In vivo effects of mesenchymal stromal cells in two patients with severe acute respiratory distress syndrome

Oscar E. Simonson, Dimitrios Mougiakakos, Nina Heldring, Giulio Bassi, Henrik J. Johansson, Magnus Dalén, Regina Jitschin, Sergey Rodin, Matthias Corbascio, Samir El Andaloussi, Oscar P B Wiklander, Joel Z. Nordin, Johan Skog, Charlotte Romain, Tina Koestler, Laila Hellgren-Johansson, Petter Schiller, Per Olof Joachimsson, Hans Hägglund, Mattias MattiasmattssonJanne Lehtiö, Omid R. Faridani, Rickard Sandberg, Olle Korsgren, Mauro Krampera, Daniel J. Weiss, Karl Henrik Grinnemo, Katarina Le Blanc

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties.However,manybasic questions concerning theirmechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti-inflammatory actions. Both patients received 2×106 cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar-capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of theMSCs demonstrated a broad antiinflammatory capacity, including suppression of T-cell responses and induction of regulatory phenotypes in T cells,monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation.

Original languageEnglish (US)
Pages (from-to)1199-1213
Number of pages15
JournalStem Cells Translational Medicine
Volume4
Issue number10
DOIs
StatePublished - Oct 1 2015

Bibliographical note

Publisher Copyright:
© AlphaMed Press.

Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.

Keywords

  • Acute respiratory distress syndrome
  • Bone marrow stromal cells
  • Cell transplantation
  • Cellular therapy
  • Clinical translation
  • Pulmonary diseases
  • Respiratory tract
  • Stem cells

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