Effects of over-expression of SOD2 in bone marrow-derived mesenchymal stem cells on traumatic brain injury

Abstract

Intravenous administration of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been shown to promote nerve cell regeneration following traumatic brain injury (TBI). As the anti-oxidant defense systems in neuronal tissue including superoxide dismutase 2 (SOD2) are crucial to defend cell against oxidative stress. We proposed a new stratege to increase the therapeutic effect of MSCs by preventing cells death from oxidative stress. We overexpressed SOD2 in BM-MSCs, transplanted these MSCs into TBI model mice, assessed the protective effect of SOD2 against oxidation-induced apoptosis in BM-MSCs both in vitro and in vivo, evaluated brain functional recovery by the rotarod behavioral test, and tested the oxidation status of TBI mice brain after BM-MSCs transplantation by monitoring the superoxide dismutase, glutathione and malonaldehyde level. We found over-expression of SOD2 protected BM-MSCs from HO-induced cell apoptosis. Injection of SOD2 over-expressed BM-MSCs attenuated neuro-inflammation in the ipsilateral cortex of TBI mice, and protected TBI mice against loss of blood-brain barrier integrity. Furthermore, the rotarod behavioral test showed functional recovery of TBI mice after MSC treatment. Our experiments indicated that SOD2-over-expressed BM-MSCs have an improved therapeutic effect on brain injury treatment in TBI mice.

Evaluation of M2-like macrophage enrichment after diffuse traumatic brain injury through transient interleukin-4 expression from engineered mesenchymal stromal cells

“…Unfortunately, this corroborates many other attempts with genetically modified MSCs (49,63,65,67). Studies that saw an improvement typically saw a change in only one out of multiple assessments, or only looked at a single time point (63,64,66). In one study delivering recombinant IL-4 after stroke in IL-4 knockout mice, repeated measures were not accounted for and wild-type mice were not tested (52).…”

“…MSCs have previously been genetically altered to express desirable proteins. For rodent models of CNS injury, MSCs have been modified to overexpress bone-derived neurotrophic factor (BDNF) (63), superoxide dismutase 2 (SOD2) (64), interleukin-13 (IL-13) (65-67), or interleukin-10 (IL-10) (47,49). While most of these modifications have improved molecular parameters in each study, improved functional outcomes are only occasionally observed.…”

“…BDNF overexpression mildly improved outcomes in one functional SCI assessment (63). SOD2 overexpression demonstrated improved motor coordination at one timepoint tested after focal TBI (64). IL-13 overexpression promotes an M2-like phenotype, but it has only been observed to improve some functional assessments in an SCI model and failed to rescue function in stroke and epilepsy models (65)(66)(67).…”

Integrating the lncRNA and mRNA expression profiles of TLR4-primed mesenchymal stem cells in ankylosing spondylitis

“…SOD2 is a component of antioxidant defence systems, which are crucial in defending cells against oxidative stress. SOD2-overexpressing BM-MSCs have an enhanced therapeutic effect on brain injury treatment in traumatic brain injury mice [35]. Following exposure to systemic sclerosis patient serum, MSCs enhance the expression of the SOD2 antioxidant gene to adapt to the oxidative environment and exert their therapeutic effect [36].…”

Insights into superoxide dismutase 3 in regulating biological and functional properties of mesenchymal stem cells

“…Endotoxin found to protect MSCs and improve cell survival with increased proliferation under oxidative stress through upregulation of SOD2 [33]. Furthermore, overexpression of SOD2 in BM-MSCs found to increase its therapeutic potential in traumatic brain injury [34]. Recently, SOD3 is considered as a promising bio-compound for the treatment of several inflammatory diseases due to its ability to reduce inflammatory cascades by not only regulating oxidative stress but also by modulating various signaling pathways during inflammation.…”