Enhancing the engraftment of human induced pluripotent stem cell-derived cardiomyocytes via a transient inhibition of rho kinase activity

Meng Zhao, Yawen Tang, Patrick J. Ernst, Asher Kahn-Krell, Chengming Fan, Danielle Pretorius, Hanxi Zhu, Xi Lou, Lufang Zhou, Jianyi Zhang, Wuqiang Zhu

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

A crucial factor in improving cellular therapy effectiveness for myocardial regeneration is to safely and efficiently increase the cell engraftment rate. Y-27632 is a highly potent inhibitor of Rho-associated, coiled-coil-containing protein kinase (RhoA/ROCK) and is used to prevent dissociation-induced cell apoptosis (anoikis). We demonstrate that Y-27632 pretreatment for human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs+RI) prior to implantation results in a cell engraftment rate improvement in a mouse model of acute myocardial infarction (MI). Here, we describe a complete procedure of hiPSC-CMs differentiation, purification, and cell pretreatment with Y-27632, as well as the resulting cell contraction, calcium transient measurements, and transplantation into mouse MI models. The proposed method provides a simple, safe, effective, and low-cost method which significantly increases the cell engraftment rate. This method cannot only be used in conjunction with other methods to further enhance the cell transplantation efficiency but also provides a favorable basis for the study of the mechanisms of other cardiac diseases.

Original languageEnglish (US)
Article numbere59452
JournalJournal of Visualized Experiments
Volume2019
Issue number149
DOIs
StatePublished - Jul 2019

Keywords

  • Biochemistry
  • Cardiomyocytes
  • Cell therapy
  • Issue 149
  • Myocardial infarction
  • Pluripotent stem cells
  • ROCK inhibitor
  • Rho kinase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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