Engineering human ventricular heart tissue based on macroporous iron oxide scaffolds

Hui Yang; Lai Wei; Chen Liu; Weiyi Zhong; Bin Li; Yuncan Chen; Rui Han; Jiexian Zhuang; Jianxun Qu; Hongyue Tao; Haiyan Chen; Chen Xu; Qianqian Liang; Chao Lu; Ruizhe Qian; Sifeng Chen; Wenshuo Wang; Ning Sun

doi:10.1016/j.actbio.2019.02.024

Engineering human ventricular heart tissue based on macroporous iron oxide scaffolds

Acta Biomater. 2019 Apr 1:88:540-553. doi: 10.1016/j.actbio.2019.02.024. Epub 2019 Feb 16.

Authors

Hui Yang¹, Lai Wei², Chen Liu², Weiyi Zhong³, Bin Li³, Yuncan Chen³, Rui Han³, Jiexian Zhuang³, Jianxun Qu⁴, Hongyue Tao⁵, Haiyan Chen⁶, Chen Xu³, Qianqian Liang³, Chao Lu³, Ruizhe Qian³, Sifeng Chen³, Wenshuo Wang⁷, Ning Sun⁸

Affiliations

¹ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, Shanghai 200032, China; Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
² Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
³ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, Shanghai 200032, China.
⁴ GE Healthcare Applied Science Lab, United States.
⁵ Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China.
⁶ Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁷ Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: wang.wenshuo@zs-hospital.sh.cn.
⁸ Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Key Laboratory of Clinical Geriatric Medicine, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China. Electronic address: sunning@fudan.edu.cn.

PMID: 30779999
DOI: 10.1016/j.actbio.2019.02.024

Abstract

Myocardial infarction (MI) is a primary cardiovascular disease threatening human health and quality of life worldwide. The development of engineered heart tissues (EHTs) as a transplantable artificial myocardium provides a promising therapy for MI. Since most MIs occur at the ventricle, engineering ventricular-specific myocardium is therefore more desirable for future applications. Here, by combining a new macroporous 3D iron oxide scaffold (IOS) with a fixed ratio of human pluripotent stem cell (hPSC)-derived ventricular-specific cardiomyocytes and human umbilical cord-derived mesenchymal stem cells, we constructed a new type of engineered human ventricular-specific heart tissue (EhVHT). The EhVHT promoted expression of cardiac-specific genes, ion exchange, and exhibited a better Ca²⁺ handling behaviors and normal electrophysiological activity in vitro. Furthermore, when patched on the infarcted area, the EhVHT effectively promoted repair of heart tissues in vivo and facilitated the restoration of damaged heart function of rats with acute MI. Our results show that it is feasible to generate functional human ventricular heart tissue based on hPSC-derived ventricular myocytes for the treatment of ventricular-specific myocardium damage. STATEMENT OF SIGNIFICANCE: We successfully generated highly purified homogenous human ventricular myocytes and developed a method to generate human ventricular-specific heart tissue (EhVHT) based on three-dimensional iron oxide scaffolds. The EhVHT promoted expression of cardiac-specific genes, ion exchange, and exhibited a better Ca²⁺ handling behaviors and normal electrophysiological activity in vitro. Patching the EhVHT on the infarct area significantly improved cardiac function in rat acute MI models. This EhVHT has a great potential to meet the specific requirements for ventricular damages in most MI cases and for screening drugs specifically targeting ventricular myocardium.

Keywords: Engineered heart tissues; Iron oxide scaffolds; Myocardial infarction; Ventricular myocytes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / drug effects
Electrophysiological Phenomena
Ferric Compounds / pharmacology*
Heart Function Tests
Heart Ventricles / drug effects
Heart Ventricles / growth & development*
Heart Ventricles / transplantation
Heart Ventricles / ultrastructure
Male
Myocytes, Cardiac / drug effects
Myocytes, Cardiac / metabolism
Porosity
Rats, Sprague-Dawley
Tissue Engineering / methods*
Tissue Scaffolds / chemistry*

Substances

Ferric Compounds
ferric oxide