.

Results The distribution and retention of the MAPC was dependent on the method of cell administration. By EB route, PET images showed that MAPC remained at the site of administration and no changes were observed after 5 hours, whereas with intravenous route, the cells had broad biodistribution to different organs, being the lung the main organ of retention at 1 and 5 hours. MAPC demonstrated an equal effect on arterial oxygenation recovery by either route of administration.

Conclusion The EB or intravenous routes of administration of MAPC are both effective for the treatment of ARDS in an acute sheep model, and the effect of MAPC therapy is not dependent of parenchymal integration or systemic biodistribution.

  • Multipotent Adult Progenitor Cells (MAPC)
  • Mesenchymal stem cell (MSC)
  • lung injury
  • Acute Respiratory Distress Syndrome (ARDS)

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0

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Footnotes

  • NC and PA-V contributed equally.

  • Contributors NC designed and analysed, coordinated the experiments and wrote the manuscript; PAV and JS analysed data and wrote the manuscript; JPC, DA, ZY, ES and BJL analysed data; EK, LL and SM conducted experiments; JAWS and AET provided reagents; MR conceived and designed this study, analysed data and wrote the manuscript.

  • Funding This work was supported by National Institute of Health grant RO1 BMJ Open Respiratory Research HL123766-01A1.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The Institutional Animal Care and Use Committee (IACUC) for Animal Research of the University of Pittsburgh approved all experimental procedures in advance. Bone marrow aspirates were acquired with consent and in accordance with 21 CFR Part 1271 Human Cells, Tissues, and Cellular and Tissue Based Products and approved by the Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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