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Current understanding of the therapeutic benefits of mesenchymal stem cells in acute respiratory distress syndrome

  • Miquéias Lopes-Pacheco
  • Chiara Robba
  • Patricia Rieken Macêdo RoccoEmail author
  • Paolo PelosiEmail author
Original Article

Abstract

The acute respiratory distress syndrome (ARDS) is a multifaceted lung disorder in which no specific therapeutic intervention is able to effectively improve clinical outcomes. Despite an improved understanding of molecular mechanisms and advances in supportive care strategies, ARDS remains associated with high mortality, and survivors usually face long-term morbidity. In recent years, preclinical studies have provided mounting evidence of the potential of mesenchymal stem cell (MSC)-based therapies in lung diseases and critical illnesses. In several models of ARDS, MSCs have been demonstrated to induce anti-inflammatory and anti-apoptotic effects, improve epithelial and endothelial cell recovery, and enhance microbial and alveolar fluid clearance, thus resulting in improved lung and distal organ function and survival. Early-stage clinical trials have also demonstrated the safety of MSC administration in patients with ARDS, but further, large-scale investigations are required to assess the safety and efficacy profile of these therapies. In this review, we summarize the main mechanisms whereby MSCs have been shown to exert therapeutic effects in experimental ARDS. We also highlight questions that need to be further elucidated and barriers that must be overcome in order to efficiently translate MSC research into clinical practice.

Keywords

Acute respiratory distress syndrome Biomarkers Cell therapy Clinical trials Mesenchymal stem cells Lung Paracrine effects 

Abbreviations

Ang-1

Angiopoietin-1

ARDS

Acute respiratory distress syndrome

ATP

Adenosine triphosphate

ECMO

Extracorporeal membrane oxygenation

ENaC

Epithelial sodium channel

EV

Extracellular vesicle

FGF

Fibroblast growth factor

HGF

Hepatocyte growth factor

HLA

Human leukocyte antigen

IFN

Interferon

IL

Interleukin

IL-1RN

IL-1 receptor antagonist

KGF

Keratinocyte growth factor

LXA4

Lipoxin A4

MIP

Macrophage inflammatory protein

MMP

Metalloproteinase

MSCs

Mesenchymal stem cells

PGE2

Prostaglandin E2

TGF-β

Transforming growth factor-β

TIMP

Tissue inhibitor of metalloproteinase

TNF

Tumor necrosis factor

TSG-6

TNF-inducible gene-6

TLR

Toll-like receptor

VEGF

Vascular endothelial growth factor

Notes

Funding information

This study was supported by the Brazilian Council for Scientific and Technological Development (CNPq), the Rio de Janeiro State Research Foundation (FAPERJ), the Department of Science and Technology (DECIT)/Brazilian Ministry of Health, and the National Institute of Science and Technology for Regenerative Medicine (INCT-Regenera).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of BiophysicsFederal University of Rio de JaneiroRio de JaneiroBrazil
  2. 2.National Institute of Science and Technology for Regenerative MedicineRio de JaneiroBrazil
  3. 3.Anesthesia and Intensive CareSan Martino Policlinico Hospital, IRCCS for Oncology and NeurosciencesGenoaItaly
  4. 4.Department of Surgical Sciences and Integrated DiagnosticsUniversity of GenoaGenoaItaly

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