Therapeutic potential of porcine bronchoalveolar fluid‐derived mesenchymal stromal cells in a pig model of LPS‐induced ALI

Abstract

In this study, we isolated mesenchymal stromal (stem) cells (MSCs) from broncho-alveolar lavage fluid (BAL) of 2-6-week-old commercial pigs. BAL-MSCs displayed fibroblastic morphology and possessed self-renewal properties. Similar to bone-marrow MSCs, BAL-MSCs expressed mesenchymal markers and both cell types lacked the expression of hematopoetic markers. BAL-MSCs, when cultured in differentiation induction media, differentiated into adipocytes, osteocytes, and chondrocytes. Next, we examined if BAL-MSCs have the ability to treat lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a pig model. Five-week-old commercial pigs were inoculated intra-tracheally with E. coli LPS (1 mg/kg body weight [b.wt.]). Twelve hours after the LPS inoculation, groups of pigs were inoculated intra-tracheally with BM-MSCs or BAL-MSCs (2 × 10 cells/kg b.wt.). Forty eight hours after the cells administration pigs were euthanized and neutrophils in BAL, lung lesions, and cytokines in lung lysates, and engraftment of MSCs in lungs were examined. Engraftment of BAL-MSCs in injured lungs was significantly higher than the BM-MSCs, however, both cell types were equally effective in attenuating LPS-induced ALI as evidenced by decreased inflammation, lung lesions, and proinflammatory cytokines in the lungs of pigs treated with BAL- or BM-MSCs. These data in a preclinical large animal model suggest that BAL-MSCs may be used in clinical settings to treat ALI in humans.

Hydrogen-Rich Saline Inhibits Lipopolysaccharide-Induced Acute Lung Injury and Endothelial Dysfunction by Regulating Autophagy through mTOR/TFEB Signaling Pathway

“…LPS can cause severe pneumonia and sepsis and activate the downstream nuclear factor-kappa B (NF-κB) signaling pathway producing inflammatory mediators [7,8]. LPS was widely used in preparation of ALI animal models [9][10][11][12]. Among pulmonary cells, vascular endothelial cells (ECs) perform the important barrier between intravascular (IV) and extravascular (EV), which are always the primary target of inflammatory agents in local or systemic inflammation.…”

Lipopolysaccharide Inhibits Alpha Epithelial Sodium Channel Expression via MiR-124-5p in Alveolar Type 2 Epithelial Cells

“…Here, we aimed to investigate whether miR-124-5p has biologic impacts on the alveolar epithelium, which may exert effects on the pathophysiology of ALI. Mesenchymal stem cells (MSCs) are a subset of cells with a variety of differentiation potential and previous studies have shown the benefits of MSCs-based therapy in respiratory injury [14]. Cell-free MSCs-conditioned medium (MSCs-CM) therapy has been demonstrated to confer pulmonary ischemic tolerance by paracrine factors, and we hypothesized that the administration of MSCs-CM would attenuate ALI through changing the delivery of miR-124-5p into epithelial cells, which will lead to the alteration in the protein expression of ENaC [15].…”

Mesenchymal stem cells overexpressing heme oxygenase‐1 ameliorate lipopolysaccharide‐induced acute lung injury in rats

“…Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) with no effective treatment, are significant causes of morbidity and mortality in critically ill patients (Khatri & Richardson, 2018). Despite decades of tremendous research efforts, the mortality rate ranges from 22% to 40% (Xiang et al, 2017).…”