Impact of the secretome of human mesenchymal stem cells on brain structure and animal behavior in a rat model of parkinson’s disease

Stem Cells Translational Medicine

Volumn 6, Issue 2, 2017, Pages 634-646

  Teixeira, Fábio G ^a,b   Carvalho, Miguel M ^a,b   Panchalingam, Krishna M ^c   Rodrigues, Ana J ^a,b   Mendes Pinheiro, Bárbara ^a,b   Anjo, Sandra ^d,e   Manadas, Bruno ^d,f   Behie, Leo A ^c   Sousa, Nuno ^a,b   Salgado, António J ^a,b  

^a UNIVERSITY OF MINHO   (Portugal)

^b UNIVERSITY OF MINHO   (Portugal)

^c UNIVERSITY OF CALGARY   (Canada)

^d UNIVERSITY OF COIMBRA   (Portugal)

^e UNIVERSITY OF COIMBRA   (Portugal)

^f Biocant Biotechnology Innovation Center   (Portugal)

Author keywords

Dopaminergic neurons; Mesenchymal stem cells; Neuroprotection; Parkinson s disease; Secretome

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; CYSTATIN C; GALECTIN 1; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; INTERLEUKIN 6; PIGMENT EPITHELIUM DERIVED FACTOR; PROTEASE NEXIN I; TYROSINE 3 MONOOXYGENASE; VASCULOTROPIN;

ANIMAL BEHAVIOR; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOMORPHINE TEST; ARTICLE; CELL SURVIVAL; CONTROLLED STUDY; CORPUS STRIATUM; DOPAMINERGIC NERVE CELL; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY; MALE; MESENCHYMAL STEM CELL TRANSPLANTATION; MICROCARRIER CULTURE; MOTOR COORDINATION; MOTOR PERFORMANCE; NERVOUS SYSTEM DEVELOPMENT; NEUROPROTECTION; NONHUMAN; PARKINSON DISEASE; PROTEOMICS; RAT; ROTAROD TEST; STAIRCASE TEST; STEM CELL EXPANSION; STEREOTAXIC SURGERY; STIRRED REACTOR; SUBSTANTIA NIGRA; ANIMAL; BRAIN; CELL CULTURE; DISEASE MODEL; MESENCHYMAL STEM CELL; METABOLISM; MOTOR ACTIVITY; PARACRINE SIGNALING; PARKINSONISM; PATHOLOGY; PATHOPHYSIOLOGY; PHENOTYPE; PROCEDURES; PSYCHOLOGY; SECRETORY PATHWAY; WISTAR RAT;

ANIMALS; BEHAVIOR, ANIMAL; BRAIN; CELLS, CULTURED; DISEASE MODELS, ANIMAL; DOPAMINERGIC NEURONS; HUMANS; MALE; MESENCHYMAL STEM CELL TRANSPLANTATION; MESENCHYMAL STEM CELLS; MOTOR ACTIVITY; NEUROGENESIS; PARACRINE COMMUNICATION; PARKINSONIAN DISORDERS; PHENOTYPE; PROTEOMICS; RATS, WISTAR; SECRETORY PATHWAY;

EID: 85017585369     PISSN: 21576564     EISSN: 21576580     Source Type: Journal    
DOI: 10.5966/sctm.2016-0071     Document Type: Article

References (75)

