Manganese-Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri-Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia-Reperfusion Model

被引:17
作者
Dash, Rajesh [1 ,3 ]
Kim, Paul J. [1 ]
Matsuura, Yuka [1 ]
Ikeno, Fumiaki [1 ]
Metzler, Scott [1 ]
Huang, Ngan F. [1 ,3 ]
Lyons, Jennifer K. [1 ]
Nguyen, Patricia K. [1 ,3 ]
Ge, Xiaohu [1 ]
Foo, Cheryl Wong Po [5 ]
McConnell, Michael V. [1 ,2 ,3 ]
Wu, Joseph C. [1 ,3 ]
Yeung, Alan C. [1 ]
Harnish, Phillip [4 ]
Yang, Phillip C. [1 ,3 ]
机构
[1] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA
[3] Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA
[4] Eagle Vis Pharmaceut Corp, Downingtown, PA USA
[5] Biocardia Inc, San Carlos, CA USA
来源
JOURNAL OF THE AMERICAN HEART ASSOCIATION | 2015年 / 4卷 / 07期
基金
美国国家卫生研究院;
关键词
ischemia-reperfusion injury; magnetic resonance imaging; manganese-enhanced magnetic resonance imaging; peri-infarct region imaging; stem cell imaging; BONE-MARROW; CONTRAST AGENT; HEART-FAILURE; BORDER ZONE; CARDIOMYOPATHY; SAFETY; VIABILITY; INJECTION; INJURY; MRI;
D O I
10.1161/JAHA.115.002044
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri-infarct region (PIR) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese-enhanced magnetic resonance imaging [MEMRI]), myocardial scar (delayed gadolinium enhancement MRI), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts. Methods and Results-Twelve adult swine underwent ischemia-reperfusion injury. Digital subtraction of MEMRI-negative myocardium (intrainfarct region) from delayed gadolinium enhancement MRI-positive myocardium (PIR and intrainfarct region) clearly delineated the PIR in which the MEMRI-positive signal reflected PIR viability. Human amniotic mesenchymal stem cells (hAMSCs) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine PIR. Immediately following hAMSC delivery, MEMRI demonstrated an increased PIR viability signal compared with control. Direct PIR viability remained higher in hAMSC-treated hearts for > 6 weeks. Increased PIR viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and hAMSC engraftment, as confirmed by immunocytochemistry. Increased MEMRI and positron emission tomography reporter gene signal in the intrainfarct region and the PIR correlated with sustained functional augmentation (global and regional) within the hAMSC group (mean change, left ventricular ejection fraction: hAMSC 85 +/- 60%, control 8 +/- 10%; P<0.05) and reduced chamber dilatation (left ventricular end-diastole volume increase: hAMSC 24 +/- 8%, control 110 +/- 30%; P<0.05). Conclusions-The positron emission tomography reporter gene signal of hAMSC engraftment correlates with the improved MEMRI signal in the PIR. The increased MEMRI signal represents PIR viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real-time method of tracking PIR viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells.
引用
收藏
页数:15
相关论文
共 27 条
[1]   Dual Manganese-Enhanced and Delayed Gadolinium-Enhanced MRI Detects Myocardial Border Zone Injury in a Pig Ischemia-Reperfusion Model [J].
Dash, Rajesh ;
Chung, Jaehoon ;
Ikeno, Fumiaki ;
Hahn-Windgassen, Annett ;
Matsuura, Yuka ;
Bennett, Mihoko V. ;
Lyons, Jennifer K. ;
Teramoto, Tomohiko ;
Robbins, Robert C. ;
McConnell, Michael V. ;
Yeung, Alan C. ;
Brinton, Todd J. ;
Harnish, Phillip P. ;
Yang, Phillip C. .
CIRCULATION-CARDIOVASCULAR IMAGING, 2011, 4 (05) :574-582
[2]   Transendocardial autologous bone marrow in myocardial infarction induced heart failure, two-year follow-up in an open-label phase I safety study (the TABMMI study) [J].
de la Fuente, Luis M. ;
Stertzer, Simon H. ;
Argentieri, Julio ;
Penaloza, Eduardo ;
Koziner, Benjamin ;
Rouy, Didier ;
Altman, Peter A. .
