title: Hepatocyte growth factor gene-modified bone marrow-derived mesenchymal stem cells transplantation promotes angiogenesis in a rat model of hindlimb ischemia.
abstract: Angiogenic gene therapy and cell-based therapy for peripheral arterial disease(PAD) have been studied intensively currently. This study aimed to investigate whether combining mesenchymal stem cells(MSCs) transplantation with ex vivo human hepatocyte growth factor(HGF) gene transfer was more therapeutically efficient than the MSCs therapy alone in a rat model of hindlimb ischemia. One week after establishing hindlimb ischemia models, Sprague-Dawley(SD) rats were randomized to receive HGF gene-modified MSCs transplantation(HGF-MSC group), untreated MSCs transplantation (MSC group), or PBS injection(PBS group), respectively. Three weeks after injection, angiogenesis was significantly induced by both MSCs and HGF-MSCs transplantation, and capillary density was the highest in the HGF-MSC group. The number of transplanted cell-derived endothelial cells was greater in HGF-MSC group than in MSC group after one week treatment. The expression of angiogenic cytokines such as HGF and VEGF in local ischemic muscles was more abundant in HGF-MSC group than in the other two groups. In vitro, the conditioned media obtained from HGF-MSCs cultures exerted proproliferative and promigratory effects on endothelial cells. It is concluded that HGF gene-modified MSCs transplantation therapy may induce more potent angiogenesis than the MSCs therapy alone. Engraftment of MSCs combined with angiogenic gene delivery may be a promising therapeutic strategy for the treatment of severe PAD.
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Su
authors.affiliation: Department of Cardiology, Wuhan Pu'ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China.
authors.forename: Yu-Fei
authors.initials: YF
authors.lastname: Sun
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. yongxin_lu6@yahoo.com.cn.
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Shuai
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Liao
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Qi-Yun
authors.initials: QY
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Wuhan Pu'ai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006614:Hindlimb / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000235:genetics*; D051381:Rats
chemical_list: D017228:Hepatocyte Growth Factor
references.citation: J Thorac Cardiovasc Surg. 2000 Nov;120(5):999-1005
references.pmid: 11044327
references.citation: Expert Opin Biol Ther. 2007 Jul;7(7):965-73
references.pmid: 17665987
references.citation: Plast Reconstr Surg. 2009 Feb;123(2 Suppl):45S-55S
references.pmid: 19182663
references.citation: Circulation. 1996 Dec 1;94(11):3026-49
references.pmid: 8941154
references.citation: In Vivo. 2009 Jan-Feb;23(1):21-7
references.pmid: 19368120
references.citation: Biochem Biophys Res Commun. 2009 Feb 20;379(4):1084-90
references.pmid: 19146824
references.citation: Circulation. 2004 Mar 30;109(12):1543-9
references.pmid: 15023891
references.citation: Stem Cells. 2004;22(3):405-14
references.pmid: 15153617
references.citation: Cell Biochem Funct. 2012 Oct;30(7):574-81
references.pmid: 22592978
references.citation: Am J Pathol. 2001 Mar;158(3):1111-20
references.pmid: 11238059
references.citation: Eur J Cardiothorac Surg. 2008 Oct;34(4):857-63
references.pmid: 18620865
references.citation: Stem Cells. 2007 Dec;25(12):3234-43
references.pmid: 17901400
references.citation: J Vasc Surg. 2000 Jan;31(1 Pt 2):S1-S296
references.pmid: 10666287
references.citation: Gene Ther. 2006 Nov;13(22):1564-8
references.pmid: 16810195
references.citation: J Cereb Blood Flow Metab. 2006 Sep;26(9):1176-88
references.pmid: 16421510
references.citation: J Virol. 1998 Nov;72(11):8463-71
references.pmid: 9765382
references.citation: Mol Ther. 2003 Sep;8(3):467-74
references.pmid: 12946320
references.citation: Cardiovasc Res. 2012 Sep 1;95(4):495-506
references.pmid: 22886775
references.citation: Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1168-73
references.pmid: 15831811
references.citation: Stem Cells. 2006 Jan;24(1):23-33
references.pmid: 16100005
references.citation: Circulation. 1998 Feb 3;97(4):381-90
references.pmid: 9468212
references.citation: Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):637-43
references.pmid: 18202326
references.citation: Cardiovasc Res. 2005 Jun 1;66(3):543-51
references.pmid: 15914119
references.citation: Gene Ther. 2000 Mar;7(5):417-27
references.pmid: 10694824
references.citation: Arch Med Res. 2008 Feb;39(2):179-88
references.pmid: 18164961
references.citation: J Autoimmun. 2008 May;30(3):121-7
references.pmid: 18249090
references.citation: Circ J. 2002 Dec;66(12):1077-86
references.pmid: 12499610
references.citation: Hypertension. 1996 Sep;28(3):409-13
references.pmid: 8794825
references.citation: Circ Res. 2004 Aug 20;95(4):354-63
references.pmid: 15321945
references.citation: Arch Intern Med. 2003 Apr 28;163(8):884-92
references.pmid: 12719196
references.citation: Hypertension. 1999 Jun;33(6):1379-84
references.pmid: 10373220
references.citation: Surg Today. 1996;26(4):236-41
references.pmid: 8727943
references.citation: Ann Thorac Surg. 2003 Jan;75(1):204-9
references.pmid: 12537217
references.citation: Vascul Pharmacol. 2006 Jun;44(6):395-405
references.pmid: 16698324
references.citation: J Cell Sci. 2005 Oct 1;118(Pt 19):4343-52
references.pmid: 16144866
references.citation: Transpl Int. 2008 Dec;21(12):1181-9
references.pmid: 18783386
references.citation: In Vivo. 2008 Sep-Oct;22(5):629-32
references.pmid: 18853759