1. Carvalho MM, Campos FL, Coimbra B et al. Behavioral characterization of the 6-hydroxidopamine model of Parkinson’s disease and pharmacological rescuing of non-motor deficits. Mol Neurodegener 2013;8:14.
2. Lindvall O, Björklund A. Cell therapy in Parkinson’s disease. NeuroRx 2004;1:382–393.
3. Weiner WJ. Motor fluctuations in Parkinson’s disease. Rev Neurol Dis 2006;3: 101–108.
4. Miller RL, James-Kracke M, Sun GY et al. Oxidative and inflammatory pathways in Parkinson’s disease. Neurochem Res 2009;34:55–65.
5. Anisimov SV. Cell-based therapeutic approaches for Parkinson’s disease: Progress and perspectives. Rev Neurosci 2009;20: 347–381.
6. Singh N, Pillay V, Choonara YE. Advances in the treatment of Parkinson’s disease. Prog Neurobiol 2007;81:29–44.
7. Olanow CW, Lees A, Obeso J. Levodopa therapy for Parkinson’s disease: Challenges and future prospects. Mov Disord 2008;23 suppl 3:S495–S496.
8. Olanow CW. Levodopa/dopamine replacement strategies in Parkinson’s disease–future directions. Mov Disord 2008;23suppl 3: S613–S622.
9. Müller T, Hefter H, Hueber R et al. Is levodopatoxic? J Neurol 2004;251(suppl 6):VI/44–46.
10. Müller T, Renger K, Kuhn W. Levodopaassociated increase of homocysteine levels and sural axonal neurodegeneration. Arch Neurol 2004;61:657–660.
11. Weiner WJ. Advances in the diagnosis, treatment, and understanding of Parkinson’s disease and parkinsonism. Rev Neurol Dis 2006;3:191–194.
12. de la Fuente-Fernàndez R, Sossi V, Huang Z et al. Levodopa-induced changes in synaptic dopamine levels increase with progression of Parkinson’s disease: Implications for dyskinesias. Brain 2004;127:2747–2754.
13. Santini E, Valjent E, Fisone G. Parkinson’s disease: Levodopa-induced dyskinesia and signal transduction. FEBS J 2008;275:1392–1399.
14. Volkmann J. Update on surgery for Parkinson’s disease. Curr Opin Neurol 2007;20: 465–469
15. Altuğ F, Acar F, Acar G et al. The effects of brain stimulation of subthalamic nucleus surgery on gait and balance performance in Parkinson disease. A pilot study. Arch Med Sci 2014;10:733–738.
16. Castrioto A, Moro E. Newtargets for deep brain stimulation treatment of Parkinson’s disease. Expert Rev Neurother 2013;13:1319–1328.
17. Nordera GP, Mesiano T, Durisotti C et al. Six years’ experience in deep brain stimulation in Parkinson’s disease: Advantages and limitations of use of neurophysiological intraoperative microreading. Neurol Sci 2003;24:194.
18. Wang Y, Chen S, Yang D et al. Stem cell transplantation: A promising therapy for Parkinson’s disease. J Neuroimmune Pharmacol 2007;2:243–250.
19. Bouchez G, Sensebè L, Vourc’h P et al. Partial recovery of dopaminergic pathway after graft of adult mesenchymal stem cells in a rat model of Parkinson’s disease. Neurochem Int 2008;52:1332–1342.
20. Levy YS, Bahat-Stroomza M, Barzilay R et al. Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson’s disease. Cytotherapy 2008;10: 340–352.
21. Jin GZ, Cho SJ, Lee YS et al. Intrastriatal grafts of mesenchymal stem cells in adult intact rats can elevate tyrosine hydroxylase expression and dopamine levels. Cell Biol Int 2009; 34:135–140.
22. McCoy MK, Martinez TN, Ruhn KA et al. Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson’s disease. Exp Neurol 2008; 210:14–29.
23. Fu YS, Cheng YC, Lin MY et al. Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: Potential therapeutic application for Parkinsonism. STEM CELLS 2006;24: 115–124.
24. Venkataramana NK, Kumar SK, Balaraju S et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Transl Res 2010;155:62–70.
25. Drago D, Cossetti C, Iraci N et al. The stem cell secretome and its role in brain repair. Biochimie 2013;95:2271–2285.
26. Teixeira FG, Carvalho MM, Sousa N et al. Mesenchymal stem cells secretome: A new paradigm for central nervous system regeneration? Cell Mol Life Sci 2013;70: 3871–3882.
27. Paul G, Anisimov SV. The secretome of mesenchymal stem cells: Potential implications for neuroregeneration. Biochimie 2013;95: 2246–2256.
28. Cova L, Armentero MT, Zennaro E et al. Multiple neurogenic and neurorescue effects of human mesenchymal stem cell after transplantation in an experimental model of Parkinson’s disease. Brain Res 2010;1311: 12–27.
