Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart.
Engineering hiPSC-CM and hiPSC-EC laden 3D nanofibrous splenic hydrogel for improving cardiac function through revascularization and remuscularization in infarcted heart.
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DOI：
10.1016/j.bioactmat.2021.04.010
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发表时间：
2021-12
影响因子：
18.9
通讯作者：
Zhu C
中科院分区：
文献类型：
--
作者：
Guan G;Huo D;Li Y;Zhao X;Li Y;Qin Z;Sun D;Yang G;Yang M;Tan J;Zeng W;Zhu C
细胞治疗已成为心肌梗死（MI）后心脏修复的一种有前途的策略，但不良的缺血环境和低细胞递送效率仍然是重大挑战。脾脏作为造血干细胞龛，并在MI后分泌心脏保护因子，但目前尚不清楚它是否可用于人多能干细胞（hiPSC）培养，并为细胞移植物提供适当的微环境，以对抗缺血环境。在此，我们开发了脾细胞外基质衍生的温敏水凝胶（SpGel）。蛋白质组学分析表明，SpGel富含已知调节Wnt信号通路、细胞基质粘附、心肌收缩和氧化还原过程的蛋白质。体外研究表明，hiPSC可以有效地诱导为内皮细胞（iECs）和心肌细胞（iCMs），并在SpGel上增强功能。SpGel对iECs/iCMs抗氧化应激损伤的细胞保护作用也得到了证实。此外，体内研究表明，iEC/iCM负载SpGel通过改善细胞存活、血管再生和肌肉再生来改善心脏功能并抑制梗死心脏的心脏纤维化。总之，我们成功建立了一个高效生成和输送自体细胞移植物的新型平台，这可能是心肌梗死后心脏修复和再生的一种有前途的临床治疗策略。SpGel为hiPSC培养和分化提供了新的平台。SpGel为细胞移植提供了一个合适的微环境，以对抗体外氧化应激损伤。负载iEC/iCM的SpGel可改善细胞移植物保留，促进心脏功能恢复并抑制心脏纤维化。SpGel还可以用作未来3D打印心脏类器官的生物相容性生物墨水。
Cell therapy has been a promising strategy for cardiac repair after myocardial infarction (MI), but a poor ischemic environment and low cell delivery efficiency remain significant challenges. The spleen serves as a hematopoietic stem cell niche and secretes cardioprotective factors after MI, but it is unclear whether it could be used for human pluripotent stem cell (hiPSC) cultivation and provide a proper microenvironment for cell grafts against the ischemic environment. Herein, we developed a splenic extracellular matrix derived thermoresponsive hydrogel (SpGel). Proteomics analysis indicated that SpGel is enriched with proteins known to modulate the Wnt signaling pathway, cell-substrate adhesion, cardiac muscle contraction and oxidation-reduction processes. In vitro studies demonstrated that hiPSCs could be efficiently induced into endothelial cells (iECs) and cardiomyocytes (iCMs) with enhanced function on SpGel. The cytoprotective effect of SpGel on iECs/iCMs against oxidative stress damage was also proven. Furthermore, in vivo studies revealed that iEC/iCM-laden SpGel improved cardiac function and inhibited cardiac fibrosis of infarcted hearts by improving cell survival, revascularization and remuscularization. In conclusion, we successfully established a novel platform for the efficient generation and delivery of autologous cell grafts, which could be a promising clinical therapeutic strategy for cardiac repair and regeneration after MI. SpGel provides a novel platform for hiPSC culture and differentiation. SpGel provides a proper microenvironment for cell implants against oxidant stress damage in vitro. iEC/iCM-laden SpGel improves cell graft retention, promotes cardiac function recovery and inhibits cardiac fibrosis. SpGel could also be used as a biocompatible bioink for 3D printing cardiac organoids in the future.
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影响因子：
13.6
作者：
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影响因子：
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作者：
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1.2
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Couture LA