Mesenchymal Stem Cells as a Gene Delivery System to Create Biological Pacemaker Cells in vitro

被引:13
作者
Yang, X-J [1 ]
Zhou, Y. F. [1 ]
Li, H-X [1 ]
Han, L-H [1 ]
Jiang, W-P [1 ]
机构
[1] Soochow Univ, Dept Cardiol, Affiliated Hosp 1, Suzhou 215006, Jiangsu Prov, Peoples R China
关键词
MESENCHYMAL STEM CELLS; HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CHANNEL; PACEMAKER CELLS; LENTIVIRUS;
D O I
10.1177/147323000803600523
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Pacemaker cells differ from common cardiomyocytes due to the presence of a spontaneous depolarization process during the diastolic phase of the cardiac cycle. This is due to hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are responsible for providing an inward current. Genetically engineered mesenchymal stem cells (MSCs) were transfected with hHCN4 genes using lentiviral transfection, and their potential use as biological pacemaker cells was investigated. In addition to expressing an anticipated high level of the hHCN4 gene, MSCs transfected with hHCN4 genes also expressed characteristic hHCN4 protein, a cardiac pacemaker-like current and were capable of increasing the spontaneous beating rate of co-cultured cardiac myocytes. Control MSCs did not exert these effects. It is hypothesized that genetically engineered MSCs transfected with hHCN4 genes by lentiviral transfection can be modified to be cardiac pacemaker cells in vitro.
引用
收藏
页码:1049 / 1055
页数:7
相关论文
共 12 条
[1]   VOLTAGE-CLAMP INVESTIGATIONS OF MEMBRANE CURRENTS UNDERLYING PACE-MAKER ACTIVITY IN RABBIT SINO-ATRIAL NODE [J].
BROWN, H ;
DIFRANCESCO, D .
JOURNAL OF PHYSIOLOGY-LONDON, 1980, 308 (NOV) :331-351
[2]   Cesium and the pacemaker current [J].
DiFrancesco, D .
JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, 1995, 6 (12) :1152-1153
[3]   The heart rate-lowering agent ivabradine inhibits the pacemaker current If in human atrial myocytes [J].
El Chemaly, Antoun ;
Magaud, Christophe ;
Patri, Sylvie ;
Jayle, Christophe ;
Guinamard, Romain ;
Bois, Patrick .
JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, 2007, 18 (11) :1190-1196
[4]   Pathophysiology of HCN channels [J].
Herrmann, Stefan ;
Stieber, Juliane ;
Ludwig, Andreas .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2007, 454 (04) :517-522
[5]   Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep [J].
Liechty, KW ;
MacKenzie, TC ;
Shaaban, AF ;
Radu, A ;
Moseley, AB ;
Deans, R ;
Marshak, DR ;
Flake, AW .
NATURE MEDICINE, 2000, 6 (11) :1282-1286
[6]   Cardiomyocytes can be generated from marrow stromal cells in vitro [J].
Makino, S ;
Fukuda, K ;
Miyoshi, S ;
Konishi, F ;
Kodama, H ;
Pan, J ;
Sano, M ;
Takahashi, T ;
Hori, S ;
Abe, H ;
Hata, J ;
Umezawa, A ;
Ogawa, S .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 103 (05) :697-705
[7]   Multilineage potential of adult human mesenchymal stem cells [J].
Pittenger, MF ;
Mackay, AM ;
Beck, SC ;
Jaiswal, RK ;
Douglas, R ;
Mosca, JD ;
Moorman, MA ;
Simonetti, DW ;
Craig, S ;
Marshak, DR .
SCIENCE, 1999, 284 (5411) :143-147
[8]   Genes, stem cells and biological pacemakers [J].
Rosen, MR ;
Brink, PR ;
Cohen, IS ;
Robinson, RB .
CARDIOVASCULAR RESEARCH, 2004, 64 (01) :12-23
[9]  
Trono D, 2002, LENTIVIRAL VECTORS
[10]   Bioartificial sinus node constructed via in vivo gene transfer of an engineered pacemaker HCN channel reduces the dependence on electronic pacemaker in a sick-sinus syndrome model [J].
Tse, Hung-Fat ;
Xue, Tian ;
Lau, Chu-Pak ;
Siu, Chung-Wah ;
Wang, Kai ;
Zhang, Qing-Yong ;
Tomaselli, Gordon F. ;
Akar, Fadi G. ;
Li, Ronald A. .
CIRCULATION, 2006, 114 (10) :1000-1011