Therapeutic Potential of Mesenchymal Stromal Cells and MSC Conditioned Medium in Amyotrophic Lateral Sclerosis (ALS) - In Vitro Evidence from Primary Motor Neuron Cultures, NSC-34 Cells, Astrocytes and Microglia

PLoS ONE

Volumn 8, Issue 9, 2013, Pages

  Sun, Hui ^a,b   Bénardais, Karelle ^a,b   Stanslowsky, Nancy ^a,b   Thau Habermann, Nadine ^a,b   Hensel, Niko ^a,b   Huang, DongYa ^c   Claus, Peter ^a,b   Dengler, Reinhard ^a,b   Stangel, Martin ^a,b   Petri, Susanne ^a,b,d  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b CENTER FOR SYSTEMS NEUROSCIENCE   (Germany)

^c TONGJI UNIVERSITY   (China)

^d Integriertes Forschungs und Behandlungszentrum Transplantation   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CILIARY NEUROTROPHIC FACTOR; FRACTALKINE; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 6; STAUROSPORINE; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMAL CELL; ARTICLE; ASTROCYTE; CELL INTERACTION; CELL MUTANT; CELL PROTECTION; CELL STRAIN NSC 34; CELL THERAPY; CILIARY NEUROTROPHIC FACTOR GENE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CULTURE MEDIUM; EMBRYO; GENE EXPRESSION; IN VITRO STUDY; MESENCHYMAL STROMA CELL; MICROGLIA; MOTONEURON; MOUSE; NERVE CELL CULTURE; NERVE CELL NECROSIS; NEUROPROTECTION; NONHUMAN; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; UPREGULATION;

AMYOTROPHIC LATERAL SCLEROSIS; ANIMALS; APOPTOSIS; ASTROCYTES; CELLS, CULTURED; CHEMOKINE CX3CL1; CILIARY NEUROTROPHIC FACTOR; CULTURE MEDIA, CONDITIONED; GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTORS; HUMANS; MESENCHYMAL STROMAL CELLS; MICE; MICROGLIA; MOTOR NEURONS; STAUROSPORINE;

EID: 84884197667     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0072926     Document Type: Article

References (72)