EUROINTERVENTION, 2011, 7 (07) :805-812
[3]   Human Amniotic Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells May Generate a Universal Source of Cardiac Cells [J].
Ge, Xiaohu ;
Wang, I-Ning E. ;
Toma, Ildiko ;
Sebastiano, Vittorio ;
Liu, Jianwei ;
Butte, Manish J. ;
Pera, Renee A. Reijo ;
Yang, Phillip C. .
STEM CELLS AND DEVELOPMENT, 2012, 21 (15) :2798-2808
[4]   Quantitative Tissue Characterization of Infarct Core and Border Zone in Patients With Ischemic Cardiomyopathy by Magnetic Resonance Is Associated With Future Cardiovascular Events [J].
Heidary, Shahriar ;
Patel, Harendra ;
Chung, Jaehoon ;
Yokota, Hajime ;
Gupta, Sandeep N. ;
Bennett, Mihoko V. ;
Katikireddy, Chandra ;
Nguyen, Patricia ;
Pauly, John M. ;
Terashima, Masahiro ;
McConnell, Michael V. ;
Yang, Phillip C. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2010, 55 (24) :2762-2768
[5]   Multimodal evaluation of in vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells [J].
Hendry, Stephen L., II ;
van der Bogt, Koen E. A. ;
Sheikh, Ahmad Y. ;
Arai, Takayasu ;
Dylla, Scott J. ;
Drukker, Micha ;
McConnell, Michael V. ;
Kutschka, Ingo ;
Hoyt, Grant ;
Cao, Feng ;
Weissman, Irving L. ;
Connolly, Andrew J. ;
Pelletier, Marc P. ;
Wu, Joseph C. ;
Robbins, Robert C. ;
Yang, Phillip C. .
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, 2008, 136 (04) :1028-U14
[6]   Multimodality Evaluation of the Viability of Stem Cells Delivered Into Different Zones of Myocardial Infarction [J].
Hung, Ta-Chuan ;
Suzuki, Yoriyasu ;
Urashima, Takashi ;
Caffarelli, Anthony ;
Hoyt, Grant ;
Sheikh, Ahmad Y. ;
Yeung, Alan C. ;
Weissman, Irving ;
Robbins, Robert C. ;
Bulte, Jeff W. ;
Yang, Phillip C. .
CIRCULATION-CARDIOVASCULAR IMAGING, 2008, 1 (01) :6-13
[7]   Hypoxia-preconditioned mesenchymal stromal cells improve cardiac function in a swine model of chronic myocardial ischaemia [J].
Jaussaud, Jeremie ;
Biais, Matthieu ;
Calderon, Joachim ;
Chevaleyre, Jean ;
Duchez, Pascale ;
Ivanovic, Zoran ;
Couffinhal, Thierry ;
Barandon, Laurent .
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, 2013, 43 (05) :1050-1057
[8]   Preserved coronary endothelial function by inhibition of δ protein kinase C in a porcine acute myocardial infarction model [J].
Kaneda, Hideaki ;
Ikeno, Fumiaki ;
Inagaki, Koichi ;
Mochly-Rosen, Daria .
INTERNATIONAL JOURNAL OF CARDIOLOGY, 2009, 133 (02) :256-259
[9]   Feasibility, Safety, and Therapeutic Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Sheets in a Porcine Ischemic Cardiomyopathy Model [J].
Kawamura, Masashi ;
Miyagawa, Shigeru ;
Miki, Kenji ;
Saito, Atsuhiro ;
Fukushima, Satsuki ;
Higuchi, Takahiro ;
Kawamura, Takuji ;
Kuratani, Toru ;
Daimon, Takashi ;
Shimizu, Tatsuya ;
Okano, Teruo ;
Sawa, Yoshiki .
CIRCULATION, 2012, 126 (11) :S29-+
[10]  
Kim J, 2007, CELL PROLIFERAT, V40, P75