Neuroprotective effects of bone marrow-derived mesenchymal stem cells and conditioned medium in mechanically injured neuroblastoma cells

Neuroprotective effects of bone marrow-derived mesenchymal stem cells and conditioned medium in mechanically injured neuroblastoma cells

Background/aim: Bone marrow-derived mesenchymal stem cells (BMSCs) possess self-renewal characteristics that distinguish them from other cell types. Recent studies have focused on the effects of conditioned medium (CM) that includes the extracellular matrix. Here we examined the neuroprotective effects of BMSCs and CM on damaged neuroblastoma cells. Materials and methods: The cells were divided into five groups: 1) healthy controls, 2) damaged cells alone, 3) damaged cells treated with BMSCs, 4) damaged cells treated with CM, and 5) damaged cells treated with both BMSCs and CM. Neuroprotective effects were then evaluated based upon the levels of oxidative stress, antitransforming growth factor β1 (anti-TGFβ1) production, and apoptosis. Results: Significant differences were observed between healthy controls and damaged cells (P < 0.001), as well as between damaged cells and those treated with BMSCs alone (P < 0.05), CM alone (P < 0.05), and both BMSCs and CM in combination (P < 0.01). Among the treated groups, the strongest neuroprotective effects were seen in cells treated with both BMSCs and CM. Conclusion: These results show that both BMSCs and CM exhibit neuroprotective effects in damaged neuroblastoma cells. The strongest benefits were seen following treatment with both BMSCs and CM.

