Evaluating the Therapeutic Effects of Mesenchymal Stem Cells in an in Vitro Co-Culture System of a Damaged Alveolar Barrier




Alvarado, Lucero

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Acute Respiratory Distress Syndrome (ARDS) is a form of acute lung injury that causes morbidity and mortality in ill patients. Mesenchymal stem cells (MSCs) have been proposed as a promising form of therapy to treat ARDS. The goals of this study were therefore three-fold: 1. Create a model of ARDS in vitro; 2. Identify which MSC source, bone marrow (BM) or adipose (AD)-MSC, is more suitable to treat ARDS; and 3. Evaluate the ability of MSCs to mitigate ARDS-like injury in vitro. To accomplish this, we subjected a co-culture system of human lung epithelial and endothelial cells to injurious signals typically manifested in ARDS, such as hypoxia and lipopolysaccharide (LPS). After subjecting the co-culture system to hypoxia and LPS, we observed an increase in apoptosis; upregulation in gene expression of the adhesion molecules, ICAM and VCAM; and an increased secretion of pro-inflammatory mediators. In comparing MSC types, both BM-MSCs and AD-MSCs exhibited a similar therapeutic response; however, AD-MSCs were more potent in arresting T-cell proliferation and in modulating the inflammatory milieu. For these reasons, AD-MSCs were identified as the most appropriate therapeutic source. Following addition of AD-MSCs to the co-culture system resulted in significant decrease in protein permeability and down-regulation of apoptotic genes, BCL-2 and BAX; adhesion molecule, ICAM; and the tissue injury genes TLR-2 and HMGB1. Furthermore, after adding AD-MSCs, secretion of TNF-α, GM-CSF, and IL-6 was significantly inhibited, while the anti-inflammatory IL-1RA was significantly increased. Taken together, AD-MSCs are potent therapeutic tools to mitigate ARDS-like injury in vitro.





Integrative Biology