title: Fusion between human mesenchymal stem cells and rodent cerebellar Purkinje cells.
abstract: OBJECTIVE
  we explored whether cellular fusion and heterokaryon formation between human and rodent cells in the cerebellum of mice occurs after intravenous injection of human bone marrow-derived mesenchymal stem cells (MSCs). The influence of central nervous system inflammation on this process was also assessed. In addition, we examined whether tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, factors associated with inflammation, increase cellular fusion between human MSCs and rodent cerebellar neurons in vitro.
  
  
  RESULTS
  human MSCs were intravenously injected into mice with experimental autoimmune encephalomyelitis (EAE) and control mice. After 22 days, mouse Purkinje cells expressing human Golgi Zone were found within the Purkinje cell layer of the cerebellum, indicating that fusion and heterokaryon formation had occurred. The numbers of heterokaryons in the cerebellum were markedly increased in mice with EAE compared with control mice. Rodent cerebellar neuronal cells labelled with enhanced green fluorescent proteinin vitro were co-cultured with human bone marrow-derived MSCs in the presence of TNF-alpha and/or IFN-gamma to determine their influence on fusion events. We found that fusion between MSCs and cerebellar neurons did occur in vitro and that the frequency of cellular fusion increased in the presence of TNF-alpha and/or IFN-gamma.
  
  
  CONCLUSIONS
  we believe that this is the first paper to define fusion and heterokaryon formation between human MSCs and rodent cerebellar neurons in vivo. We have also demonstrated that fusion between these cell populations occurs in vitro. These findings indicate that MSCs may be potential therapeutic agents for cerebellar diseases, and other neuroinflammatory and neurodegenerative disorders.
authors.affiliation: Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, UK. kevin.kemp@bristol.ac.uk
authors.forename: K
authors.initials: K
authors.lastname: Kemp
authors.forename: D
authors.initials: D
authors.lastname: Gordon
authors.forename: D C
authors.initials: DC
authors.lastname: Wraith
authors.forename: E
authors.initials: E
authors.lastname: Mallam
authors.forename: E
authors.initials: E
authors.lastname: Hartfield
authors.forename: J
authors.initials: J
authors.lastname: Uney
authors.forename: A
authors.initials: A
authors.lastname: Wilkins
authors.forename: N
authors.initials: N
authors.lastname: Scolding
mesh_terms: D000818:Animals; D002459:Cell Fusion / Q000379:methods*; D004681:Encephalomyelitis, Autoimmune, Experimental; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011689:Purkinje Cells / Q000166:cytology*
references.citation: J Neurosci. 1988 Dec;8(12):4780-9
references.pmid: 3199205
references.citation: Blood. 2001 Jan 15;97(2):435-41
references.pmid: 11154220
references.citation: Ann Neurol. 2005 Jun;57(6):874-82
references.pmid: 15929052
references.citation: J Neural Transm Suppl. 2000;59:81-9
references.pmid: 10961421
references.citation: Bone Marrow Transplant. 2004 Mar;33(6):597-604
references.pmid: 14716336
references.citation: J Cell Biol. 2001 Nov 26;155(5):733-8
references.pmid: 11724815
references.citation: J Immunol. 2000 Jan 1;164(1):419-26
references.pmid: 10605038
references.citation: Neurosurgery. 2005 Nov;57(5):1026-31; discussion 1026-31
references.pmid: 16284572
references.citation: Nat Cell Biol. 2008 May;10(5):503-5
references.pmid: 18454127
references.citation: Cytotherapy. 2006;8(4):315-7
references.pmid: 16923606
references.citation: Lancet Neurol. 2002 Jun;1(2):92-100
references.pmid: 12849513
references.citation: J Interferon Cytokine Res. 1998 Jun;18(6):415-21
references.pmid: 9660249
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11474-9
references.pmid: 16061805
references.citation: J Neurochem. 2010 Sep;114(6):1569-80
references.pmid: 20028455
references.citation: J Neurosci. 2007 Sep 12;27(37):9885-92
references.pmid: 17855603
references.citation: Neurosurgery. 2003 Sep;53(3):697-702; discussion 702-3
references.pmid: 12943585
references.citation: Science. 1968 Jan 19;159(3812):310-2
references.pmid: 5634498
references.citation: Nat Cell Biol. 2008 May;10(5):575-83
references.pmid: 18425116
references.citation: Hum Gene Ther. 2005 Aug;16(8):1006-11
references.pmid: 16076258
references.citation: Nat Cell Biol. 2003 Nov;5(11):952-4
references.pmid: 14593417
references.citation: Nat Cell Biol. 2003 Nov;5(11):959-66
references.pmid: 14562057
references.citation: Exp Hematol. 2002 Jan;30(1):42-8
references.pmid: 11823036
references.citation: Science. 1999 Apr 2;284(5411):143-7
references.pmid: 10102814
references.citation: J Neurol Sci. 2008 Feb 15;265(1-2):111-5
references.pmid: 17904159
references.citation: Clin Pharmacol Ther. 2008 May;83(5):723-30
references.pmid: 17898702
references.citation: J Neurosci Res. 2006 Aug 15;84(3):587-95
references.pmid: 16773650
references.citation: Brain Res. 2004 Dec 24;1030(1):19-27
references.pmid: 15567334
references.citation: Nat Cell Biol. 2008 May;10(5):584-92
references.pmid: 18425115
references.citation: Exp Hematol. 2003 Oct;31(10):890-6
references.pmid: 14550804
references.citation: Neurorehabil Neural Repair. 2006 Jun;20(2):278-96
references.pmid: 16679505
references.citation: Brain Res. 1973 Apr 27;53(2):273-89
references.pmid: 4735887
references.citation: Immunol Lett. 2007 Jun 15;110(2):91-100
references.pmid: 17507101
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2088-93
references.pmid: 12576546
references.citation: Blood. 2003 Apr 15;101(8):2999-3001
references.pmid: 12480709
references.citation: Neurosci Lett. 2008 Dec 19;448(1):71-3
references.pmid: 18950680
references.citation: Stem Cells. 2007 May;25(5):1307-16
references.pmid: 17470534
references.citation: Lancet. 2004 Jul 10-16;364(9429):193-9
references.pmid: 15246733
references.citation: Blood. 2005 Mar 1;105(5):2214-9
references.pmid: 15514012
references.citation: Nature. 2002 Oct 3;419(6906):437
references.pmid: 12374136
references.citation: J Neuroimmunol. 2006 Sep;178(1-2):1-8
references.pmid: 16872684
references.citation: Exp Hematol. 2001 Feb;29(2):244-55
references.pmid: 11166464
references.citation: Bone Marrow Transplant. 2007 Oct;40(7):609-19
references.pmid: 17603514