Neurochemical Research

, Volume 41, Issue 12, pp 3300–3307 | Cite as

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

  • Dae Young Yoo
  • Dae Won Kim
  • Jin Young Chung
  • Hyo Young Jung
  • Jong Whi Kim
  • Yeo Sung Yoon
  • In Koo Hwang
  • Jung Hoon Choi
  • Goang-Min Choi
  • Soo Young Choi
  • Seung Myung Moon
Original Paper
First Online:
Received:
Revised:
Accepted:

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.

Keywords

Adipose tissue-derived mesenchymal stem cells Cu, Zn-superoxide dismutase Transient spinal cord ischemia Neuroprotection Antioxidants 
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Notes

Acknowledgments

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2014R1A1A2056492) and also supported by Priority Research Centers Program grant from the National Research Foundation (NRF-2009-0093812) funded by the Ministry of Science, ICT & Future Planning in the Republic of Korea.

Supplementary material

11064_2016_2062_MOESM1_ESM.tif (692 kb)
sFig. 1. Expression vector for PEP-1-SOD1 fusion protein. Construction of PEP-1-SOD1 expression vector system based on the vector pET-15b. Synthetic PEP-1 oligomer is cloned into the NdeІ, XhoІ sites, and SOD1 cDNA is cloned into the XhoІ, BamHІ sites of pET-15b. (TIF 692 KB)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Dae Young Yoo
    • 1
  • Dae Won Kim
    • 2
  • Jin Young Chung
    • 3
  • Hyo Young Jung
    • 1
  • Jong Whi Kim
    • 1
  • Yeo Sung Yoon
    • 1
  • In Koo Hwang
    • 1
  • Jung Hoon Choi
    • 4
  • Goang-Min Choi
    • 5
  • Soo Young Choi
    • 6
  • Seung Myung Moon
    • 7
  1. 1.Departments of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary ScienceSeoul National UniversitySeoulSouth Korea
  2. 2.Departments of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of DentistryGangneung-Wonju National UniversityGangneungSouth Korea
  3. 3.Departments of Veterinary Internal Medicine and Geriatrics, College of Veterinary Medicine and Institute of Veterinary ScienceKangwon National UniversityChuncheonSouth Korea
  4. 4.Department of Anatomy, College of Veterinary Medicine and Institute of Veterinary ScienceKangwon National UniversityChuncheonSouth Korea
  5. 5.Departments of Thoracic and Cardiovascular Surgery, Chuncheon Sacred Heart Hospital, College of MedicineHallym UniversityChuncheonSouth Korea
  6. 6.Department of Biomedical Sciences, and Research Institute for Bioscience and BiotechnologyHallym UniversityChuncheonSouth Korea
  7. 7.Department of Neurosurgery, Dongtan Sacred Heart Hospital, College of MedicineHallym UniversityHwaseongSouth Korea

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