Potential application of mesenchymal stem cells in acute lung injury. Expert Opin Biol Ther 9:1259-1270

University of California, Anesthesiology, 505 Parnassus Avenue, Box 0648, San Francisco, CA 94143-0648, USA.
Expert opinion on biological therapy (Impact Factor: 3.74). 09/2009; 9(10):1259-70. DOI: 10.1517/14712590903213651
Source: PubMed


Despite extensive research into the pathogenesis of acute lung injury and the acute respiratory distress syndrome (ALI/ARDS), mortality remains high at approximately 40%. Current treatment is primarily supportive, with lung-protective ventilation and a fluid conservative strategy. Pharmacologic therapies that reduce the severity of lung injury in experimental studies have not yet been translated into effective clinical treatment options. Therefore, innovative therapies are needed. Recent studies have suggested that bone-marrow-derived multipotent mesenchymal stem cells (MSC) may have therapeutic applications in multiple clinical disorders including myocardial infarction, diabetes, sepsis, hepatic and acute renal failure. Recently, MSC have been studied in several in vivo models of lung disease. This review focuses on first describing the existing experimental literature that has tested the use of MSC in models of ALI/ARDS, and then the potential mechanisms underlying their therapeutic use with an emphasis on secreted paracrine soluble factors. The review concludes with a discussion of future research directions required for potential clinical trials.

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Available from: Naveen Gupta, Jan 29, 2014
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    • "Several studies have reported that MSCs can upregulate the expression of MHC II when exposed to low levels of inflammation and that MSCs function as antigen-presenting cells to stimulate the adaptive immune system [20] [21]. In addition, evidence suggests that MSCs can secrete IL-6 and induce the production of IgG by B lymphocytes in an in vitro setting [18]. In addition, Sun and colleagues [22] reported that the transplantation of MSCs ameliorated ALI in mice by enhancing diminished levels of alveolar CD4+ CD25+ Foxp3+ Treg and by balancing anti-and proinflammatory factors. "
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    ABSTRACT: Microvesicles (MVs) are membrane vesicles that are released by many types of cells and have recently been considered important mediators of cell-to-cell communication. MVs serve as a vehicle to transfer proteins and messenger RNA and microRNA (miRNA) to distant cells, which alters the gene expression, proliferation, and differentiation of the recipient cells. Several studies have demonstrated that mesenchymal stem cells (MSCs) have the capacity to reverse acute and chronic lung injury in different experimental models through paracrine mechanisms. This paracrine action may be partially accounted for by MVs that are derived from MSCs. MSC-derived MVs may confer a stem cell-like phenotype to injured cells with the consequent activation of self-regenerative programmers. In this review, we summarize the characteristics and biological activities of MSC-derived MVs, and we describe their potential in novel therapeutic approaches in regenerative medicine to repair damaged tissues. Additionally, we provide an overview of studies that have assessed the role of MSC-derived MVs in lung diseases, including the mechanisms that may account for their therapeutic potential. Finally, we discuss the clinical use of MSC-derived MVs with several suggestions for enhancing their therapeutic efficiency.
    Full-text · Article · Jun 2015
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    • "Cell surface markers are key to identifying BMSCs [29] and our BMSCs preparations were positive for CD29, CD44, CD90, CD105, and negative for hematopoietic markers and endothelial markers such as CD14, CD34, CD45 and CD184. Immunofluorescence and flow cytometry confirmed that all cells from the four methods were positive for expressions of CD44 and negative for CD34, thus this confirmed BMSCs [30]–[32]. Data show that the four methods employed in the current investigation were not different with respect to cell purity. "
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    ABSTRACT: Bone marrow mesenchymal stem cells (BMSCs) have great potential in tissue engineering and clinical therapy, and various methods for isolation and cultivation of BMSCs have been reported. However, the best techniques are still uncertain. Therefore, we sought the most suitable among the four most common methods for BMSC separation from rabbits. BMSCs were obtained from untreated whole bone marrow (BM) adherent cultures, 3 volumes of red blood cells (RBC) lysed with ammonium chloride, 6 volumes of RBC lysed with ammonium chloride, and Ficoll density gradient centrifugation. Then, isolated BMSCs were evaluated with respect to primary cell yield, number of CFU-F colonies, proliferative capacity, cell phenotype, and chondrogenic differentiation potential. Our data show that BMSCs were successfully isolated by all four methods, and each method was similar with regard to cell morphology, phenotype, and differentiation potential. However, BMSCs from untreated whole BM adherent cultures had greater primary cell yields, larger colonies, and the shortest primary culture time (P<0.05). Moreover, the 4(th) generation of cultured cells had the strongest proliferative activity, the fastest growth rate and the most numerous cells compared with other cell passage generations (P<0.05). In conclusion, untreated whole BM adherent cultures are best for rabbit BMSC isolation and the 4(th) generation of cells has the strongest proliferation capacity.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "Mesenchymal stem cells (MSCs) are adult stem cells that possess unique immunomodulatory and paracrine properties, which make them attractive for cell based therapy [11]. Previous studies have demonstrated that MSCs had beneficial effects on experimental models of ALI in both animals [12], [13] and human tissue [14]. "
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    ABSTRACT: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality, and have no specific therapy. Keratinocyte growth factor (KGF) is a critical factor for pulmonary epithelial repair and acts via the stimulation of epithelial cell proliferation. Mesenchymal stem cells (MSCs) have been proved as good therapeutic vectors. Thus, we hypothesized that MSC-based KGF gene therapy would have beneficial effects on lipopolysaccharide(LPS)-induced lung injury. After two hours of intratracheal LPS administration to induce lung injury, mice received saline, MSCs alone, empty vector-engineered MSCs (MSCs-vec) or KGF-engineered MSCs (MSCs-kgf) via the tail vein. The MSCs-kgf could be detected in the recipient lungs and the level of KGF expression significantly increased in the MSCs-kgf mice. The MSC-mediated administration of KGF not only improved pulmonary microvascular permeability but also mediated a down-regulation of proinflammatory responses (reducing IL-1β and TNF-α) and an up-regulation of anti-inflammatory responses (increasing cytokine IL-10). Furthermore, the total severity scores of lung injury were significantly reduced in the MSCs-kgf group compared with the other three groups. The underlying mechanism of the protective effect of KGF on ALI may be attributed to the promotion of type II lung epithelial cell proliferation and the enhancement of surfactant synthesis. These findings suggest that MSCs-based KGF gene therapy may be a promising strategy for ALI treatment.
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