29. Wang F, Yasuhara T, Shingo T et al. Intravenous administration of mesenchymal stem cells exerts therapeutic effects on parkinsonian model of rats: Focusing on neuroprotective effects of stromal cell-derived factor-1alpha. BMC Neurosci 2010;11:52.
30. Weiss ML, Medicetty S, Bledsoe AR et al. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. STEM CELLS 2006;24:781–792.
31. Sadan O, Shemesh N, Cohen Y et al. Adult neurotrophic factor-secreting stem cells: A potential novel therapy for neurodegenerative diseases. Isr Med Assoc J 2009; 11:201–204.
32. Sadan O, Melamed E, Offen D. Bonemarrow-derived mesenchymal stem cell therapy for neurodegenerative diseases. Expert Opin Biol Ther 2009;9:1487–1497.
33. Sadan O, Bahat-Stromza M, Barhum Y et al. Protective effects of neurotrophic factorsecreting cells in a 6-OHDA rat model of Parkinson disease. Stem Cells Dev 2009;18: 1179–1190.
34. Teixeira FG, Carvalho MM, Neves-Carvalho A et al. Secretome of mesenchymal progenitors from the umbilical cord acts as modulator of neural/glial proliferation and differentiation. Stem Cell Rev 2015;11:288–297.
35. Teixeira FG, Panchalingam KM, Anjo SI et al. Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cell secretome? Stem Cell Res Ther 2015;6:133.
36. Paxinos G, Watson C. Rat Brain in Stereotaxic Coordinates. San Diego: Academic Press, 2004.
37. Boix J, Padel T, Paul G. Apartial lesionmodel of Parkinson’s disease in mice–characterization of a 6-OHDA-induced medial forebrain bundle lesion. Behav Brain Res 2015;284:196–206.
38. Thompson LH, Grealish S, Kirik D et al. Reconstruction of the nigrostriatal dopamine pathway in the adult mouse brain. Eur J Neurosci 2009;30:625–638.
39. Ramaswamy S, Soderstrom KE, Kordower JH. Trophic factors therapy in Parkinson’s disease. Prog Brain Res 2009;175:201–216.
40. Torres EM, Dowd E, Dunnett SB. Recovery of functional deficits following early donor age ventral mesencephalic grafts in a rat model of Parkinson’s disease. Neuroscience 2008;154: 631–640.
41. Monville C, Torres EM, Dunnett SB. Comparison of incremental and accelerating protocols of the rotarod test for the assessment of motor deficits in the 6-OHDA model. J Neurosci Methods 2006;158:219–223.
42. Campos FL, Carvalho MM, Cristovão AC et al. Rodent models of Parkinson’s disease: Beyond the motor symptomatology. Front Behav Neurosci 2013;7:175.
43. Montoya CP, Campbell-Hope LJ, Pemberton KD et al. The “staircase test”: A measure of independent forelimb reaching and grasping abilities in rats. J Neurosci Methods 1991; 36:219–228.
44. Bibbiani F, Costantini LC, Patel R et al. Continuous dopaminergic stimulation reduces risk of motor complications in parkinsonian primates. Exp Neurol 2005;192: 73–78.
45. Poewe W, Wenning GK. Apomorphine: An underutilized therapy for Parkinson’s disease. Mov Disord 2000;15:789–794.
46. Trenkwalder C, Chaudhuri KR, García Ruiz PJ et al. Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson’s disease–Clinical practice recommendations. Parkinsonism Relat Disord 2015; 21:1023–1030.
47. Febbraro F, Andersen KJ, Sanchez-Guajardo V et al. Chronic intranasal deferoxamine ameliorates motor defects and pathology in the a-synuclein rAAV Parkinson’s model. Exp Neurol 2013;247:45–58.
48. Anjo SI, Santa C, Manadas B. Short GeLCSWATH: A fast and reliable quantitative approach for proteomic screenings. Proteomics 2015;15:757–762.
49. Tang WH, Shilov IV, Seymour SL. Nonlinear fitting method for determining local false discovery rates from decoy database searches. J Proteome Res 2008;7:3661–3667.
50. Sennels L, Bukowski-Wills JC, Rappsilber J. Improved results in proteomics by use of local and peptide-class specific false discovery rates. BMC Bioinformatics 2009; 10:179.
51. Teixeira FG, Panchalingam KM, Assunção Silva R et al. Modulation of the mesenchymal stem cell secretome using computer-controlled bioreactors: Impact on neuronal cell proliferation, survival and differentiation. Sci Rep 2016; 6:27791.
