title: 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 × 105) 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.
authors.affiliation: Departments of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.affiliation: Departments of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, 25457, South Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Departments of Veterinary Internal Medicine and Geriatrics, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Chung
authors.affiliation: Departments of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Hyo Young
authors.initials: HY
authors.lastname: Jung
authors.affiliation: Departments of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Jong Whi
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Departments of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.
authors.forename: Yeo Sung
authors.initials: YS
authors.lastname: Yoon
authors.affiliation: Departments of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Department of Anatomy, College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, 24341, South Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Departments of Thoracic and Cardiovascular Surgery, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon, 24253, South Korea.
authors.forename: Goang-Min
authors.initials: GM
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon, 24252, South Korea. sychoi@hallym.ac.kr.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Neurosurgery, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwaseong, 18450, South Korea. nsmsm@chol.com.
authors.forename: Seung Myung
authors.initials: SM
authors.lastname: Moon
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000201:enzymology / Q000523:psychology / Q000628:therapy*; D015227:Lipid Peroxidation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009043:Motor Activity; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000098:blood supply*; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C503924:Pep-1 peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D003543:Cysteamine; D005979:Glutathione Peroxidase; D000072105:Superoxide Dismutase-1
keywords: Adipose tissue-derived mesenchymal stem cells; Antioxidants; Cu, Zn-superoxide dismutase; Neuroprotection; Transient spinal cord ischemia