Micropattern platform promotes extracellular matrix remodeling by human PSC-derived cardiac fibroblasts and enhances contractility of co-cultured cardiomyocytes.
Micropattern platform promotes extracellular matrix remodeling by human PSC-derived cardiac fibroblasts and enhances contractility of co-cultured cardiomyocytes.
复制标题
DOI：
10.14814/phy2.15045
复制
发表时间：
2021-10
影响因子：
2.5
通讯作者：
Crone WC
中科院分区：
文献类型：
--
作者：
Napiwocki BN;Stempien A;Lang D;Kruepke RA;Kim G;Zhang J;Eckhardt LL;Glukhov AV;Kamp TJ;Crone WC
In native heart tissue, cardiac fibroblasts provide the structural framework of extracellular matrix (ECM) while also influencing the electrical and mechanical properties of cardiomyocytes. Recent advances in the field of stem cell differentiation have led to the availability of human pluripotent stem cell‐derived cardiac fibroblasts (iPSC‐CFs) in addition to cardiomyocytes (iPSC‐CMs). Here we use a novel 2D in vitro micropatterned platform that provides control over ECM geometry and substrate stiffness. When cultured alone on soft micropatterned substrates, iPSC‐CFs are confined to the micropatterned features and remodel the ECM into anisotropic fibers. Similar remodeling and ECM production occurs when cultured with iPSC‐CMs in a co‐culture model. In addition to modifications in the ECM, our results show that iPSC‐CFs influence iPSC‐CM function with accelerated Ca2+ transient rise‐up time and greater contractile strains in the co‐culture conditions compared to when iPSC‐CMs are cultured alone. These combined observations highlight the important role cardiac fibroblasts play in vivo and the need for co‐culture models like the one presented here to provide more representative in vitro cardiac constructs. For the first time, human PSC‐derived cardiomyocytes and cardiac fibroblasts are co‐cultured on a micropatterned platform which results in enhanced contractility and accelerated Ca2+ transient rise‐up time of the cardiomyocytes. The micropattern platform controls the alignment of cardiomyocytes as well as the migration and extracellular matrix remodeling by cardiac fibroblasts. Biomimetic platforms with multiple cell sources will enhance understanding of cardiovascular physiology and allow for more relevant in vitro cardiac constructs.
登录
查看更多内容
基因纯化的人诱导多能干细胞衍生的心肌细胞单层的同步电压和钙图谱。
影响因子：
20.1
作者：
Lee P;Klos M;Bollensdorff C;Hou L;Ewart P;Kamp TJ;Zhang J;Bizy A;Guerrero-Serna G;Kohl P;Jalife J;Herron TJ
通讯作者：
Herron TJ
影响因子：
4.6
作者：
Liau B;Jackman CP;Li Y;Bursac N
通讯作者：
Bursac N
影响因子：
12.6
作者：
Dou, Wenkun;Zhao, Qili;Sun, Yu
通讯作者：
Sun, Yu
影响因子：
15.9
作者：
MacKenna, DA;Dolfi, F;Ruoslahti, E
通讯作者：
Ruoslahti, E
影响因子：
1.2
作者：
Bizy, Alexandra;Guerrero-Serna, Guadalupe;Hu, Bin;Ponce-Balbuena, Daniela;Willis, B. Cicero;Zarzoso, Manuel;Ramirez, Rafael J.;Sener, Michelle F.;Mundada, Lakshmi V.;Klos, Matthew;Devaney, Eric J.;Vikstrom, Karen L.;Herron, Todd J.;Jalife, Jose
通讯作者：
Jalife, Jose