Abstract
The number of publications studying the therapeutic use of stem cells has steadily increased since 2000. Compared to other applications, there has been little interest in the evaluation of mesenchymal stem cells (MSCs) and MSC-derived products (mostly extracellular vesicles) for the treatment of respiratory diseases. Due to the lack of efficient treatments for acute respiratory distress syndrome caused by infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the action of MSCs has also been studied. This review describes mode of action and use of MSCs and MSC-derived products in the treatment of lung diseases including the respective advantages and limitations of the products. Further, issues related to standardized production are addressed. Administration by inhalation of MSCs, compared to intravenous injection, could decrease cell damage by shear stress, eliminate the barrier to reach target cells in the alveoli, prevent thrombus formation in the pulmonary vasculature and retention in filter for extracorporeal membrane oxygenation. There is more feasible to deliver extracellular vesicles than MSCs with inhalers, offering the advantage of non-invasive and repeated administration by the patient. Major obstacles for comparison of results are heterogeneity of the products, differences in the treatment protocols and small study cohorts.
Highlights
Due to the lack of efficient treatments for acute respiratory distress syndrome caused by infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the action of mesenchymal stem cells (MSCs) has been studied
This review describes mode of action and use of MSCs and MSC-derived products in the treatment of lung diseases including the respective advantages and limitations of the products
Much fewer clinical trials than with MSCs have been started assessing the effects of conditioned media for the treatment of lung diseases but effects of conditioned media obtained from MSCs have been evaluated in preclinical models
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Compared to the few diseases, in which stem cell products are used, the panel of diseases that could be treated with adult stem cells is broad and includes cancer, autoimmune diseases, cardiovascular diseases, ocular diseases, immunodeficiencies, neurodegenerative diseases, anemias, wound healing, metabolic diseases and liver diseases [3]. Pharmaceutics 2021, 13, 232 evaluation in ~1000 clinical trials with main indication for neurological, joint and cardiovascular diseases [6]. They find application in tissue reconstruction [7]. Conditioned media obtained from MSCs, which contains secretome, microvesicles or exosomes, is predominantly used for regenerative purposes, for example, stroke, brain/spinal cord injury, bone/cartilage defect, skin/hair regeneration, wounds, myocardial infarction, neurodegenerative diseases and liver failure [8]. Potential differences in the biological effects of these products upon intravenous and inhaled administration will be discussed
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