Guided cardiopoiesis enhances therapeutic benefit of bone marrow human mesenchymal stem cells in chronic myocardial infarction.
Guided cardiopoiesis enhances therapeutic benefit of bone marrow human mesenchymal stem cells in chronic myocardial infarction.
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DOI：
10.1016/j.jacc.2010.03.066
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发表时间：
2010-08-24
影响因子：
24
通讯作者：
Terzic, Andre
中科院分区：
文献类型：
--
作者：
Behfar, Atta;Yamada, Satsuki;Crespo-Diaz, Ruben;Nesbitt, Jonathan J.;Rowe, Lois A.;Perez-Terzic, Carmen;Gaussin, Vinciane;Homsy, Christian;Bartunek, Jozef;Terzic, Andre
本研究的目的是引导骨髓来源的人间充质干细胞（hMSC）转化为心脏祖细胞表型，并评估慢性心肌梗死的治疗效果。在原始状态下输送的成体干细胞对缺血性心脏病患者的益处有限。先发制人的谱系预先指定可以优化治疗结果。 hMSC 是从冠状动脉疾病患者队列中采集的。配制由 TGFβ1、BMP-4、Activin-A、视黄酸、IGF-1、FGF-2、α-凝血酶和 IL-6 组成的重组混合物，使 hMSC 参与心脏生成。将衍生的 hMSC 注射到裸梗塞小鼠模型的心肌中，并跟踪 1 年多的功能和结构终点。虽然大多数源自患者的 hMSC 在其天然状态下对射血分数的影响有限，但来自罕见个体的干细胞具有改善收缩性能的自发能力。这种修复细胞型的特征是心脏生成标记物 Nkx2.5、Tbx5、Mesp-1 和 Mef2C 的高表达。重组心源鸡尾酒指导确保了整个患者群体的心脏生成表型。与无引导的对应物相比，递送至梗塞心肌的心脏生成 hMSC 实现了卓越的功能和结构益处，且没有不良副作用。植入小鼠心脏与增加人类特异性细胞核、肌节和间隙连接含量以及诱导心肌细胞周期活性相关。因此，引导心肌生成增强了骨髓来源的人间充质干细胞在慢性缺血性心肌病中的治疗效果。
The goal of this study was to guide bone marrow-derived human mesenchymal stem cells (hMSC) into a cardiac progenitor phenotype, and assess therapeutic benefit in chronic myocardial infarction. Adult stem cells, delivered in their naïve state, demonstrate a limited benefit in patients with ischemic heart disease. Preemptive lineage pre-specification may optimize therapeutic outcome. hMSC were harvested from a coronary artery disease patient cohort. A recombinant cocktail consisting of TGFβ1, BMP-4, Activin-A, retinoic acid, IGF-1, FGF-2, α-thrombin and IL-6 was formulated to engage hMSC into cardiopoiesis. Derived hMSC were injected into the myocardium of a nude infarcted murine model, and followed over 1-year for functional and structural end-points. While the majority of patient-derived hMSC in their native state demonstrated limited effect on ejection fraction, stem cells from rare individuals harbored a spontaneous capacity to improve contractile performance. This reparative cytotype was characterized by high expression of Nkx2.5, Tbx5, Mesp-1 and Mef2C, markers of cardiopoiesis. Recombinant cardiogenic cocktail guidance secured the cardiopoietic phenotype across the patient cohort. Compared to unguided counterparts, cardiopoietic hMSC delivered into infarcted myocardium achieved superior functional and structural benefit without adverse side effects. Engraftment into murine hearts was associated with increased human-specific nuclear, sarcomeric and gap junction content along with induction of myocardial cell cycle activity. Guided cardiopoiesis thus enhances the therapeutic benefit of bone marrow-derived human mesenchymal stem cells in chronic ischemic cardiomyopathy.
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DOI：
10.1084/jem.20061916
发表时间：
2007-02-19
期刊：
The Journal of experimental medicine
影响因子：
--
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
通讯作者：
Terzic A
影响因子：
5.2
作者：
Arrell, D. Kent;Niederlaender, Nicolas J.;Terzic, Andre
通讯作者：
Terzic, Andre
影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
通讯作者：
Sherman, Warren
影响因子：
37.8
作者：
Mummery, C;Ward-van Oostwaard, D;Tertoolen, L
通讯作者：
Tertoolen, L
影响因子：
24
作者：
Amado, Luciano C.;Schuleri, Karl H.;Hare, Joshua M.
通讯作者：
Hare, Joshua M.