52. Tabrez S, Jabir NR, Shakil S et al. A synopsis on the role of tyrosine hydroxylase in Parkinson’s disease. CNS Neurol Disord Drug Targets 2012;11:395–409.
53. Truong L, Allbutt H, Kassiou M et al. Developing a preclinicalmodel of Parkinson’s disease: A study of behaviour in rats with graded 6-OHDA lesions. Behav Brain Res 2006;169: 1–9.
54. Cerri S, Greco R, Levandis G et al. Intracarotid infusion of mesenchymal stem cells in an animal model of Parkinson’s disease, focusing on cell distribution and neuroprotective and behavioral effects. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1073–1085.
55. Allen SJ, Watson JJ, Shoemark DK et al. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol Ther 2013; 138:155–175.
56. Hirano T, Ishihara K, Hibi M. Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene 2000; 19:2548–2556.
57. Pucci S, Mazzarelli P, Missiroli F et al. Neuroprotection: VEGF, IL-6, and clusterin: The dark side of the moon. Prog Brain Res 2008;173:555–573.
58. Xiong N, Zhang Z, Huang J et al. VEGFexpressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson’s disease. Gene Ther 2011;18: 394–402.
59. Yasuhara T, Shingo T, Kobayashi K et al. Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson’s disease. Eur J Neurosci 2004;19:1494–1504.
60. Yasuhara T, Shingo T, Muraoka K et al. Neurorescue effects of VEGF on a rat model of Parkinson’s disease. Brain Res 2005;1053: 10–18.
61. Fujii H, Matsubara K, Sakai K et al. Dopaminergic differentiation of stem cells from human benefits for Parkinsonian rats. Brain Res 2015; 1613:59–72.
62. Stahl K, Mylonakou MN, Skare Ø et al. Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson’s disease. Brain Res 2011;1378:105–118.
63. Takeda M. [Intrathecal infusion of brainderived neurotrophic factor protects nigral dopaminergic neurons from degenerative changes in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridineinduced monkey parkinsonian model]. Hokkaido Igaku Zasshi 1995;70:829–838.
64. Baquet ZC, Bickford PC, Jones KR. Brain-derived neurotrophic factor is required for the establishment of the proper number of dopaminergic neurons in the substantia nigra pars compacta. J Neurosci 2005;25: 6251–6259.
65. Hoban DB, Howard L, Dowd E. GDNFsecreting mesenchymal stem cells provide localized neuroprotection in an inflammationdriven rat model of Parkinson’s disease. Neuroscience 2015;303:402–411.
66. Kirik D, Georgievska B, Björklund A. Localized striatal delivery of GDNF as a treatment for Parkinson disease. Nat Neurosci 2004;7:105–110.
67. d’Anglemont de, Tassigny X, Pascual A, L òpez-Barneo J. GDNF-based therapies, GDNFproducing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson’s disease. Front Neuroanat 2015;9:10.
68. Du Y, Li X, Yang D et al. Multiple molecular pathways are involved in the neuroprotection of GDNF against proteasome inhibitor induced dopamine neuron degeneration in vivo. Exp Biol Med (Maywood) 2008; 233:881–890.
69. Chao CC, Lee EH. Neuroprotective mechanism of glial cell line-derived neurotrophic factor on dopamine neurons: Role of antioxidation. Neuropharmacology 1999; 38:913–916.
70. D’Adamio L. Role of cystatin C in neuroprotection and its therapeutic implications. Am J Pathol 2010;177:2163–2165.
71. Hoffmann MC, Nitsch C, Scotti AL et al. The prolonged presence of glia-derived nexin, an endogenous protease inhibitor, in the hippocampus after ischemia-induced delayed neuronal death. Neuroscience 1992; 49:397–408.
72. Nonaka M, Fukuda M. Galectin-1 for neuroprotection? Immunity 2012;37:187–189.
73. Yabe T, Sanagi T, Yamada H. The neuroprotective role of PEDF: Implication for the therapy of neurological disorders. Curr Mol Med 2010;10:259–266.
74. Falk T, Gonzalez RT, Sherman SJ. The yin and yang of VEGF and PEDF: multifaceted neurotrophic factors and their potential in the treatment of Parkinson’s disease. Int J Mol Sci 2010;11:2875–2900.
75. Yasuda T, Fukuda-Tani M, Nihira T et al. Correlation between levels of pigment epithelium-derived factor and vascular endothelial growth factor in the striatum of patients with Parkinson’s disease. Exp Neurol 2007;206:308–317.