Lasting Multiorgan Protective Effect of Stem Cells in Systemic Endotoxaemia

Stem cells exhibit protective properties in models of systemic endotoxaemia. This study aimed to explore whether stem cells could provide a sustained protective effect against oxidative stress, inflammation, and organ tissue damage in mice subjected to lipopolysaccharide (LPS) endotoxin. To achieve this, mice received an intraperitoneal (i.p.) injection of LPS (300 µg/kg) while simultaneously being treated with either saline or a suspension of bone marrow-derived stem cells (BM-SCs), followed by euthanasia 24 hours later. Results indicated that in comparison to the saline control, LPS administration led to (i) significant elevations in malondialdehyde (MDA) and nitric oxide (NO) levels in the brain and liver, alongside a notable reduction in reduced glutathione (GSH) and paraoxonase-1 (PON-1) activity; (ii) marked increases in serum concentrations of tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β); (iii) the presence of necrotic and apoptotic neurons, as well as perinuclear cytoplasmic vacuolations in the cerebral cortex and striatum; (iv) widespread necrosis of hepatocytes and apoptotic hepatocytes in the liver; (v) infiltration of mononuclear cells around the glomerulus and interstitial tubules, accompanied by tubular degeneration in the kidney; and (vi) pronounced caspase-3 immunostaining observed in the brain, liver, and kidney. In mice treated with LPS, bone marrow stem cells (BM-SCs) did not exhibit a significant impact on malondialdehyde (MDA) levels or nitric oxide in the brain or liver. However, there was a significant increase in brain glutathione (GSH) content and paraoxonase-1 (PON-1) activity in the BM-SCs-treated group compared to the LPS control group. Additionally, levels of TNF-α and IL-1β were significantly reduced. Stem cell therapy nearly mitigated the harmful effects of LPS on both the brain and liver, while also significantly alleviating kidney injury. Immunohistochemical analyses revealed a substantial decrease in caspase-3 immunoreactivity in the brain (specifically in the cortex and striatum), liver, and kidney tissues when compared to the LPS control group. Overall, these findings suggest that BM-SCs provide protection against tissue damage in organs during systemic endotoxemia, with this protective effect persisting, being evident 24 hours following stem cell therapy. The mechanisms underlying the protective effects of BM-SCs appear to involve anti-inflammatory and anti-apoptotic actions that inhibit the release of pro-inflammatory cytokines and the activation of caspase-3.