Mesoangioblasts from ventricular vessels can differentiate in vitro into cardiac myocytes with sinoatrial-like properties
Mesoangioblasts from ventricular vessels can differentiate in vitro into cardiac myocytes with sinoatrial-like properties
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DOI：
10.1016/j.yjmcc.2009.10.006
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发表时间：
2010-02-01
影响因子：
5
通讯作者：
DiFrancesco, Dario
中科院分区：
文献类型：
--
作者：
Barbuti, Andrea;Galvez, Beatriz G.;DiFrancesco, Dario
心脏成血管细胞（MAB）是一类血管相关的克隆形成，自我更新的祖细胞，最近在出生后的小鼠心脏中发现，并致力于心脏分化。在心脏发生过程中从祖细胞产生的心肌细胞获得几种不同的表型，对应于成年心脏不同结构中的不同功能特性。鉴于窦房细胞的节律产生和速率控制的特殊功能相关性，并鉴于其在治疗应用中的前瞻性用途，我们试图确定心脏成血管细胞是否也可以分化为具有成熟起搏肌细胞典型特性的肌细胞，以及在何种程度上。我们在这里报告，一个亚群的心脏mesoangioblast，诱导分化成心肌细胞在体外，获得一个表型与特定的成熟起搏器心肌细胞的属性。这些包括HCN 4亚型的起搏器（“有趣的”，f-）通道和连接蛋白45（Cx45）的表达，以及内向整流钾通道的表达减少。此外，MAB衍生的肌细胞形成起搏细胞的聚集体，显示稳定的节律活动，并且如在天然心脏起搏细胞中，通过自主递质的f通道调节有助于控制分化的中成血管细胞中的自发速率。这些数据代表了第一个证据，在体外产生的起搏器样肌细胞从增殖的非胚胎干/祖细胞。(C)2009爱思唯尔有限公司保留所有权利。
Cardiac mesoangioblasts (MABs) are a class of vessel-associated clonogenic, self-renewing progenitor cells, recently identified in the post-natal murine heart and committed to cardiac differentiation. Cardiomyocytes generated during cardiogenesis from Progenitor cells acquire several distinct phenotypes, corresponding to different functional properties in diverse structures of the adult heart. Given the special functional relevance to rhythm generation and rate control of sinoatrial cells, and in view of their prospective use in therapeutical applications, we sought to determine if, and to what extent, cardiac mesoangioblasts could also differentiate into myocytes with properties typical of mature pacemaker myocytes. We report here that a subpopulation of cardiac mesoangioblasts, induced to differentiate in vitro into cardiomyocytes, do acquire a phenotype with specific mature pacemaker myocytes properties. These include expression of the HCN4 isoform of pacemaker ("funny", f-) channels and connexin 45 (Cx45), as well as reduced expression of inwardly-rectifying potassium channels. Furthermore, MAB-derived myocytes form agglomerates of pacing cells displaying stable rhythmic activity, and as in native cardiac pacemaker cells, f-channel modulation by autonomic transmitters contributes to Control of spontaneous rate in differentiated mesoangioblasts. These data represent the first evidence for in vitro generation of pacemaker-like myocytes from proliferating non-embryonic stem/progenitor cells. (C) 2009 Elsevier Ltd. All rights reserved.