Cyclin D2 Overexpression Enhances the Efficacy of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Myocardial Repair in a Swine Model of Myocardial Infarction.
作者： Meng Zhao , Yuji Nakada , Yuhua Wei , Weihua Bian , Yuxin Chu
DOI: 10.1161/CIRCULATIONAHA.120.049497
关键词:
摘要: Background: Human-induced pluripotent stem cells (hiPSCs) with normal or upregulated levels of CCND2 expression were differentiated into cardiomyocytes (CCND2WTCMs CCND2OECMs, respectively) and injected infarcted pig hearts. Methods: Acute myocardial infarction (AMI) was induced via a 60-minute occlusion the left-anterior descending coronary artery. Immediately after reperfusion, CCND2WTCMs CCND2OECMs (3×107 each), an equivalent volume delivery vehicle around infarct border zone area. Results: The number engrafted exceeded that from 6 to 8-fold, rising 1 week 4 weeks post-implantation. In contrast treatment vehicle, administration CCND2OECM associated significantly improved left-ventricular function, as revealed by magnetic resonance imaging (MRI). This correlated reduction size, fibrosis, ventricular hypertrophy, CM apoptosis, increase vascular density arterial density, per histological analysis treated Expression cell proliferation markers (e.g., Ki67, phosphorylated histone 3 [PH3] Aurora Kinase B [Aurora B]) also in recipient CMs CCND2OECM-treated than CCND2WTCM-treated pigs. rate hypoxia tolerance measured cultured hiPSC-CMs greater their exosomes isolated (CCND2OEExos) (CCND2WTExos). As demonstrated our study, CCND2OEExos can promote activity postnatal rat adult mouse cardiomyocytes. A bulk miRNA sequencing vs. CCND2WTExos identified 206 91 miRNAs upand down-regulated, respectively. Gene ontology (GO) enrichment significant differences profiles various functional categories pathways, including implicated cell-cycle checkpoints (G2/M G1/S transitions), mechanism cytokinesis. Conclusions: We have enhanced potency promoted myocyte both grafts tissue large mammal acute model. These results suggest transplantation may be potential therapeutic strategy for repair
sci-hub.st 参考文章(36)
Wangde Dai, Loren E. Wold, Joan S. Dow, Robert A. Kloner, Thickening of the Infarcted Wall by Collagen Injection Improves Left Ventricular Function in Rats: A Novel Approach to Preserve Cardiac Function After Myocardial Infarction Journal of the American College of Cardiology. ,vol. 46, pp. 714- 719 ,(2005) , 10.1016/J.JACC.2005.04.056
Ichiro Shiojima, Kaori Sato, Yasuhiro Izumiya, Stephan Schiekofer, Masahiro Ito, Ronglih Liao, Wilson S Colucci, Kenneth Walsh, Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure Journal of Clinical Investigation. ,vol. 115, pp. 2108- 2118 ,(2005) , 10.1172/JCI24682
Wanjin Hong, Kun-Liang Guan, None, The YAP and TAZ transcription co-activators: Key downstream effectors of the mammalian Hippo pathway Seminars in Cell & Developmental Biology. ,vol. 23, pp. 785- 793 ,(2012) , 10.1016/J.SEMCDB.2012.05.004
S-Y Wen, Y Lin, Y-Q Yu, S-J Cao, R Zhang, X-M Yang, J Li, Y-L Zhang, Y-H Wang, M-Z Ma, W-W Sun, X-L Lou, J-H Wang, Y-C Teng, Z-G Zhang, miR-506 acts as a tumor suppressor by directly targeting the hedgehog pathway transcription factor Gli3 in human cervical cancer. Oncogene. ,vol. 34, pp. 717- 725 ,(2015) , 10.1038/ONC.2014.9
Shigeru Miyagawa, Yoshiki Sawa, Satoshi Taketani, Naomasa Kawaguchi, Toshikazu Nakamura, Nariaki Matsuura, Hikaru Matsuda, Myocardial Regeneration Therapy for Heart Failure Hepatocyte Growth Factor Enhances the Effect of Cellular Cardiomyoplasty Circulation. ,vol. 105, pp. 2556- 2561 ,(2002) , 10.1161/01.CIR.0000016722.37138.F2
Jason M. Duran, Sharven Taghavi, Remus M. Berretta, Catherine A. Makarewich, Thomas Sharp III, Tim Starosta, Foram Udeshi, Jon C. George, Hajime Kubo, Steven R. Houser, A characterization and targeting of the infarct border zone in a swine model of myocardial infarction. Clinical and Translational Science. ,vol. 5, pp. 416- 421 ,(2012) , 10.1111/J.1752-8062.2012.00432.X
Mingzhou Li, Youlin Xia, Yiren Gu, Kai Zhang, Qiulei Lang, Lei Chen, Jiuqiang Guan, Zonggang Luo, Haosi Chen, Yang Li, Qinghai Li, Xiang Li, An-an Jiang, Surong Shuai, Jinyong Wang, Qi Zhu, Xiaochuan Zhou, Xiaolian Gao, Xuewei Li, MicroRNAome of porcine pre- and postnatal development. PLOS ONE. ,vol. 5, ,(2010) , 10.1371/JOURNAL.PONE.0011541
H. C. Quevedo, K. E. Hatzistergos, B. N. Oskouei, G. S. Feigenbaum, J. E. Rodriguez, D. Valdes, P. M. Pattany, J. P. Zambrano, Q. Hu, I. McNiece, A. W. Heldman, J. M. Hare, Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity Proceedings of the National Academy of Sciences of the United States of America. ,vol. 106, pp. 14022- 14027 ,(2009) , 10.1073/PNAS.0903201106
Ana Eulalio, Miguel Mano, Matteo Dal Ferro, Lorena Zentilin, Gianfranco Sinagra, Serena Zacchigna, Mauro Giacca, None, Functional screening identifies miRNAs inducing cardiac regeneration Nature. ,vol. 492, pp. 376- 381 ,(2012) , 10.1038/NATURE11739
Hadi Valadi, Karin Ekström, Apostolos Bossios, Margareta Sjöstrand, James J Lee, Jan O Lötvall, Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells Nature Cell Biology. ,vol. 9, pp. 654- 659 ,(2007) , 10.1038/NCB1596