Direct hydrogel encapsulation of pluripotent stem cells enables ontomimetic differentiation and growth of engineered human heart tissues

Biomaterials
Petra KerscherElizabeth A Lipke

Abstract

Human engineered heart tissues have potential to revolutionize cardiac development research, drug-testing, and treatment of heart disease; however, implementation is limited by the need to use pre-differentiated cardiomyocytes (CMs). Here we show that by providing a 3D poly(ethylene glycol)-fibrinogen hydrogel microenvironment, we can directly differentiate human pluripotent stem cells (hPSCs) into contracting heart tissues. Our straight-forward, ontomimetic approach, imitating the process of development, requires only a single cell-handling step, provides reproducible results for a range of tested geometries and size scales, and overcomes inherent limitations in cell maintenance and maturation, while achieving high yields of CMs with developmentally appropriate temporal changes in gene expression. We demonstrate that hPSCs encapsulated within this biomimetic 3D hydrogel microenvironment develop into functional cardiac tissues composed of self-aligned CMs with evidence of ultrastructural maturation, mimicking heart development, and enabling investigation of disease mechanisms and screening of compounds on developing human heart tissue.

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Citations

Jun 9, 2016·Cellular and Molecular Life Sciences : CMLS·I Y ShadrinN Bursac
Sep 13, 2016·Journal of Biomedical Materials Research. Part a·Shantanu PradhanElizabeth A Lipke
Apr 30, 2017·Circulation Research·Florian WeinbergerThomas Eschenhagen
Feb 18, 2018·Scientific Reports·Shantanu PradhanElizabeth A Lipke
Apr 11, 2019·Tissue Engineering. Part a·Tracy A HookwayTodd C McDevitt
Jun 6, 2020·Annual Review of Biomedical Engineering·Erica A CastilloBeth L Pruitt
Sep 18, 2020·Experimental Biology and Medicine·Keri Dame, Alexandre Js Ribeiro
Sep 15, 2020·Advanced Biosystems·Matthew R ArkenbergChien-Chi Lin
Feb 8, 2019·Tissue Engineering. Part a·Alicia C B AllenJanet Zoldan
May 30, 2019·Bioengineering·Minh Nguyen Tuyet Le, Kouichi Hasegawa
Jan 10, 2019·Frontiers in Physiology·Abdul Jalil RufaihahDror Seliktar
Nov 25, 2020·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·Rui ZhangFeng Lan
Nov 17, 2020·Frontiers in Cardiovascular Medicine·Dillon K JarrellJeffrey G Jacot
Jun 3, 2021·Npj Regenerative Medicine·Miguel F TenreiroMargarida Serra
Aug 26, 2017·Biomacromolecules·Indra ApsiteLeonid Ionov
Aug 14, 2017·ACS Biomaterials Science & Engineering·Petra KerscherElizabeth A Lipke
Nov 12, 2018·ACS Biomaterials Science & Engineering·Carley OrtKibret Mequanint

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