Avian precardiac endoderm/mesoderm induces cardiac myocyte differentiation in murine embryonic stem cells

Avian precardiac endoderm/mesoderm induces cardiac myocyte differentiation in murine embryonic stem cells
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DOI:
10.1161/01.res.0000134852.12783.6e
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发表时间:
2004-06-25
影响因子:
20.1
通讯作者:
Lough, J
Lough, J
中科院分区:
医学1区
文献类型:
--
作者:
Rudy-Reil, D;Lough, J

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胚胎干细胞(ES)组织再生受损心肌的能力目前正在进行广泛的调查。作为移植治疗的先决条件,必须制定策略,以诱导ES细胞的心脏表型。为此,胚胎诱导机制的线索已被利用,根据以前的研究结果,前外侧内胚层(心前内胚层)从原肠胚阶段的鸡胚有力地诱导心肌细胞分化的心前和nonprecardiac中胚层。假设禽类心前内胚层作为饲养/诱导细胞将诱导小鼠ES(mES)细胞向心肌细胞的高百分比转化,观察到大多数(约65%)共培养的ES细胞衍生的胚状体(EBs)富集在心肌细胞中并表现出节律性收缩。相比之下,单独培养的小鼠EB,或在小鼠胚胎成纤维细胞或禽类非心前后内胚层的饲养层上培养的小鼠EB,仅含有7%至16%的心肌细胞,同时表现出相对较低的发生率(
The ability to regenerate damaged myocardium with tissue derived from embryonic stem (ES) cells is currently undergoing extensive investigation. As a prerequisite to transplantation therapy, strategies must be developed to induce ES cells to the cardiac phenotype. Toward this end, cues from mechanisms of embryonic induction have been exploited, based on previous findings that anterior lateral endoderm (precardiac endoderm) from gastrulation-stage chick embryos potently induces cardiac myocyte differentiation in both precardiac and nonprecardiac mesoderm. Hypothesizing that avian precardiac endoderm acting as feeder/inducer cells would induce high percentage conversion of murine ES (mES) cells into cardiac myocytes, it was observed that the majority (approximate to 65%) of cocultured ES cell-derived embryoid bodies (EBs) were enriched in cardiac myocytes and exhibited rhythmic contractions. By contrast, mouse EBs cultured alone, or on feeder layers of mouse embryonic fibroblasts or avian nonprecardiac posterior endoderm, contained only 7% to 16% cardiac myocytes while exhibiting a relatively low incidence (