1. Clement AM, (2003) Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice (vol 302, pg 113, 2003). Science 302: 568-568.
2. Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, et al. (2007) Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nature Neuroscience 10: 615-622.
3. Chen Y, Shao JZ, Xiang LX, Dong XJ, Zhang GR, (2008) Mesenchymal stem cells: a promising candidate in regenerative medicine. Int J Biochem Cell Biol 40: 815-820.
4. Garbuzova-Davis S, Willing AE, Saporta S, Bickford PC, Gemma C, et al. (2006) Novel cell therapy approaches for brain repair. Reprogramming the Brain 157: 207-222.
5. Woodbury D, Schwarz EJ, Prockop DJ, Black IB, (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61: 364-370.
6. Uccelli A, Pistoia V, Moretta L, (2007) Mesenchymal stem cells: a new strategy for immunosuppression? Trends Immunol 28: 219-226.
7. Isele NB, Lee HS, Landshamer S, Straube A, Padovan CS, et al. (2007) Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons. Neurochemistry International 50: 243-250.
8. Gu Y, Wang J, Ding F, Hu N, Wang Y, et al. (2010) Neurotrophic actions of bone marrow stromal cells on primary culture of dorsal root ganglion tissues and neurons. J Mol Neurosci 40: 332-341.
9. Vercelli A, Mereuta OM, Garbossa D, Muraca G, Mareschi K, et al. (2008) Human mesenchymal stem cell transplantation extends survival, improves motor performance and decreases neuroinflammation in mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 31: 395-405.
10. Uccelli A, Benvenuto F, Laroni A, Giunti D, (2011) Neuroprotective features of mesenchymal stem cells. Best Pract Res Clin Haematol 24: 59-64.
11. Zhao CP, Zhang C, Zhou SN, Xie YM, Wang YH, et al. (2007) Human mesenchymal stromal cells ameliorate the phenotype of SOD1-G93A ALS mice. Cytotherapy 9: 414-426.
12. Zhou C, Zhang C, Zhao R, Chi S, Ge P, (2013) Human marrow stromal cells reduce microglial activation to protect motor neurons in a transgenic mouse model of amyotrophic lateral sclerosis. J Neuroinflammation 10: 52.
13. Uccelli A, Milanese M, Principato MC, Morando S, Bonifacino T, et al. (2012) Intravenous mesenchymal stem cells improve survival and motor function in experimental amyotrophic lateral sclerosis. Mol Med 18: 794-804.
14. Mazzini L, Ferrero I, Luparello V, Rustichelli D, Gunetti M, et al. (2010) Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial. Exp Neurol 223: 229-237.
15. Mazzini L, Mareschi K, Ferrero I, Miglioretti M, Stecco A, et al. (2012) Mesenchymal stromal cell transplantation in amyotrophic lateral sclerosis: a long-term safety study. Cytotherapy 14: 56-60.
16. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, et al. (2010) Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 67: 1187-1194.
17. Cashman NR, Durham HD, Blusztajn JK, Oda K, Tabira T, et al. (1992) Neuroblastoma x spinal cord (NSC) hybrid cell lines resemble developing motor neurons. Dev Dyn 194: 209-221.
18. Ilieva H, Polymenidou M, Cleveland DW, (2009) Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol 187: 761-772.
19. Mattson MP, (2003) Excitotoxic and excitoprotective mechanisms- Abundant targets for the prevention and treatment of neurodegenerative disorders. Neuromolecular Medicine 3: 65-94.
20. Anderson CN, Tolkovsky AM, (1999) A role for MAPK/ERK in sympathetic neuron survival: protection against a p53-dependent, JNK-independent induction of apoptosis by cytosine arabinoside. J Neurosci 19: 664-673.
21. Brunet A, Datta SR, Greenberg ME, (2001) Transcription-dependent and-independent control of neuronal survival by the PI3K-Akt signaling pathway. Current Opinion in Neurobiology 11: 297-305.
22. Chopp M, Li Y, (2002) Treatment of neural injury with marrow stromal cells. Lancet Neurol 1: 92-100.
23. Iyer SS, Rojas M, (2008) Anti-inflammatory effects of mesenchymal stem cells: novel concept for future therapies. Expert Opin Biol Ther 8: 569-581.
24. Pastor D, Viso-Leon MC, Jones J, Jaramillo-Merchan J, Toledo-Aral JJ, et al. (2012) Comparative effects between bone marrow and mesenchymal stem cell transplantation in GDNF expression and motor function recovery in a motorneuron degenerative mouse model. Stem Cell Rev 8: 445-458.
25. Schafer S, Calas AG, Vergouts M, Hermans E, (2012) Immunomodulatory influence of bone marrow-derived mesenchymal stem cells on neuroinflammation in astrocyte cultures. J Neuroimmunol 249: 40-48.
26. Giess R, Holtmann B, Braga M, Grimm T, Muller-Myhsok B, et al. (2002) Early onset of severe familial amyotrophic lateral sclerosis with a SOD-1 mutation: Potential impact of CNTF as a candidate modifier gene. American Journal of Human Genetics 70: 1277-1286.
