Cell and Tissue Research

, Volume 372, Issue 1, pp 67–75 | Cite as

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

Regular Article
First Online:
Received:
Accepted:

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 H2O2-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.

Keywords

Traumatic brain injury (TBI) Mesenchymal stem cell (MSC) Superoxide dismutase 2 (SOD2) Oxidative stress Antioxidant 
This is a preview of subscription content, log in to check access

Notes

Compliance with ethical standards

Disclosure of potential conflicts of interest

The authors declare that they have no conflict of interest.

Supplementary material

441_2017_2716_MOESM1_ESM.docx (361 kb)
ESM 1 (DOCX 361 kb)

References

  1. Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH (2008) Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes 57:1759–1767CrossRefPubMedPubMedCentralGoogle Scholar
  2. Barman A, Chatterjee A, Bhide R (2016) Cognitive impairment and rehabilitation strategies after traumatic brain injury. Indian J Psychol Med 38:172–181CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cornelius C, Crupi R, Calabrese V, Graziano A, Milone P, Pennisi G, Radak Z, Calabrese EJ, Cuzzocrea S (2013) Traumatic brain injury: oxidative stress and neuroprotection. Antioxid Redox Signal 19:836–853CrossRefPubMedGoogle Scholar
  4. Daneshvar DH, Riley DO, Nowinski CJ, McKee AC, Stern RA, Cantu RC (2011) Long-term consequences: effects on normal development profile after concussion. Phys Med Rehabil Clin N Am 22(683–700):ixGoogle Scholar
  5. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317CrossRefPubMedGoogle Scholar
  6. Drose S, Brandt U (2012) Molecular mechanisms of superoxide production by the mitochondrial respiratory chain. Adv Exp Med Biol 748:145–169CrossRefPubMedGoogle Scholar
  7. Gavioli M, Luppi G, Losi L, Bertolini F, Santantonio M, Falchi AM, D'Amico R, Conte PF, Natalini G (2005) Incidence and clinical impact of sterilized disease and minimal residual disease after preoperative radiochemotherapy for rectal cancer. Dis Colon Rectum 48:1851–1857CrossRefPubMedGoogle Scholar
  8. Hasan A, Deeb G, Rahal R, Atwi K, Mondello S, Marei HE, Gali A, Sleiman E (2017) Mesenchymal stem cells in the treatment of traumatic brain injury. Front Neurol 8:28CrossRefPubMedPubMedCentralGoogle Scholar
  9. Hyder AA, Wunderlich CA, Puvanachandra P, Gururaj G, Kobusingye OC (2007) The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation 22:341–353PubMedGoogle Scholar
  10. Hynes K, Bright R, Proudman S, Haynes D, Gronthos S, Bartold M (2016) Immunomodulatory properties of mesenchymal stem cell in experimental arthritis in rat and mouse models: a systematic review. Semin Arthritis Rheum 46:1–19CrossRefPubMedGoogle Scholar
  11. Ikebe C, Suzuki K (2014) Mesenchymal stem cells for regenerative therapy: optimization of cell preparation protocols. Biomed Res Int 2014:951512CrossRefPubMedPubMedCentralGoogle Scholar
  12. Lazarus HM, Winton EF, Williams SF, Grinblatt D, Campion M, Cooper BW, Gunn H, Manfreda S, Isaacs RE (1995) Phase I multicenter trial of interleukin 6 therapy after autologous bone marrow transplantation in advanced breast cancer. Bone Marrow Transplant 15:935–942PubMedGoogle Scholar
  13. Mahmood A, Lu D, Chopp M (2004) Intravenous administration of marrow stromal cells (MSCs) increases the expression of growth factors in rat brain after traumatic brain injury. J Neurotrauma 21:33–39CrossRefPubMedGoogle Scholar
  14. Meseguer-Olmo L, Montellano AJ, Martinez T, Martinez CM, Revilla-Nuin B, Roldan M, Mora CF, Lopez-Lucas MD, Fuente T (2017) Intraarticular and intravenous administration of 99MTc-HMPAO-labeled human mesenchymal stem cells (99MTC-AH-MSCS): in vivo imaging and biodistribution. Nucl Med Biol 46:36–42CrossRefPubMedGoogle Scholar
  15. Moghadasali R, Mutsaers HA, Azarnia M, Aghdami N, Baharvand H, Torensma R, Wilmer MJ, Masereeuw R (2013) Mesenchymal stem cell-conditioned medium accelerates regeneration of human renal proximal tubule epithelial cells after gentamicin toxicity. Exp Toxicol Pathol 65:595–600CrossRefPubMedGoogle Scholar
