Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases

Abstract

Introduction Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. Areas covered The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. Expert opinion While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification.

Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model

“…A number of studies have demonstrated the beneficial effects of MSC-EVs in vitro and in animal models of lung, kidney, and liver diseases [37,38]. Furthermore, several studies have shown that EVs exert their therapeutic effects by transferring their mRNA to diseased cells [20,29,39,40].…”

<p>Sodium Selenite Improves The Therapeutic Effect Of BMSCs Via Promoting The Proliferation And Differentiation, Thereby Promoting The Hematopoietic Factors</p>

“…According to the International Society for Stem Cell Research (ISSCR), MSCs are usually characterized based on the following three criteria: 1) plastic adhesion ability in standard culture; 2) non-expression or low expression of CD45, CD34, CD14, CD11b, CD79a, CD19, and HLA-DR and high expression of CD105, CD73, and CD90; and 3) ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro. 21 Investigation of the morphology of the isolated cells showed that they displayed homogeneous elongated ( Figure 1A) structures, and the BMSCs expressed CD44, CD73, CD90, and CD105, but not CD45. These results showed that we successfully separated the BMSCs from the mice bone marrow ( Figure 1B).…”

Mesenchymal stem/stromal cells: the therapeutic effects in animal models of acute pulmonary diseases

“…Li et al demonsterated that intravenous use of MSCs in the treatment of acute pulmonary inflammation induced by H9N2 avian influenza in mice caused a significant reduction in plasma and BAL inflammatory factors (IL-1α, IL-6, TNF-α and IFN-γ) and a the corresponding increase in anti-inflammatory cytokine (IL-10), 3 days after cell therapy. The researchers stated that this treatment method reduces the lung permeability and the concentration of the alveolar fluid proteins [52,81].…”