期刊
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fbioe.2022.908848
关键词
pluripotent stem cell; cardiomyocyte; suspension culture; maturation; organoids; biomanufacturing
资金
- National Heart, Lung, and Blood Institute
- American Heart Association Pre-doctoral Award [5R01HL114120, 5R01HL131017, 5U01HL134764]
- National Institute of General Medical Sciences [19PRE34380402]
- National Institute of Biomedical Imaging and Bioengineering [T32GM008361]
- [T32EB023872]
Researchers introduce a simple and reproducible 3D culture method for generating cardiac spheroids, which contain cardiomyocytes, vascular cells and cardiac fibroblasts. This method promotes cardiomyocyte maturation and improves their bioenergetics.
Cardiomyocytes (CMs), endothelial cells (ECs), smooth-muscle cells (SMCs), and cardiac fibroblasts (CFs) differentiated from human induced-pluripotent stem cells (hiPSCs) are the fundamental components of cell-based regenerative myocardial therapy and can be used as in-vitro models for mechanistic studies and drug testing. However, newly differentiated hiPSC-CMs tend to more closely resemble fetal CMs than the mature CMs of adult hearts, and current techniques for improving CM maturation can be both complex and labor-intensive. Thus, the production of CMs for commercial and industrial applications will require more elementary methods for promoting CM maturity. CMs tend to develop a more mature phenotype when cultured as spheroids in a three-dimensional (3D) environment, rather than as two-dimensional monolayers, and the activity of ECs, SMCs, and CFs promote both CM maturation and electrical activity. Here, we introduce a simple and reproducible 3D-culture-based process for generating spheroids containing all four cardiac-cell types (i.e., cardiac spheroids) that is compatible with a wide range of applications and research equipment. Subsequent experiments demonstrated that the inclusion of vascular cells and CFs was associated with an increase in spheroid size, a decline in apoptosis, an improvement in sarcomere maturation and a change in CM bioenergetics.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据