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Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia
  1. Sven Asmussen1,
  2. Hiroshi Ito1,
  3. Daniel L Traber1,
  4. Jae W Lee2,
  5. Robert A Cox1,
  6. Hal K Hawkins1,
  7. Daniel F McAuley2,3,
  8. David H McKenna4,
  9. Lillian D Traber1,
  10. Hanjing Zhuo2,
  11. Jennifer Wilson2,
  12. David N Herndon5,
  13. Donald S Prough1,
  14. Kathleen D Liu2,
  15. Michael A Matthay2,
  16. Perenlei Enkhbaatar1
  1. 1Department of Anesthesiology, The University of Texas Medical Branch, Galveston, Texas, USA
  2. 2Departments of Medicine & Anesthesiology, Cardiovascular Research Institute, The University of California San Francisco, San Francisco, California, USA
  3. 3Centre for Infection and Immunity, The Queen's University of Belfast, Belfast, Northern Ireland, UK
  4. 4Production Assistance in Cellular Therapy, University of Minnesota, Saint Paul, Minnesota, USA
  5. 5Shriners Hospital for Children, Galveston, Texas, USA
  1. Correspondence to Dr Perenlei Enkhbaatar, Department of Anesthesiology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555—1102, USA; peenkhba{at}


Background Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS.

Methods Adult sheep (30–40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×1011 CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×106 hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×106 hMSCs/kg, n=4.

Results By 24 h, the PaO2/FiO2 ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO2/FiO2 of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9–5.8] vs control: 6.7 g wet/g dry [IQR 6.4–7.5] (p=0.01)). The hMSCs had no adverse effects.

Conclusions Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS.

Trail registration number: NCT01775774 for Phase 1. NCT02097641 for Phase 2.

  • ARDS

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