Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Comparison of Non-Coding RNAs in Exosomes and Functional Efficacy of Human Embryonic Stem Cell- versus Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
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DOI：
10.1002/stem.2669
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Wu JC
中科院分区：
文献类型：
--
作者：
Lee WH;Chen WY;Shao NY;Xiao D;Qin X;Baker N;Bae HR;Wei TT;Wang Y;Shukla P;Wu H;Kodo K;Ong SG;Wu JC
人胚胎干细胞衍生的心肌细胞（ESC-CM）和人诱导多能干细胞衍生的心肌细胞（iPSC-CM）都可以作为心脏再生治疗的无限细胞来源。然而，人类ESC-CM和iPSC-CM用于心脏再生治疗的功能等效性尚未得到证实。在这里，我们对ESC-CM和iPSC-CM在大鼠心肌梗死（MI）模型中恢复心脏功能的能力以及它们的外泌体分泌体进行了头对头比较。使用小分子抑制剂将人ESC和iPSC分化成心肌细胞。流式细胞术（FACS）分析证实，分别约85%和约83%的从ESC和iPSC分化的CM对心肌肌钙蛋白T呈阳性。在单细胞水平上，两种细胞类型显示出相似的钙处理和电生理特性，其基因表达与以横纹肌节为标志的人类胎儿心脏相当。心肌梗死后将ESC-CMs和iPSC-CMs亚急性移植到裸大鼠中改善了心脏功能，这与缺氧后体外血管生成基因表达增加有关。外泌体microRNA（miRs）和长链非编码RNA（lncRNA）的分析显示，两组都含有相同的miRs和lncRNA库，包括一些已知具有心脏保护作用的miRs和lncRNA。我们首次证明ESC-CM和iPSC-CM都可以促进可比的心脏修复。这是有利的，因为与治疗中使用的同种异体ESC-CM不同，自体iPSC-CM在将来用于心脏细胞移植时可能避免免疫排斥。人胚胎干细胞衍生的心肌细胞（ESC-CM）和人诱导多能干细胞衍生的心肌细胞（iPSC-CM）两者在移植到梗死心脏中后促进相当的功能恢复。外泌体分析揭示了来自ESC-CM和iPSC-CM的外泌体之间高度相似的microRNA和长非编码RNA含量，并且可能代表未来直接细胞治疗的替代方案。
Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can serve as unlimited cell sources for cardiac regenerative therapy. However, the functional equivalency between human ESC-CMs and iPSC-CMs for cardiac regenerative therapy has not been demonstrated. Here we performed a head-to-head comparison of ESC-CMs and iPSC-CMs in their ability to restore cardiac function in a rat myocardial infarction (MI) model as well as their exosomal secretome. Human ESCs and iPSCs were differentiated into cardiomyocytes using small molecule inhibitors. Fluorescence-activated cell sorting (FACS) analysis confirmed ~85% and ~83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable to the human fetal heart marked by striated sarcomeres. Sub-acute transplantation of ESC-CMs and iPSC-CMs into nude rats post-MI improved cardiac function, which was associated with increased expression of angiogenic genes in vitro following hypoxia. Profiling of exosomal microRNAs (miRs) and long non-coding RNAs (lncRNAs) revealed that both groups contain an identical repertoire of miRs and lncRNAs, including some that are known to be cardioprotective. We demonstrate for the first time that both ESC-CMs and iPSC-CMs can facilitate comparable cardiac repair. This is advantageous because unlike allogeneic ESC-CMs used in therapy, autologous iPSC-CMs could potentially avoid immune rejection when used for cardiac cell transplantation in the future. Both human embryonic stem cell-derived cardiomyocytes (ESC-CMs) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) facilitate comparable functional recovery following transplantation into infarcted hearts. Exosomal profiling revealed highly similar microRNA and long non-coding RNA contents between exosomes from ESC-CMs and iPSC-CMs and may represent an alternative to direct cell therapy in the future.
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影响因子：
37.8
作者：
Ong SG;Huber BC;Lee WH;Kodo K;Ebert AD;Ma Y;Nguyen PK;Diecke S;Chen WY;Wu JC
通讯作者：
Wu JC
影响因子：
64.8
作者：
Shiba, Yuji;Fernandes, Sarah;Zhu, Wei-Zhong;Filice, Dominic;Muskheli, Veronica;Kim, Jonathan;Palpant, Nathan J.;Gantz, Jay;Moyes, Kara White;Reinecke, Hans;Van Biber, Benjamin;Dardas, Todd;Mignone, John L.;Izawa, Atsushi;Hanna, Ramy;Viswanathan, Mohan;Gold, Joseph D.;Kotlikoff, Michael I.;Sarvazyan, Narine;Kay, Matthew W.;Murry, Charles E.;Laflamme, Michael A.
通讯作者：
Laflamme, Michael A.
影响因子：
48
作者：
Burridge, Paul W.;Matsa, Elena;Shukla, Praveen;Lin, Ziliang C.;Churko, Jared M.;Ebert, Antje D.;Lan, Feng;Diecke, Sebastian;Huber, Bruno;Mordwinkin, Nicholas M.;Plews, Jordan R.;Abilez, Oscar J.;Cui, Bianxiao;Gold, Joseph D.;Wu, Joseph C.
通讯作者：
Wu, Joseph C.
影响因子：
39.3
作者：
Menasche, Philippe;Vanneaux, Valerie;Larghero, Jerome
通讯作者：
Larghero, Jerome
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya