Hemodynamic Stimulation Using the Biomimetic Cardiac Tissue Model (BCTM) Enhances Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Hemodynamic Stimulation Using the Biomimetic Cardiac Tissue Model (BCTM) Enhances Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
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DOI：
10.1159/000496934
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Sethu P
中科院分区：
文献类型：
--
作者：
Rogers AJ;Kannappan R;Abukhalifeh H;Ghazal M;Miller JM;El-Baz A;Fast VG;Sethu P
人诱导多能干细胞(HiPSC)来源的心肌细胞(hiPSC-CMS)在心血管疾病模型和再生医学中具有广阔的应用前景。然而，HiPSC-CMS在结构和功能上都不成熟，主要是因为它们在静态培养下分化为心肌细胞，这种培养只复制生物分子信号，而忽略了在心脏发生过程中塑造心脏早期和晚期发育的动态血流动力学信号。为了评价血液动力学刺激对HiPSC-CM成熟的影响，我们使用仿生心脏组织模型(BCTM)，再现了与心脏发育相关的血流动力学和压力-容量变化。在7天的逐渐增加的刺激后，我们发现血流动力学负荷导致(A)细胞与细胞外基质(ECM)的排列增强，(B)与生理性肥大相关的基因显著增加，(C)肌节组织的显著变化和细胞代谢的潜在变化，以及(D)提示正向力频率响应(FFR)的缩短率显著增加。这些发现表明，在准确复制血流动力学信号的条件下培养HiPSC-CMS，可以产生与器官生长和功能成熟一致的结构组织和分子信号。
Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) hold great promise for cardiovascular disease modeling and regenerative medicine. However, hiPSC-CMs are both structurally and functionally immature primarily due to their differentiation into cardiomyocytes occurring under static culture which only reproduces biomolecular cues and ignores the dynamic hemodynamic cues that shape early and late heart development during cardiogenesis. In order to evaluate the effects of hemodynamic stimuli on hiPSC-CM maturation we used the Biomimetic Cardiac Tissue Model (BCTM), to reproduce the hemodynamics and pressure-volume changes associated with heart development. Following 7 days of gradually increasing stimulation we show that hemodynamic loading results in (a) enhanced alignment of the cells and extracellular matrix (ECM), (b) significant increases in genes associated with physiological hypertrophy, (c) noticeable changes in sarcomeric organization and potential changes to cellular metabolism and (d) a significant increase in fractional shortening suggestive of a positive force frequency response (FFR). These findings suggest that culture of hiPSC-CMs under conditions that accurately reproduce hemodynamic cues results in structural organization and molecular signaling consistent with organ growth and functional maturation.
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影响因子：
16.1
作者：
Feric NT;Radisic M
通讯作者：
Radisic M
影响因子：
17.1
作者：
Matsa E;Burridge PW;Wu JC
通讯作者：
Wu JC
影响因子：
2.8
作者：
CLARK, EB;HU, N;ROSENQUIST, GC
通讯作者：
ROSENQUIST, GC
DOI：
10.1196/annals.1380.017
发表时间：
2006-01-01
期刊：
INTERACTIVE AND INTEGRATIVE CARDIOLOGY
影响因子：
--
作者：
Itzhaki, Ilanit;Schiller, Jackie;Gepstein, Lior
通讯作者：
Gepstein, Lior
影响因子：
3.4
作者：
Nakamura, Kenta;Hirano, Ken-ichi;Wu, Sean M.
通讯作者：
Wu, Sean M.