Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury

Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC) have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC) can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n=6) to intravenous oleic acid (OA) injury, ventilation and hMSC infusion, while the controls (n=5) had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1h after the administration of OA. The animals were monitored for additional 4h. Nuclear translocation of nuclear factor-light chain enhancer of activated B cells (NF-κB), a transcription factor that mediates several inflammatory pathways was reduced in hMSC treated pigs compared to controls (p=0.04). There was no significant difference in lung injury, assessed by histological scoring in hMSC treated pigs versus controls (p=0.063). There was no difference in neutrophil counts between hMSC-treated pigs and controls. Within 4h, there was no difference in the levels of IL-10 and IL-8 pre- and post-treatment with hMSC. In addition, there was no difference in hemodynamics, lung mechanics or arterial blood gases between hMSC treated animals and controls. Subsequent studies are required to determine if the observed decrease in inflammatory transcription factors will translate into improvement in inflammation and in physiological parameters over the long term.

Concise Review: Mesenchymal Stromal Cell-Based Approaches for the Treatment of Acute Respiratory Distress and Sepsis Syndromes

“…Large animal models including baboon, pig, and sheep have been developed for the study of ALI/ ARDS and these may more accurately represent various clinical facets of the human disease course. Indeed, encouraging results have been reported in porcine [85] and ovine [86] ALI/ARDS models regarding the effects of MSC treatment. However as preclinical research programs utilizing large animal models might take longer to complete, be more costly and require further specialized handling requirements, there usage is somewhat limited.…”

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

“…Investigating the transplantation of human MSCs in reducing induced-ALI by use of intravenous oleic acid in a pig model displayed that IL-8 elevation acts as a chemokine for neutrophil and is closely related to the intensity and duration of ALI. Therefore, there was a significant relationship between the neutrophil and the IL-8 concentration but a significant decrease in transcription of NF-κB inflammatory factor [37].…”

“…The MSCs migration also depends on transplantation route. Most studies have used intravenous route [30,[35][36][37][38][39] and a large portion of the MSCs is trapped in the lungs during the first pass [40]. Escape from the lung trap may improve the survival of the MSCs and affect cell distribution and its therapeutic effects after transplantation.…”

“…However, the available clinical data on the effects of the isolated MSCs from bone marrow is more than the other cells. The various reports indicate the efficacy of stem/stromal cell-based therapies in the significant reduction of the acute pulmonary inflammation induced by LPS in mice [28,30,47,48], rats [48][49][50], rabbit [5] and sheep [31], the pulmonary inflamma induced by oleic acid in rats [51] and pig [37], the lung inflammation caused by inhalation of smoke in sheep [36] and the inflammation of lung due to H9N2 avian influenza in mice [52] (Table 1).…”

Stem cells in lung repair and regeneration: Current applications and future promise

“…Mesenchymal stem cells are also a potential therapeutic for inflammatory diseases in other organs such as inflammatory bowel (Adak, Mukherjee, & Sen, 2017). (Li & Wu, 2015;Moodley et al, 2016). Moreover, administration of bone marrow or placental-derived MSCs has been successfully reduced both injury and inflammation in bacterially or endotoxin-injured human lung explants (Lee et al, 2013).…”