Lucero Alvarado
Abstract
This work is partly presented at 11th World Congress and Expo on Cell & Stem Cell Research on March 25-26, 2019 held at Orlando, USA Vol.4 No.3 Extended Abstract Journal of Cell and Developmental Biology 2020 Stem Cell Conference 2019_ Evaluating the therapeutic potential of mesenchymal stem cells in an in vitro model of alveolar barrier_ Lucero Alvarado_ United States Army Institute of Surgical Research (USAISR)_ USA Lucero Alvarado United States Army Institute of Surgical Research (USAISR), USA Acute Respiratory Distress Syndrome (ARDS) is a form of acute lung injury that causes morbidity and mortality in ill patients. Current therapies for ARDS include lung protective ventilation and fluid clearance, but do not treat the underlying cause. Mesenchymal stem cells (MSCs) have been proposed as a promising form of therapy to treat ARDS. Currently, it is unknown which MSC type is best-suited to treat ARDS. The goals of these studies 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 the ARDS-like injury. To accomplish this, we utilized injurious signals typically manifested in ARDS, such as low oxygen concentration (i.e., hypoxia) and lipopolysaccharide (LPS). LPS is a bacterial endotoxin that induces ARDS in vivo and mimics infection in vitro. We then subjected a co-culture system of lung epithelial and endothelial cells to these signals to induce the injury. Finally, we added MSCs to this sustem to evaluate their ability to mitigate the injury. After subjecting the co-culture system to hypoxia and LPS, we observed an increase in apoptosis as evidenced by increase in mitochondrial membrane potential and Annexin V analysis. In comparing MSC types, both BM-MSCs and AD-MSCs suppressed T-cell proliferation in a mixed lymphocyte reaction assay; however, AD-MSCs were more potent following a LPS challenge. Additionally, both cell types diminished the secretion of the pro-inflammatory cytokines IFN-γ, IL-13, IL-1α, and IL-1β; yet, unlike BM-MSCs, AD-MSCs showed a significant increase in the anti-inflammatory IL-1RA after LPS exposure. Following the addition of AD-MSCS, there was a significant decrease in protein permeability in the coculture system. Taken together, in the co-culture system, we successfully established an injurios environment rmimicking an ARDS-like condition. Compared to BM-MSCs, AD-MSCs appear to be a more suitable candidate for ARDS due to their superior anti-inflammatory function. Therefore, Addition of AD-MSCs to an in vitro co-culture system of ARDS mitigated the injury as evidenced by reduction in membrane permeability. Mesenchymal stem cells (MSCs) are an example of tissue or 'adult' stem cells. They are ‘multipotent’, meaning they can produce more than one type of specialized cell of the body, but not all types. MSCs make the various specialized cells found within the skeletal tissues. For example, they will differentiate − or specialize − into cartilage cells (chondrocytes), bone cells (osteoblasts) and fat cells (adipocytes). These specialized cells each have their own characteristic shapes, structures and functions, and every belongs during a particular tissue. Some MSC research is additionally exploring therapies for other diseases.