title: Progenitor cells as remote "bioreactors": neuroprotection via modulation of the systemic inflammatory response.
abstract: Acute central nervous system (CNS) injuries such as spinal cord injury, traumatic brain injury, autoimmune encephalomyelitis, and ischemic stroke are associated with significant morbidity, mortality, and health care costs worldwide. Preliminary research has shown potential neuroprotection associated with adult tissue derived stem/progenitor cell based therapies. While initial research indicated that engraftment and transdifferentiation into neural cells could explain the observed benefit, the exact mechanism remains controversial. A second hypothesis details localized stem/progenitor cell engraftment with alteration of the loco-regional milieu; however, the limited rate of cell engraftment makes this theory less likely. There is a growing amount of preclinical data supporting the idea that, after intravenous injection, stem/progenitor cells interact with immunologic cells located in organ systems distant to the CNS, thereby altering the systemic immunologic/inflammatory response. Such distant cell "bioreactors" could modulate the observed post-injury pro-inflammatory environment and lead to neuroprotection. In this review, we discuss the current literature detailing the above mechanisms of action for adult stem/progenitor cell based therapies in the CNS.
authors: Peter A Walker, Phillip A Letourneau, Shinil K Shah, Charles S Cox Jr, Department of Surgery, University of Texas Medical School at Houston, Houston, TX 77030, United States.
authors: Peter A
authors: PA
authors: Walker
authors: Phillip A
authors: PA
authors: Letourneau
authors: Supinder
authors: S
authors: Bedi
authors: Shinil K
authors: SK
authors: Shah
authors: Fernando
authors: F
authors: Jimenez
authors: Charles S
authors: CS
authors: Cox
references: Stem Cells Dev. 2008 Oct;17(5):993-1003
references: 18537463
references: PLoS One. 2009;4(4):e5222
references: 19370156
references: Nature. 2006 Jun 29;441(7097):1075-9
references: 16810242
references: Stem Cells. 2006 Jun;24(6):1594-604
references: 16556707
references: Cell Mol Immunol. 2009 Jun;6(3):207-13
references: 19567204
references: Cell Transplant. 2009;18(12):1369-79
references: 19849895
references: Stem Cells Dev. 2009 Jun;18(5):683-92
references: 19099374
references: Methods Mol Biol. 2008;438:3-8
references: 18369744
references: Exp Neurol. 2006 May;199(1):191-200
references: 16713598
references: Acta Neurochir Suppl. 2006;99:133-6
references: 17370779
references: Annu Rev Immunol. 1993;11:165-90
references: 8386517
references: Stroke. 1996 Sep;27(9):1459-66
references: 8784113
references: Blood. 2005 Sep 1;106(5):1755-61
references: 15905186
references: Brain Res. 2008 May 7;1208:234-9
references: 18384759
references: J Trauma. 2007 Dec;63(6):1271-8
references: 18212649
references: Neuroreport. 2001 Mar 5;12(3):559-63
references: 11234763
references: Cell Transplant. 2002;11(3):275-81
references: 12075993
references: Stem Cells. 2006 Nov;24(11):2483-92
references: 16873764
references: Exp Neurol. 2007 Feb;203(2):542-54
references: 17078948
references: Surgery. 2008 Nov;144(5):803-13
references: 19081024
references: Science. 2002 Aug 23;297(5585):1299
references: 12193778
references: Acta Neurochir (Wien). 2005 Sep;147(9):985-92; discussion 992
references: 16010451
references: Science. 2002 Sep 27;297(5590):2256-9
references: 12215650
references: J Immunol. 2009 May 15;182(10):5994-6002
references: 19414750
references: Cell Stem Cell. 2009 Jul 2;5(1):54-63
references: 19570514
references: J Neurosurg. 2009 Jun;110(6):1189-97
references: 19301973
references: Blood. 2005 Feb 15;105(4):1815-22
references: 15494428
references: Arch Neurol. 2008 Jun;65(6):753-61
references: 18541795
references: J Neurotrauma. 2004 Jan;21(1):33-9
references: 14987463
references: Exp Neurol. 2002 Mar;174(1):11-20
references: 11869029
references: Exp Neurol. 2009 Jul;218(1):47-55
references: 19371742
references: J Neurosci Nurs. 2009 Jun;41(3):148-58
references: 19517765
references: Nucl Med Biol. 2010 Apr;37(3):381-8
references: 20346878
references: Stroke. 2008 Oct;39(10):2867-75
references: 18658037
references: Stem Cells Dev. 2010 Jun;19(6):867-76
references: 19775197
references: J Cereb Blood Flow Metab. 2009 Aug;29(8):1409-20
references: 19436312
references: Cell Transplant. 2008;17(7):865-73
references: 19044212
references: Brain. 2008 Mar;131(Pt 3):616-29
references: 18156155
references: PLoS Med. 2007 Sep;4(9):e269
references: 17803352
references: Nat Med. 2009 Jan;15(1):42-9
references: 19098906
references: Stem Cells Dev. 2006 Aug;15(4):583-94
references: 16978061
references: Nature. 2005 Jul 14;436(7048):266-71
references: 16015332
references: J Neurol Sci. 2009 Oct 15;285(1-2):67-77
references: 19555980
references: Am J Pathol. 2005 Dec;167(6):1647-60
references: 16314477
references: Brain Res. 2010 Jan 8;1306:149-58
references: 19799881
references: Stroke. 2010 Apr;41(4):739-44
references: 20150543
references: Am J Physiol. 1987 Sep;253(3 Pt 2):H699-703
references: 3631303