Prospects and progress in cell therapy for acute respiratory distress syndrome

ABSTRACT

Introduction: Despite progress in understanding the pathophysiology of the acute respiratory distress syndrome (ARDS), it remains a devastating clinical disorder associated with high mortality rates, and those who survive can experience significant long-term morbidity. Recent advances in the management of ARDS have mostly been achieved in supportive care, including the use of protective mechanical ventilation, neuromuscular blocking agents, prone positioning, and conservative fluid strategies. However, to date, no pharmacologic therapy has been able to act effectively on disease-specific pathways or to reduce mortality. In this context, current advances in understanding the potential roles of alternative approaches, such as cell therapy, offer new hope for ARDS.

Areas covered: This review discusses the use of mesenchymal stromal (stem) cells (MSCs) in pre-clinical experimental models of ARDS and in ongoing clinical trials.

Expert opinion: Through the secretion of soluble mediators and extracellular vesicles, MSCs have been shown to modulate inflammation, enhance bacterial clearance, and reduce organ injury and death, making them a potential novel treatment for ARDS. Initial clinical trials have demonstrated the safety of MSC administration in patients with ARDS but further investigations are required to further characterize the efficacy profile of these therapies.

KEYWORDS:

• Mesenchymal stromal cells
• extracellular vesicles
• conditioned media
• acute respiratory distress syndrome
• experimental study
• clinical trials
• acute lung injury
• immunomodulation
• potentialization

Article highlights

• Acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and no current treatment is effective.

• Mesenchymal stromal cell (MSC) therapy has been successfully tested in experimental ARDS.

• MSCs modulate inflammation, enhance bacterial clearance, and reduce organ injury and death.

• MSCs act through secretion of soluble factors and extracellular vesicles, as well as through intercellular connections.

• Clinical trials have shown that MSC therapy is safe.

This box summarizes key points contained in the article.

Declaration of interest

DJ Weiss has received research funding from Athersys Inc. and from United Therapeutics Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

The authors research is funded by the Centers of Excellence Program (PRONEX-FAPERJ), the Brazilian Council for Scientific and Technological Development (CNPq), the Carlos Chagas Filho Rio de Janeiro State Research Foundation (FAPERJ), the Department of Science and Technology (DECIT)/ Brazilian Ministry of Health, and the Coordination for the Improvement of Higher Level Personnel (CAPES).