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dc.contributor.authorJiang, Bin
dc.contributor.authorOu, Wenquan
dc.contributor.authorShamul, James G.
dc.contributor.authorChen, Hao
dc.contributor.authorVan Belleghem, Sarah
dc.contributor.authorStewart, Samantha
dc.contributor.authorLiu, Zhenguo
dc.contributor.authorFisher, John P.
dc.contributor.authorHe, Xiaoming
dc.date.accessioned2021-08-12T13:03:49Z
dc.date.available2021-08-12T13:03:49Z
dc.date.issued2021-08-02
dc.identifier.urihttp://hdl.handle.net/10713/16375
dc.description.abstractCardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) are valuable for the understanding/treatment of the deadly heart diseases and their drug screening. However, the very much needed homogeneous 3D cardiac differentiation of human iPSCs is still challenging. Here, it is discovered surprisingly that Rock inhibitor (RI), used ubiquitously to improve the survival/yield of human iPSCs, induces early gastrulation-like change to human iPSCs in 3D culture and may cause their heterogeneous differentiation into all the three germ layers (i.e., ectoderm, mesoderm, and endoderm) at the commonly used concentration (10 μM). This greatly compromises the capacity of human iPSCs for homogeneous 3D cardiac differentiation. By reducing the RI to 1 μM for 3D culture, the human iPSCs retain high pluripotency/quality in inner cell mass-like solid 3D spheroids. Consequently, the beating efficiency of 3D cardiac differentiation can be improved to more than 95 % in ~7 days (compared to less than ~50 % in 14 days for the 10 μM RI condition). Furthermore, the outset beating time (OBT) of all resultant cardiac spheroids (CSs) is synchronized within only 1 day and they form a synchronously beating 3D construct after 5-day culture in gelatin methacrylol (GelMA) hydrogel, showing high homogeneity (in terms of the OBT) in functional maturity of the CSs. Moreover, the resultant cardiomyocytes are of high quality with key functional ultrastructures and highly responsive to cardiac drugs. These discoveries may greatly facilitate the utilization of human iPSCs for understanding and treating heart diseases. © 2021 The Authorsen_US
dc.description.sponsorshipNational Science Foundationen_US
dc.description.urihttps://doi.org/10.1016/j.bioactmat.2021.07.013en_US
dc.language.isoenen_US
dc.publisherKeAi Communications Co.en_US
dc.relation.ispartofBioactive Materialsen_US
dc.subjectCardiomyocyteen_US
dc.subjectEpisomalen_US
dc.subjectGelMAen_US
dc.subjectiPSCen_US
dc.subjectSpheroiden_US
dc.titleRock inhibitor may compromise human induced pluripotent stem cells for cardiac differentiation in 3Den_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.bioactmat.2021.07.013


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