27. Li W, Brakefield D, Pan YC, Hunter D, Myckatyn TM, et al. (2007) Muscle-derived but not centrally derived transgene GDNF is neuroprotective in G93A-SOD1 mouse model of ALS. Experimental Neurology 203: 457-471.
28. Nagano I, Shiote M, Murakami T, Kamada H, Hamakawa Y, et al. (2005) Beneficial effects of intrathecal IGF-1 administration in patients with amyotrophic lateral sclerosis. Neurol Res 27: 768-772.
29. Thau N, Jungnickel J, Knippenberg S, Ratzka A, Dengler R, et al. (2012) Prolonged survival and milder impairment of motor function in the SOD1 ALS mouse model devoid of fibroblast growth factor 2. Neurobiol Dis 47: 248-257.
30. Wang Y, Mao XO, Xie L, Banwait S, Marti HH, et al. (2007) Vascular endothelial growth factor overexpression delays neurodegeneration and prolongs survival in amyotrophic lateral sclerosis mice. J Neurosci 27: 304-307.
31. Hirsch EC, Breidert T, Rousselet E, Hunot S, Hartmann A, et al. (2003) The role of glial reaction and inflammation in Parkinson's disease. Ann N Y Acad Sci 991: 214-228.
32. Rubio-Perez JM, Morillas-Ruiz JM, (2012) A review: inflammatory process in Alzheimer's disease, role of cytokines. ScientificWorldJournal 2012: 756357.
33. Poloni M, Facchetti D, Mai R, Micheli A, Agnoletti L, et al. (2000) Circulating levels of tumour necrosis factor-alpha and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis. Neurosci Lett 287: 211-214.
34. Chen K, Northington FJ, Martin LJ, (2010) Inducible nitric oxide synthase is present in motor neuron mitochondria and Schwann cells and contributes to disease mechanisms in ALS mice. Brain Structure & Function 214: 219-234.
35. Audet JN, Gowing G, Paradis R, Soucy G, Julien JP, (2012) Ablation of proliferating cells in the CNS exacerbates motor neuron disease caused by mutant superoxide dismutase. PLoS One 7: e34932.
36. Sekizawa T, Openshaw H, Ohbo K, Sugamura K, Itoyama Y, et al. (1998) Cerebrospinal fluid interleukin 6 in amyotrophic lateral sclerosis: immunological parameter and comparison with inflammatory and non-inflammatory central nervous system diseases. J Neurol Sci 154: 194-199.
37. Weydt P, Yuen EC, Ransom BR, Moller T, (2004) Increased cytotoxic potential of microglia from ALS-transgenic mice. Glia 48: 179-182.
38. Zhang R, Miller RG, Gascon R, Champion S, Katz J, et al. (2009) Circulating endotoxin and systemic immune activation in sporadic amyotrophic lateral sclerosis (sALS). J Neuroimmunol 206: 121-124.
39. Almer G, Vukosavic S, Romero N, Przedborski S, (1999) Inducible nitric oxide synthase up-regulation in a transgenic mouse model of familial amyotrophic lateral sclerosis. J Neurochem 72: 2415-2425.
40. Almer G, Guegan C, Teismann P, Naini A, Rosoklija G, et al. (2001) Increased expression of the pro-inflammatory enzyme cyclooxygenase-2 in amyotrophic lateral sclerosis. Ann Neurol 49: 176-185.
41. Phul RK, Shaw PJ, Ince PG, Smith ME, (2000) Expression of nitric oxide synthase isoforms in spinal cord in amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1: 259-267.
42. Kiaei M, Kipiani K, Petri S, Choi DK, Chen J, et al. (2005) Integrative role of cPLA with COX-2 and the effect of non-steriodal anti-inflammatory drugs in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem 93: 403-411.
43. Giunti D, Parodi B, Usai C, Vergani L, Casazza S, et al. (2012) Mesenchymal Stem Cells Shape Microglia Effector Functions Through the Release of CX3CL1. Stem Cells 30: 2044-2053.
44. Wiese S, Herrmann T, Drepper C, Jablonka S, Funk N, et al. (2010) Isolation and enrichment of embryonic mouse motoneurons from the lumbar spinal cord of individual mouse embryos. Nat Protoc 5: 31-38.
45. Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, et al. (1994) Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264: 1772-1775.
46. Ragancokova D, Jahn K, Kotsiari A, Schlesinger F, Haastert K, et al. (2009) Analysis of neuroprotective effects of valproic acid on primary motor neurons in monoculture or co-cultures with astrocytes or Schwann cells. Cell Mol Neurobiol 29: 1037-1043.
47. Sun H, Knippenberg S, Thau N, Ragancokova D, Korner S, et al. (2013) Therapeutic Potential of N-Acetyl-Glucagon-Like Peptide-1 in Primary Motor Neuron Cultures Derived From Non-Transgenic and SOD1-G93A ALS Mice. Cell Mol Neurobiol 33: 347-357.
48. Gao Q, Li Y, Chopp M, (2005) Bone marrow stromal cells increase astrocyte survival via upregulation of phosphoinositide 3-kinase/threonine protein kinase and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathways and stimulate astrocyte trophic factor gene expression after anaerobic insult. Neuroscience 136: 123-134.
49. Wierinckx A, Breve J, Mercier D, Schultzberg M, Drukarch B, et al. (2005) Detoxication enzyme inducers modify cytokine production in rat mixed glial cells. J Neuroimmunol 166: 132-143.