  16. Nargesi AA, Lerman LO, Eirin A (2017) Mesenchymal stem cell-derived extracellular vesicles for renal repair. Curr Gene Ther 17:29–42Google Scholar
  17. Peired AJ, Sisti A, Romagnani P (2016) Mesenchymal stem cell-based therapy for kidney disease: a review of clinical evidence. Stem Cells Int 2016:4798639PubMedPubMedCentralGoogle Scholar
  18. Rodriguez-Rodriguez A, Egea-Guerrero JJ, Murillo-Cabezas F, Carrillo-Vico A (2014) Oxidative stress in traumatic brain injury. Curr Med Chem 21:1201–1211CrossRefPubMedGoogle Scholar
  19. Rooney GE, Moran C, McMahon SS, Ritter T, Maenz M, Flugel A, Dockery P, O'Brien T, Howard L, Windebank AJ, Barry FP (2008) Gene-modified mesenchymal stem cells express functionally active nerve growth factor on an engineered poly lactic glycolic acid (PLGA) substrate. Tissue Eng Part A 14:681–690CrossRefPubMedGoogle Scholar
  20. Salehi H, Amirpour N, Razavi S, Esfandiari E, Zavar R (2017) Overview of retinal differentiation potential of mesenchymal stem cells: a promising approach for retinal cell therapy. Ann Anat 210:52–63CrossRefPubMedGoogle Scholar
  21. Sevivas N, Teixeira FG, Portugal R, Araujo L, Carrico LF, Ferreira N, Vieira da Silva M, Espregueira-Mendes J, Anjo S, Manadas B, Sousa N, Salgado AJ (2017) Mesenchymal Stem Cell Secretome: A Potential Tool for the Prevention of Muscle Degenerative Changes Associated With Chronic Rotator Cuff Tears. Am J Sports Med 45:179–188Google Scholar
  22. Thompson HJ, McCormick WC, Kagan SH (2006) Traumatic brain injury in older adults: epidemiology, outcomes, and future implications. J Am Geriatr Soc 54:1590–1595CrossRefPubMedPubMedCentralGoogle Scholar
  23. Tseng WL, Chou SJ, Chiang HC, Wang ML, Chien CS, Chen KH, Leu HB, Wang CY, Chang YL, Liu YY, Jong YJ, Lin SZ, Chiou SH, Lin SJ, Yu WC (2017) Imbalanced production of reactive oxygen species and mitochondrial antioxidant SOD2 in Fabry disease-specific human induced Pluripotent stem cell-differentiated vascular endothelial cells. Cell Transplant 26:513–527CrossRefPubMedPubMedCentralGoogle Scholar
  24. Uttara B, Singh AV, Zamboni P, Mahajan RT (2009) Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 7:65–74CrossRefPubMedPubMedCentralGoogle Scholar
  25. Wang S, Xu P, Li X, Su X, Chen Y, Wan L, Fan L, Yin K, Liu Y, Zhao RC (2016) Mesenchymal stem cells and cell therapy for bone repair. Curr Mol Pharmacol 9:289–299CrossRefPubMedGoogle Scholar
  26. Xu L, Emery JF, Ouyang YB, Voloboueva LA, Giffard RG (2010) Astrocyte targeted overexpression of Hsp72 or SOD2 reduces neuronal vulnerability to forebrain ischemia. Glia 58:1042–1049CrossRefPubMedPubMedCentralGoogle Scholar
  27. Yi HG, Yahng SA, Kim I, Lee JH, Min CK, Kim JH, Kim CS, Song SU (2016) Allogeneic clonal mesenchymal stem cell therapy for refractory graft-versus-host disease to standard treatment: a phase I study. Korean J Physiol Pharmacol 20:63–67CrossRefPubMedGoogle Scholar
  28. Yuan J, Wang A, He Y, Si Z, Xu S, Zhang S, Wang K, Wang D, Liu Y (2016) Cordycepin attenuates traumatic brain injury-induced impairments of blood-brain barrier integrity in rats. Brain Res Bull 127:171–176CrossRefPubMedGoogle Scholar
  29. Zhang X, Huang F, Chen Y, Qian X, Zheng SG (2016) Progress and prospect of mesenchymal stem cell-based therapy in atherosclerosis. Am J Transl Res 8:4017–4024PubMedPubMedCentralGoogle Scholar
  30. Zhang Z, Lang J, Cao Z, Li R, Wang X, Wang W (2017) Radiation-induced SOD2 overexpression sensitizes colorectal cancer to radiation while protecting normal tissue. Oncotarget 8:7791–7800PubMedGoogle Scholar
  31. Zhao Y, Gibb SL, Zhao J, Moore AN, Hylin MJ, Menge T, Xue H, Baimukanova G, Potter D, Johnson EM, Holcomb JB, Cox CS Jr, Dash PK, Pati S (2016) Wnt3a, a protein secreted by Mesenchymal stem cells is Neuroprotective and promotes Neurocognitive recovery following traumatic brain injury. Stem Cells 34:1263–1272CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Qilu HospitalJinanChina
  2. 2.Department of NeurosurgeryWeifang Yidu Central HospitalQingzhouChina

Personalised recommendations