Mesenchymal stromal cell infusion rapidly attenuates systemic inflammation in patients with chronic obstructive pulmonary disease   — ASN Events
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  3. Mesenchymal stromal cell infusion rapidly attenuates systemic inflammation in patients with chronic obstructive pulmonary disease  

Mesenchymal stromal cell infusion rapidly attenuates systemic inflammation in patients with chronic obstructive pulmonary disease   (#151)

Jesse D Armitage 1 2 , Dino BA Tan 1 2 , Yuben P Moodley 1 2 3
  1. Stem cell unit, Institute of Respiratory Health, Perth, Western Australia, Australia
  2. University of Western Australia, Perth, WA, Australia
  3. Department of Respiratory Medicine, Fiona Stanley Hospital, Perth, Western Australia, Australia

Introduction: Chronic obstructive pulmonary disease (COPD) is the most common respiratory disease in the world and is driven by chronic systemic inflammation. Mesenchymal stromal cells (MSCs) are immunomodulating cells, and stimulate a broad range of anti-inflammatory responses, particularly from T regulatory cells (Treg) and regulatory monocytes in circulation. MSC infusions have shown success in numerous clinical trials for improving patient outcomes in inflammatory-driven diseases as a novel immune-based therapy. Therefore, we hypothesise that MSC infusion will alleviate chronic inflammation in patients with COPD. 

Methods: Radiolabelled MSC were infused intravenously into patients with stable COPD (n=9) and tracked by CT scan across the first week post-fusion. Additionally, peripheral blood was collected across the first week. Systemic inflammatory (sTNFR1, sCD163, IL-6, IP-10) and oxidative stress (F2-Isoprostane) biomarkers were measured in plasma across 7 days post-infusion by enzyme-linked immunosorbent assay and gas chromatography-mass spectrometry respectively. Proportions of FoxP3+CD25+ Treg, CD123+ plasmacytoid dendritic cells (pDC), CD11c+ myeloid DCs (mDC) and monocyte subsets were measured by flow cytometry.

Results: MSCs first localised in the lungs from 0-24 hours post-infusion and then trafficked to the liver, spleen and bone marrow from day 1-7. Markers of inflammation and pro-inflammatory mDC were significantly reduced after MSC infusion. Treg and immune regulatory pDC proportions were increased. Monocyte subsets demonstrated a shift to a more anti-inflammatory phenotype. 

Conclusion: We provide novel data showing that infused MSC migrate quickly to the inflamed lung followed by migration to other sites of immune regulation. MSC infusion also elicited a range of systemic anti-inflammatory responses. Further characterisation of these systemic immunological changes will provide a deeper understanding of these mechanisms, however our results show promising potential for using MSC infusions as a novel immune-based therapy for COPD patients.

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