Cardiopoietic programming of embryonic stem cells for tumor-free heart repair.
Cardiopoietic programming of embryonic stem cells for tumor-free heart repair.
复制标题
DOI：
10.1084/jem.20061916
复制
发表时间：
2007-02-19
期刊：
影响因子：
--
通讯作者：
Terzic A
中科院分区：
文献类型：
--
作者：
Behfar A;Perez-Terzic C;Faustino RS;Arrell DK;Hodgson DM;Yamada S;Puceat M;Niederländer N;Alekseev AE;Zingman LV;Terzic A
胚胎干细胞具有明显的组织再生潜力，包括心脏修复。然而，它们的多谱系分化倾向带来了肿瘤生长的危险，阻碍了治疗应用。在这里，胚胎干细胞移植相关的致瘤性威胁被心脏限制性重编程细胞因子TNF-α的转基因表达所抑制，增强了受体心脏的成心能力。TNF-α在体内促进心脏分化的能力在体外胚状体中得到了再现。心原作用需要完整的内胚层，并由分泌的心感应信号介导。溶解的TNF-α -诱导的内胚层衍生因子，结合在鸡尾酒中，在单层胚胎干细胞中获得引导分化，产生心脏祖细胞，称为心肌细胞。以致癌标记下调、上调和心脏转录因子核易位为特征，这一预先确定的群体产生了功能性心肌细胞后代。在梗死心脏中注入的心肌细胞产生的心肌细胞增殖到疤痕组织中，与宿主心肌结合进行无肿瘤修复。因此，心脏生成编程建立了一种磨练干细胞多能性的策略，为再生提供了一种抗肿瘤的方法。
Embryonic stem cells have the distinct potential for tissue regeneration, including cardiac repair. Their propensity for multilineage differentiation carries, however, the liability of neoplastic growth, impeding therapeutic application. Here, the tumorigenic threat associated with embryonic stem cell transplantation was suppressed by cardiac-restricted transgenic expression of the reprogramming cytokine TNF-α, enhancing the cardiogenic competence of recipient heart. The in vivo aptitude of TNF-α to promote cardiac differentiation was recapitulated in embryoid bodies in vitro. The procardiogenic action required an intact endoderm and was mediated by secreted cardio-inductive signals. Resolved TNF-α–induced endoderm-derived factors, combined in a cocktail, secured guided differentiation of embryonic stem cells in monolayers produce cardiac progenitors termed cardiopoietic cells. Characterized by a down-regulation of oncogenic markers, up-regulation, and nuclear translocation of cardiac transcription factors, this predetermined population yielded functional cardiomyocyte progeny. Recruited cardiopoietic cells delivered in infarcted hearts generated cardiomyocytes that proliferated into scar tissue, integrating with host myocardium for tumor-free repair. Thus, cardiopoietic programming establishes a strategy to hone stem cell pluripotency, offering a tumor-resistant approach for regeneration.
登录
查看更多内容
影响因子：
3.3
作者：
Benus, GFJD;Wierenga, ATJ;Eggen, BJL
通讯作者：
Eggen, BJL
影响因子：
64.8
作者：
Anversa, P;Nadal-Ginard, B
通讯作者：
Nadal-Ginard, B
DOI：
10.1084/jem.20061469
发表时间：
2006-10-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolossov E;Bostani T;Roell W;Breitbach M;Pillekamp F;Nygren JM;Sasse P;Rubenchik O;Fries JW;Wenzel D;Geisen C;Xia Y;Lu Z;Duan Y;Kettenhofen R;Jovinge S;Bloch W;Bohlen H;Welz A;Hescheler J;Jacobsen SE;Fleischmann BK
通讯作者：
Fleischmann BK
影响因子：
37.8
作者：
Cao, F;Lin, S;Wu, JC
通讯作者：
Wu, JC
Notch 和 TGF-β 信号通路之间的串扰由 Notch 胞内结构域与 Smad3 的相互作用介导。
影响因子：
7.8
作者：
Blokzijl, A;Dahlqvist, C;Reissmann, E;Falk, A;Moliner, A;Lendahl, U;Ibáñez, CF
通讯作者：
Ibáñez, CF