The potential of mesenchymal stem cell therapy for chronic lung disease

ABSTRACT

Introduction: Mesenchymal stem/stromal cells (MSCs) have been shown to improve lung function and survival in chronic inflammatory lung diseases, including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), and silicosis.

Areas covered: This review covers rationale for the use of MSC therapy, along with preclinical studies and clinical trials with MSC therapy in chronic lung diseases.

Expert opinion: MSC therapy holds promise for the treatment of chronic lung diseases, mainly when administered at early stages. In clinical trials, MSC administration was safe, but associated with limited effects on clinical outcomes. Further studies are required to elucidate unresolved issues, including optimal MSC source and dose, route of administration, and frequency (single vs. multiple-dose regimens). A better understanding of the mechanisms of MSC action, local microenvironment of each disease, and development of strategies to potentiate the beneficial effects of MSCs may improve outcomes.

KEYWORDS:

• Mesenchymal stromal cells
• extracellular vesicles
• conditioned media
• COPD
• clinical trials

Article highlights

• Chronic lung diseases carry high morbidity and mortality rates, and o current treatment is able to reverse pathological changes or halt disease progression. Mesenchymal stromal cells (MSCs) have been used in potentially curative approaches.

• MSCs have anti-inflammatory, microbicidal, angiogenic, and antifibrotic effects in preclinical studies.

• MSCs improve lung function and reduce mortality in models of chronic lung diseases.

• Despite the plastic effects of MSCs, they are known to act trough secretion of soluble factors, extracellular vesicles, and mitochondria transfer.

• Clinical trials showed MSCs are safe in chronic lung diseases, but clinical effects are modest compared to the experimental setting.

• Several strategies have been used to potentiate MSC effects for lung diseases.

Acknowledgments

The authors would like to express their gratitude to Mrs. Moira Elizabeth Schottler (Rio de Janeiro) and Mr. Filippe Vasconcellos (São Paulo), Brazil, for their assistance in editing the manuscript

Authors’ contributions

FFC and PRMR contributed to the literature review and the drafting of the manuscript. Both authors read and approved the final manuscript.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded 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, the Coordination for the Improvement of Higher Education Personnel (CAPES), and the National Institute of Science and Technology for Regenerative Medicine.