Treatment with bone marrow mesenchymal stem cells combined with plumbagin alleviates spinal cord injury by affecting oxidative stress, inflammation, apoptotis and the activation of the Nrf2 pathway

Abstract

The aim of the present study was to investigate the protective effect exerted by bone marrow mesenchymal stem cells (BMSCs) in combination with plumbagin on spinal cord injury (SCI) and explore the mechanism behind this protective effect. Firstly, BMSCs were extracted from male Sprague-Dawley rats, cultured in vitro, and identified by hematoxylin. Sprague-Dawley rats were then randomly divided into a control group, SCI model group, BMSC-treated group, a plumbagin-treated group, and a BMSC and plumbagin-treated group. After treatment with BMSCs combined with plumbagin, a Basso, Beattie and Bresnahan (BBB) test was carried out and the spinal cord water content was examined in order to analyze the effect of BMSCs combined with plumbagin on SCI. The myeloperoxidase (MPO), superoxide dismutase (SOD), malondialdehyde (MDA), nuclear factor-κB (NF-κB) p65 unit, tumor necrosis factor-α (TNF-α) levels were also detected. Moreover, nuclear factor erythroid 2‑related factor 2 (Nrf2), phosphoinositide 3-kinase (PI3K), phosphorylated (p-)Akt, p-p38 mitogen-activated protein kinase (MAPK), and p-extracellular-signal-regulated kinase (ERK) protein expression levels were measured using western blot analysis. Treatment with BMSCs combined with plumbagin significantly improved locomotor recovery and reduced the spinal cord water content after SCI. The increased MPO, MDA, NF-κB p65 and TNF-α levels were significantly suppressed and the decreased SOD was significantly increased in SCI rats. The suppression of Nrf2, p-Akt and p-ERK, as well as the promotion of p-p38 MAPK, were reversed by treatment with BMSCs combined with plumbagin. These effects suggest that treatment with BMSCs combined with plumbagin alleviates SCI through its effects on oxidative stress, inflammation, apoptotis and activation of the Nrf2 pathway.

Regulation of the mitochondrial reactive oxygen species: Strategies to control mesenchymal stem cell fates ex vivo and in vivo

“…As stem cell activities and differentiation capacities are important for MSC‐based therapeutic effects on repairing injury in vivo, drug treatments can also protect implanted MSCs from damage and then improve their biological activities for cell‐based treatments. The combination of bone marrow‐derived MSCs with plumbagin reduces the spinal cord water content after spinal cord injury by synergistically activating the Nrf2 pathway and regulating oxidative stress, inflammation and apoptosis in vivo . Injection of adipose‐derived MSCs and icariin markedly prevented apoptosis in transplanted MSCs and repaired erectile tissue structures in erectile dysfunction models, accompanied by increased levels of endothelial markers and smooth muscle markers in vivo …”

Coenzyme Q10 Regulation of Apoptosis and Oxidative Stress in H2O2 Induced BMSC Death by Modulating the Nrf-2/NQO-1 Signaling Pathway and Its Application in a Model of Spinal Cord Injury

“…Under treatment of SCI, some studies have shown that CoQ10 reduces the level of oxidative injury and antiapoptosis [19][20][21][22]. Medication combined with BMSC transplantation has been shown to have a powerful impact on protecting the vitality of cells and antioxidant and antiapoptotic compounds in SCI [23,24]. However, the method by which CoQ10 treatment can be combined with BMSC transplantation in SCI is still unclear.…”

Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells

“…4A and B). Since MSCs exert anti-inflammatory and immunomodulatory properties (30–32), we next explored whether VPA+S1P priming can influence the anti-inflammatory effect of UC-MSCs. To address this issue, we prepared the CM collected from UC-MSCs unprimed, primed by VPA or S1P alone, and primed by VPA+S1P and examined whether CM could suppress the secretion of TNF-α from MH-S cells, an alveolar macrophage cell line, by stimulation with LPS (3).…”