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Stem Cells Transl Med. 2015 Oct;4(10):1199-213. doi: 10.5966/sctm.2015-0021. Epub 2015 Aug 18.

In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome.

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  • 1Departments of Molecular Medicine and Surgery, Cardiothoracic Surgery and Anesthesia, and Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Internal Medicine, Hematology and Oncology, University of Erlangen-Nuremberg, Erlangen, Germany; Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, Italy; Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, Department of Oncology-Pathology, Department of Medical Biochemistry and Biophysics, and Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden; Center for Diseases of Aging, Vaccine and Gene Therapy Institute Florida, Port St. Lucie, Florida, USA; Exosome Diagnostics Inc., New York, New York, USA; Departments of Cardiothoracic Surgery, Hematology, and Immunology, Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden; Ludwig Institute for Cancer Research, Stockholm, Sweden; Health Sciences Research Facility, Department of Medicine, University of Vermont, Burlington, Vermont, USA.
  • 2Departments of Molecular Medicine and Surgery, Cardiothoracic Surgery and Anesthesia, and Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Internal Medicine, Hematology and Oncology, University of Erlangen-Nuremberg, Erlangen, Germany; Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, Italy; Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, Department of Oncology-Pathology, Department of Medical Biochemistry and Biophysics, and Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden; Center for Diseases of Aging, Vaccine and Gene Therapy Institute Florida, Port St. Lucie, Florida, USA; Exosome Diagnostics Inc., New York, New York, USA; Departments of Cardiothoracic Surgery, Hematology, and Immunology, Genetics and Pathology, Uppsala University Hospital, Uppsala, Sweden; Ludwig Institute for Cancer Research, Stockholm, Sweden; Health Sciences Research Facility, Department of Medicine, University of Vermont, Burlington, Vermont, USA Katarina.Leblanc@ki.se.

Abstract

Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms 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 2×10(6) 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 the MSCs demonstrated a broad anti-inflammatory 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.

SIGNIFICANCE:

This article describes the cases of two patients with severe refractory adult respiratory syndrome (ARDS) who failed to improve after both standard life support measures, including mechanical ventilation, and additional measures, including extracorporeal ventilation (i.e., in a heart-lung machine). Unlike acute forms of ARDS (such in the current NIH-sponsored study of mesenchymal stromal cells in ARDS), recovery does not generally occur in such patients.

©AlphaMed Press.

KEYWORDS:

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

PMID:
26285659
[PubMed - indexed for MEDLINE]
PMCID:
PMC4572899
[Available on 2016-10-01]
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