Cu, Zn-Superoxide Dismutase Increases the Therapeutic Potential of Adipose-derived Mesenchymal Stem Cells by Maintaining Antioxidant Enzyme Levels

Abstract

In the present study, we investigated the ability of Cu, Zn-superoxide dismutase (SOD1) to improve the therapeutic potential of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) against ischemic damage in the spinal cord. Animals were divided into four groups: the control group, vehicle (PEP-1 peptide and artificial cerebrospinal fluid)-treated group, Ad-MSC alone group, and Ad-MSC-treated group with PEP-1-SOD1. The abdominal aorta of the rabbit was occluded for 30 min in the subrenal region to induce ischemic damage, and immediately after reperfusion, artificial cerebrospinal fluid or Ad-MSCs (2 × 10) were administered intrathecally. In addition, PEP-1 or 0.5 mg/kg PEP-1-SOD1 was administered intraperitoneally to the Ad-MSC-treated rabbits. Motor behaviors and NeuN-immunoreactive neurons were significantly decreased in the vehicle-treated group after ischemia/reperfusion. Administration of Ad-MSCs significantly ameliorated the changes in motor behavior and NeuN-immunoreactive neuronal survival. In addition, the combination of PEP-1-SOD1 and Ad-MSCs further increased the ameliorative effects of Ad-MSCs in the spinal cord after ischemia. Furthermore, the administration of Ad-MSCs with PEP-1-SOD1 decreased lipid peroxidation and maintained levels of antioxidants such as SOD1 and glutathione peroxidase compared to the Ad-MSC alone group. These results suggest that combination therapy using Ad-MSCs and PEP-1-SOD1 strongly protects neurons from ischemic damage by modulating the balance of lipid peroxidation and antioxidants.

Tat-protein disulfide-isomerase A3: a possible candidate for preventing ischemic damage in the spinal cord

“…For the assessment of neurological function, modified Tarlov criteria were used as follows: 29 0, no voluntary hind-limb function; 1, only perceptible joint movement; 2, active movement but unable to stand; 3, able to stand but unable to walk; or 4, completely normal hind-limb motor function. 4 , 12 , 46 , 47 All assessments were performed under blinded conditions to ensure objectivity, with two observers for each experiment. The assessments of control, PDIA3-treated, and Tat-PDIA3-treated groups were conducted under the same conditions.…”

“… 8 , 9 Several approaches to overcome neuronal damage in the spinal cord after ischemia/reperfusion have been attempted. 4 , 10 , 11 , 12 However, there are few comprehensive reports on the protein profile of spinal cord ischemia and the subsequent targeting of neuroprotective agents against this ischemic damage.…”

Influence of Bone Marrow-Derived Mesenchymal Stem Cell Therapy on Oxidative Stress Intensity in Minimally Conscious State Patients

“…On the other hand, it was documented that an excess of ROS negatively affected the neuroprotective potential of mesenchymal stem cell treatment. The adipose tissue-derived MSC (Ad-MSCs) treatment was less effective alone than in the case of the administration of Ad-MSCs with CuZn-SOD in a rabbit model of spinal cord ischemia [106]. Moreover, oxidative stress-induced impairments in cellular molecules promote stem cells aging [47] and reduce MSC survival [107]; however, the animal experimental model cannot be fully objective in relation to human therapy.…”

Reactive Oxygen Species, Superoxide Dimutases, and PTEN-p53-AKT-MDM2 Signaling Loop Network in Mesenchymal Stem/Stromal Cells Regulation

“…It has been shown SOD1-null animals develop some age-related diseases [ 31 ]. Amazingly, SOD1 may upturn the therapeutic potential of MSCs [ 32 ]. SOD2 is located in the mitochondrial matrix [ 33 ], which is the critical site of free radical production from the electron transportation chain.…”