___

  • 1. Okolicsanyi RK, Griffiths LR, Haupt LM. Mesenchymal stem cells, neural lineage potential, heparan sulfate proteoglycans and the matrix. Dev Biol 2014; 1: 1-10.
  • 2. Hagmann S, Moradi B, Frank S, Dreher T, Kämmerer PW, Richter W, Gotterbarm T. Different culture media affect growth characteristics, surface marker distribution and chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells. BMC Musculoskelet Disord 2013; 14: 223.
  • 3. Sotiropoulou PA, Perez SA, Salagianni M, Baxevanis CN, Papamichail M. Characterization of the optimal culture conditions for clinical scale production of human mesenchymal stem cells. Stem Cells 2006; 24: 462-467.
  • 4. Uccelli A, Benvenuto F, Laroni A, Giunti D. Neuroprotective features of mesenchymal stem cells. Best Pract Res Clin Haematol 2011; 24: 59-64.
  • 5. Forostyak S, Jendelova P, Sykova E. The role of mesenchymal stromal cells in spinal cord injury, regenerative medicine and possible clinical applications. Biochimie 2013; 95: 2257-2270.
  • 6. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317.
  • 7. Dasari VR, Veeravalli KK, Dinh DH. Mesenchymal stem cells in the treatment of spinal cord injuries: a review. World J Stem Cells 2014; 26; 6: 120-133.
  • 8. Minguell JJ, Erices A, Conget P. Mesenchymal stem cells. Exp Biol Med (Maywood) 2001; 226: 507-520.
  • 9. Alexanian AR, Fehlings MG, Zhang Z, Maiman DJ. Transplanted neurally modified bone marrow-derived mesenchymal stem cells promote tissue protection and locomotor recovery in spinal cord injured rats. Neurorehabil Neural Repair 2011; 25: 873-880.
  • 10. Park JH, Kim DY, Sung IY, Choi GH, Jeon MH, Kim KK, Jeon SR. Long-term results of spinal cord injury therapy using mesenchymal stem cells derived from bone marrow in humans. Neurosurgery 2012; 70: 1238-1247.
  • 11. Shin DA, Kim JM, Kim HI, Yi S, Ha Y, Yoon do H, Kim KN. Comparison of functional and histological outcomes after intralesional, intracisternal, and intravenous transplantation of human bone marrow-derived mesenchymal stromal cells in a rat model of spinal cord injury. Acta Neurochir (Wien) 2013; 155: 1943-1950.
  • 12. Pavitan JA. Prospect of stem cell conditioned medium in regenerative medicine. Biomed Res Int 2014; 2014: 965849.
  • 13. Chang CP, Chio CC, Cheong CU, Chao CM, Cheng BC, Lin MT. Hypoxic preconditioning enhances the therapeutic potential of the secretome from cultured human mesenchymal stem cells in experimental traumatic brain injury. Clin Sci (Lond) 2013; 124: 165-176.
  • 14. Chuang TJ, Lin KC, Chio CC, Wang CC, Chang CP, Kuo JR. Effects of secretome obtained from normoxia-preconditioned human mesenchymal stem cells in traumatic brain injury rats. J Trauma Acute Care Surg 2012; 73: 1161-1167.
  • 15. Inoue T,  Sugiyama M,  Hattori H,  Wakita H,  Wakabayashi T,  Ueda M. Stem cells from human exfoliated deciduous tooth-derived conditioned medium enhance recovery of focal cerebral ischemia in rats. Tissue Eng Part A 2013; 19: 24-29.
  • 16. Bakondi B, Shimada IS, Perry A, Munoz JR, Ylostalo J, Howard AB,  Gregory CA,  Spees JL. CD133 identifies a human bone marrow stem/progenitor cell sub-population with a repertoire of secreted factors that protect against stroke. Mol Ther 2009; 17: 1938-1947.
  • 17. Cho YJ, Song HS, Bhang S, Lee S, Kang BG, Lee JC, An J, Cha CI, Nam DH, Kim BS, Joo KM. Therapeutic effects of human adipose stem cell-conditioned medium on stroke. J Neurosci Res 2012; 90: 1794-1802.
  • 18. Cantinieaux D,  Quertainmont R,  Blacher S,  Rossi L,  Wanet T,  Noël A,  Brook G,  Schoenen J,  Franzen R. Conditioned medium from bone marrow-derived mesenchymal stem cells improves recovery after spinal cord injury in rats: an original strategy to avoid cell transplantation. PLoS One 2013; 8: e69515.
  • 19. Tuğlu İ, Ozdal-Kurt F, Koca H, Saraç A, Barut T. The contribution of differentiated bone marrow stromal stem cellloaded biomaterial to treatment in critical size defect model in rats. Kafkas Üniv Vet Fak Derg 2010; 16: 783-792.
  • 20. Smith SL, Fishwick J, McLean WG, Edwards G, Ward SA. Enhanced in vitro neurotoxicity of artemisinin  derivatives  inthe  presence  of  haemin. Biochem. Pharmacol 1997; 10: 5-10.
  • 21. Vural K1, Tuğlu MI. Neurotoxic effect of statins on mouse neuroblastoma NB2a cell line. Eur Rev Med Pharmacol Sci 2011; 15: 985-991.
  • 22. Ma YH,  Zeng X,  Zhang K,  Zeng YS. A new in vitro injury model of Mouse neurons induced by mechanical scratching. Neurosci Lett 2012; 21: 14-19.
  • 23. Mete M, Aydemir I, Tuglu MI, Selcuki M. Neurotoxic effects of local anesthetics on the mouse neuroblastoma NB2a cell line. Biotech Histochem 2015; 90: 216-222.
  • 24. Huo DM, Dong FT, Yu WH, Gao F. Differentiation of mesenchymal stem cell in the microenvironment of retinitis pigmentosa. Int J Ophthalmol 2010; 3: 216-219.
  • 25. Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, Katakowski M, Zhang LJ, Lu M, Janakiraman N, Chopp M. Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology 2002; 27: 514-523.
  • 26. Tabe Y, Shi YX, Zeng Z, Jin L, Shikami M, Hatanaka Y, Miida T, Hsu FJ, Andreeff M, Konopleva M. TGF-β-neutralizing antibody 1D11 enhances cytarabine-induced apoptosis in AML cells in the bone marrow microenvironment. PLoS One 2013; 27: e62785. 
  • 27. Rozario T, DeSimone DW. The extracellular matrix in development and morphogenesis: a dynamic view. Dev Biol 2010; 1: 126-140.
  • 28. Li H, Fu X. Mechanisms of action of mesenchymal stem cells in cutaneous wound repair and regeneration. Cell Tissue Res 2012; 348: 371-377.
  • 29. Liang P, Liu J, Xiong J, Liu Q, Zhao J, Liang H, Zhao L, Tang H. Neural stem cell-conditioned medium protects neurons and promotes propriospinal neurons relay neural circuit reconnection after spinal cord injury. Cell Transplant 2014; 23: 45-56.
  • 30. Torrente D, Avila MF, Cabezas R, Morales L, Gonzalez J, Samudio I, Barreto GE. Paracrine factors of human mesenchymal stem cells increase wound closure and reduce reactive oxygen species production in a traumatic brain injury in vitro model. Hum Exp Toxicol 2014; 33: 673-684.
  • 31. Tate CC, Fonck C, McGrogan M, Case CC. Human mesenchymal stromal  cells  andtheir derivative,  SB623  cells, rescue neural cells via trophic support following in vitro ischemia. Cell Transplant 2010; 19: 973-984.