title: Bone marrow mononuclear cells exert long-term neuroprotection in a rat model of ischemic stroke by promoting arteriogenesis and angiogenesis.
abstract: Transplanted bone marrow-derived mononuclear cells (BMMNCs) can promote arteriogenesis and angiogenesis by incorporating into vascular walls and differentiating into smooth muscle cells (SMCs) and endothelial cells (ECs). Here, we explored whether BMMNCs can enhance arteriogenesis and angiogenesis and promote long-term functional recovery in a rat model of permanent middle cerebral artery occlusion (pMCAO). Sprague-Dawley rats were injected with vehicle or 1×10(7) BMMNCs labeled with BrdU via femoral vein 24 h after induction of pMCAO. Functional deficits were assessed weekly through day 42 after pMCAO, and infarct volume was assessed on day 7. We visualized the angioarchitecture by latex perfusion on days 14 and 42. BMMNC transplantation significantly reduced infarct volume and neurologic functional deficits compared with untreated or vehicle-treated ischemic groups. In BMMNC-treated rats, BrdU-positive cells were widely distributed in the infarct boundary zone, were incorporated into vessel walls, and enhanced the growth of leptomeningeal anastomoses, the circle of Willis, and basilar arteries. BMMNCs were shown to differentiate into SMCs and ECs from day 14 after stroke and preserved vascular repair function for at least 6 weeks. Our data indicate that BMMNCs can significantly enhance arteriogenesis and angiogenesis, reduce infarct volume, and promote long-term functional recovery after pMCAO in rats.
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China. Electronic address: wjpwfy666@126.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wang
authors.forename: Lie
authors.initials: L
authors.lastname: Yu
authors.forename: Chao
authors.initials: C
authors.lastname: Jiang
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Chunying
authors.initials: C
authors.lastname: Ou
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008297:Male; D018919:Neovascularization, Physiologic; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000473:pathology / Q000628:therapy*
keywords: Angiogenesis; Arteriogenesis; BMMNCs; Cerebral ischemia; Functional recovery; Infarct volume
references.citation: Stroke. 2010 Dec;41(12):2938-43
references.pmid: 20947840
references.citation: Stroke. 2011 Mar;42(3):770-5
references.pmid: 21257824
references.citation: PLoS One. 2012;7(3):e32793
references.pmid: 22412926
references.citation: Circ Res. 2004 Feb 6;94(2):230-8
references.pmid: 14656934
references.citation: Stroke. 2010 Sep;41(9):e552-60
references.pmid: 20671247
references.citation: Int J Stroke. 2012 Jun;7(4):309-10
references.pmid: 22583523
references.citation: Atherosclerosis. 2006 Aug;187(2):351-62
references.pmid: 16253262
references.citation: Circ Res. 2010 Jun 25;106(12):1870-81
references.pmid: 20431061
references.citation: Circulation. 2003 Oct 28;108(17):2070-3
references.pmid: 14568894
references.citation: PLoS One. 2011;6(6):e20673
references.pmid: 21677770
references.citation: Neuroscience. 2009 Mar 17;159(2):540-9
references.pmid: 19174184
references.citation: Stroke. 2011 Feb;42(2):453-8
references.pmid: 21164138
references.citation: Cell Transplant. 2011;20(10):1629-39
references.pmid: 22289660
references.citation: Circulation. 2010 May 11;121(18):2001-11
references.pmid: 20421519
references.citation: Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2128-34
references.pmid: 16051876
references.citation: J Neurosci Res. 2011 Jun;89(6):833-9
references.pmid: 21412816
references.citation: Ann Neurol. 2011 Jul;70(1):59-69
references.pmid: 21786299
references.citation: Stroke. 2009 Jan;40(1):254-60
references.pmid: 18927449
references.citation: J Clin Invest. 2008 Feb;118(2):505-14
references.pmid: 18172550
references.citation: BMC Neurosci. 2011 Jun 24;12:61
references.pmid: 21699735
references.citation: Circulation. 2011 Mar 1;123(8):866-76
references.pmid: 21321153
references.citation: Mol Ther. 2011 May;19(5):895-902
references.pmid: 21364544
references.citation: Circulation. 2010 Dec 7;122(23):2419-29
references.pmid: 21098445
references.citation: J Neurosci Res. 2010 Oct;88(13):2869-76
references.pmid: 20629187
references.citation: Lancet Neurol. 2011 Oct;10(10):909-21
references.pmid: 21939900
references.citation: Circulation. 2002 Sep 3;106(10):1199-204
references.pmid: 12208793
references.citation: PLoS One. 2010 Jul 23;5(7):e11746
references.pmid: 20668522
references.citation: J Cereb Blood Flow Metab. 2011 May;31(5):1243-50
references.pmid: 21102602
references.citation: Circulation. 2003 Aug 5;108(5):610-5
references.pmid: 12835229
references.citation: Nature. 2011 May 19;473(7347):298-307
references.pmid: 21593862
references.citation: Brain Res. 2009 Apr 17;1266:108-20
references.pmid: 19368806
references.citation: Stroke. 2001 Sep;32(9):2179-84
references.pmid: 11546914
references.citation: Diabetes Metab Res Rev. 2012 Feb;28 Suppl 1:27-9
references.pmid: 22271719
references.citation: Brain Res. 2004 May 8;1007(1-2):1-9
references.pmid: 15064130
references.citation: J Cereb Blood Flow Metab. 2003 May;23(5):621-8
references.pmid: 12771578
references.citation: Cell Transplant. 2001 Jan-Feb;10(1):31-40
references.pmid: 11294470
references.citation: Blood. 2011 May 5;117(18):4746-58
references.pmid: 21389315
references.citation: Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1526-31
references.pmid: 19759335
references.citation: Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1802-9
references.pmid: 19696399
references.citation: J Cereb Blood Flow Metab. 2010 Jan;30(1):140-9
references.pmid: 19773802
references.citation: Stroke. 2011 Mar;42(3):693-9
references.pmid: 21233472
references.citation: Circ Res. 2010 Nov 26;107(11):1355-63
references.pmid: 20930147
references.citation: Behav Brain Res. 2010 May 1;209(1):119-22
references.pmid: 20109497