50. Soliman ML, Combs CK, Rosenberger TA, (2013) Modulation of inflammatory cytokines and mitogen-activated protein kinases by acetate in primary astrocytes. J Neuroimmune Pharmacol 8: 287-300.
51. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, et al. (2010) Safety and Immunological Effects of Mesenchymal Stem Cell Transplantation in Patients With Multiple Sclerosis and Amyotrophic Lateral Sclerosis. Archives of Neurology 67: 1187-1194.
52. Philpott KL, McCarthy MJ, Klippel A, Rubin LL, (1997) Activated phosphatidylinositol 3-kinase and Akt kinase promote survival of superior cervical neurons. J Cell Biol 139: 809-815.
53. Lambrechts D, Storkebaum E, Morimoto M, Del-Favero J, Desmet F, et al. (2003) VEGF is a modifier of amyotrophic lateral sclerosis in mice and humans and protects motoneurons against ischemic death. Nature Genetics 34: 383-394.
54. Kulshreshtha D, Vijayalakshmi K, Alladi PA, Sathyaprabha TN, Nalini A, et al. (2011) Vascular endothelial growth factor attenuates neurodegenerative changes in the NSC-34 motor neuron cell line induced by cerebrospinal fluid of sporadic amyotrophic lateral sclerosis patients. Neurodegener Dis 8: 322-330.
55. Pastor D, Viso-Len MC, Jones J, Jaramillo-Merchan J, Toledo-Aral JJ, et al. (2012) Comparative Effects between Bone Marrow and Mesenchymal Stem Cell Transplantation in GDNF Expression and Motor Function Recovery in a Motorneuron Degenerative Mouse Model. Stem Cell Reviews and Reports 8: 445-458.
56. Suzuki M, McHugh J, Tork C, Shelley B, Hayes A, et al. (2008) Direct muscle delivery of GDNF with human mesenchymal stem cells improves motor neuron survival and function in a rat model of familial ALS. Mol Ther 16: 2002-2010.
57. Pun S, Santos AF, Saxena S, Xu L, Caroni P, (2006) Selective vulnerability and pruning of phasic motoneuron axons in motoneuron disease alleviated by CNTF. Nature Neuroscience 9: 408-419.
58. Sun JJ, Liu Y, Ye ZR, (2008) Effects of P2Y1 receptor on glial fibrillary acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways. Neurosci Bull 24: 231-243.
59. Ugarte SD, Lin E, Klann E, Zigmond MJ, Perez RG, (2003) Effects of GDNF on 6-OHDA-induced death in a dopaminergic cell line: modulation by inhibitors of PI3 kinase and MEK. J Neurosci Res 73: 105-112.
60. Hiatt K, Lewis D, Shew M, Bijangi-Vishehsaraei K, Halum S (2012) Ciliary neurotrophic factor (CNTF) promotes skeletal muscle progenitor cell (MPC) viability via the phosphatidylinositol 3-kinase-Akt pathway. J Tissue Eng Regen Med.
61. Tovar YRLB, Tapia R, (2010) VEGF protects spinal motor neurons against chronic excitotoxic degeneration in vivo by activation of PI3-K pathway and inhibition of p38MAPK. J Neurochem 115: 1090-1101.
62. Boucherie C, Schafer S, Lavand'homme P, Maloteaux JM, Hermans E, (2009) Chimerization of astroglial population in the lumbar spinal cord after mesenchymal stem cell transplantation prolongs survival in a rat model of amyotrophic lateral sclerosis. J Neurosci Res 87: 2034-2046.
63. Choi MR, Kim HY, Park JY, Lee TY, Baik CS, et al. (2010) Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis. Neurosci Lett 472: 94-98.
64. Delarosa O, Dalemans W, Lombardo E, (2012) Mesenchymal stem cells as therapeutic agents of inflammatory and autoimmune diseases. Curr Opin Biotechnol 23: 978-983.
65. Salem HK, Thiemermann C, (2010) Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28: 585-596.
66. Morganti JM, Nash KR, Grimmig BA, Ranjit S, Small B, et al. (2012) The Soluble Isoform of CX3CL1 Is Necessary for Neuroprotection in a Mouse Model of Parkinson's Disease. Journal of Neuroscience 32: 14592-14601.
67. Lee S, Varvel NH, Konerth ME, Xu G, Cardona AE, et al. (2010) CX3CR1 deficiency alters microglial activation and reduces beta-amyloid deposition in two Alzheimer's disease mouse models. Am J Pathol 177: 2549-2562.
68. Cho SH, Sun BG, Zhou YG, Kauppinen TM, Halabisky B, et al. (2011) CX3CR1 Protein Signaling Modulates Microglial Activation and Protects against Plaque-independent Cognitive Deficits in a Mouse Model of Alzheimer Disease. Journal of Biological Chemistry 286: 32713-32722.
69. Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, et al. (2006) Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci 9: 917-924.
70. Mizuno T, Kawanokuchi J, Numata K, Suzumura A, (2003) Production and neuroprotective functions of fractalkine in the central nervous system. Brain Res 979: 65-70.
71. Meucci O, Fatatis A, Simen AA, Bushell TJ, Gray PW, et al. (1998) Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci U S A 95: 14500-14505.
72. Shi M, Bradner J, Hancock AM, Chung KA, Quinn JF, et al. (2011) Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol 69: 570-580.