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Administration of mesenchymal stem cells during ECMO results in a rapid decline in oxygenator performance
  1. Jonathan Edward Millar1,
  2. Viktor von Bahr1,2,
  3. Maximillian V Malfertheiner1,3,
  4. Katrina K Ki1,
  5. Meredith A Redd4,
  6. Nicole Bartnikowski1,
  7. Jacky Y Suen1,
  8. Danny Francis McAuley5,
  9. John F Fraser1
  1. 1Critical Care Research Group, University of Queensland, Brisbane, Queensland, Australia
  2. 2Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care Medicine, Karolinska Institutet, Stockholm, Sweden
  3. 3Department of Internal Medicine II, Cardiology and Pneumology, University Medical Center Regensburg, Regensburg, Germany
  4. 4Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
  5. 5Queen’s University Belfast, Wellcome-Wolfson Centre for Experimental Medicine, Belfast, UK
  1. Correspondence to Dr Jonathan Edward Millar, Critical Care Research Group, University of Queensland, The Prince Charles hospital, Brisbane QLD 4032, Australia; j.millar{at}doctors.org.uk

Abstract

Mesenchymal stem cells (MSCs) have attracted attention as a potential therapy for Acute Respiratory Distress Syndrome (ARDS). At the same time, the use of extracorporeal membrane oxygenation (ECMO) has increased among patients with severe ARDS. To date, early clinical trials of MSCs in ARDS have excluded patients supported by ECMO. Here we provide evidence from an ex-vivo model of ECMO to suggest that the intravascular administration of MSCs during ECMO may adversely impact the function of a membrane oxygenator. The addition of clinical grade MSCs resulted in a reduction of flow through the circuit in comparison to controls (0.6 ±0.35 L min-1vs 4.12 ± 0.03 L min-1, at 240 minutes) and an increase in the transoygenator pressure gradient (101±9 mmHg vs 21±4 mmHg, at 240 minutes). Subsequent immunohistochemistry analysis demonstrated quantities of MSCs highly adherent to membrane oxygenator fibres. This study highlights the potential harm associated with MSC therapy during ECMO and suggests further areas of research required to advance the translation of cell therapy in this population.

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Footnotes

  • Contributors JEM, DFM and JFF conceived and designed the study. VvB and MVM designed and modified the ex-vivo ECMO model. JEM, VvB and MVM conducted the ex-vivo experiments. KKK, MAR, NB and JYS analysed the generated samples. All authors have participated in the drafting and critical revision of the manuscript.

  • Funding This study was supported by the Intensive Care Society (UK) New Investigator Award and by the National Health and Medical Research Council (NHMRC), Australia (APP1079421). VvB is funded by Gålöstiftelsen Foundation, Olle Enqvist Byggmästare Foundation, Karolinska Institutet Fernström Foundation, and the Royal Swedish Academy of Sciences, Claes Adelsköld Foundation.

  • Competing interests Cynata Therapeutics provided mesenchymal stem cells in kind to this study. The company was not involved in the commission, design or analysis of the study.

  • Ethics approval The study was approved by the Metro North Ethics Committee (HREC/16/QPCH/221).

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

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