Mesenchymal stromal cell therapy for chronic lung diseases: experimental and clinical evidence

ABSTRACT

Introduction

Cell therapy has emerged as an alternative option for chronic lung diseases with the highest rates of morbidity and mortality rates worldwide.

Areas covered

This review addresses the definition of mesenchymal stromal cells (MSCs), their properties, mechanisms of action, as well as preclinical and clinical studies that have used cell therapy in chronic lung diseases such as asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, pulmonary arterial hypertension, and silicosis. Ongoing clinical trials are also presented.

Expert opinion

Experimental evidence has shown that MSCs have immunomodulatory and regenerative properties that could rescue impaired lung function and histoarchitecture. Their beneficial effects have been mainly associated with their ability to communicate with target cells through the secretion of soluble mediators and extracellular vesicles or even through transfer of organelles (e.g. mitochondria). MSC-derived conditioned medium, extracellular vesicles and mitochondria induce beneficial effects in selected scenarios. The initial results in clinical trials were modest compared with the experimental results, therefore researchers were encouraged to move from bedside back to bench to develop new strategies able to potentiate the effects of MSCs.

KEYWORDS:

• Clinical trials
• experimental studies
• exosomes
• extracellular vesicles
• mesenchymal stromal cells
• mitochondria transfer
• potentializing

Article highlights

• Mesenchymal stromal cells (MSCs) have been shown to have immunomodulatory, microbicide, antifibrotic and regenerative properties.

• Due to the plasticity of MSCs, regenerative properties were believed to be the main mechanism of action; however, benefits are now attributed to their paracrine and endocrine effects. The interaction of MSCs with target cells (cell-to-cell contact) and secretion of soluble mediators and extracellular vesicles as well as mitochondrial transfer have gained the spotlight in the last decade.

• Preclinical evidence shows that MSC therapy reduces inflammation and fibrosis and improves lung function in models of asthma emphysema, pulmonary arterial hypertension, and silicosis. Several studies have been performed to potentiate MSCs in models of chronic lung diseases.

• In experimental chronic obstructive pulmonary disease, MSCs were able to reduce inflammation and mean alveolar diameter and improve pulmonary-associated cardiovascular dysfunction and lung function in different models (cigarette smoke, elastase, papain).

• MSCs were able to reduce inflammation-associated collagen deposition and to improve lung function in models of lung fibrosis (bleomycin, radiation).

• MSCs reduced right ventricular pressure overload, right ventricle dysfunction, and lung pathology in experimental models of pulmonary arterial hypertension (monocrotaline, hypoxia-induced models).

• Cell therapy reduced inflammation, fibrosis and granuloma number and extension, improving lung function in silicosis.

• The initial results in clinical trials were modest compared with experimental results, therefore researchers were encouraged to move from bedside back to bench to develop new strategies able to potentiate the effects of MSCs.

• Therapy with conditioned medium or extracellular vesicles has been shown to induce similar effects as cell therapy in chronic lung diseases, with some particularities in each case.

• Therapy with MSCs or their subproducts has been listed as ongoing in clinical trials: 10 in chronic lung diseases; 3 in asthma; 4 in chronic obstructive pulmonary disease, 2 in idiopathic pulmonary fibrosis and 1 in pulmonary arterial hypertension.

Acknowledgments

The authors would like to express their gratitude to Moira Elizabeth Shottler and Lorna O’Brien (authorserv.com) for editing assistance.

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.

Author contributions

All authors contributed to the literature review, drafting the manuscript, read and approved the final manuscript.

Additional information

Funding

This paper was funded by 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 National Institute of Science and Technology for Regenerative Medicine.