0406 : Keratinocyte-derived cardiomyocytes provide in vivo biological pacemaker function

Autor: Yevgeniy Anyukhovskiy, Shelly Naor, Peter R. Brink, Xiaolangshaw Qiu, Ya-Ping Jiang, Meital Ben-Ari, Irina A. Potapova, Michael R. Rosen, Ira L. Cohen, Stephanie Burke, Tania Rahim, Samuel Chauveau, Peter Danilo, Binah Binah
Rok vydání: 2016
Předmět:
Zdroj: Archives of Cardiovascular Diseases Supplements. 8:257
ISSN: 1878-6480
DOI: 10.1016/s1878-6480(16)30505-5
Popis: Objective We investigated pacemaker function of iPSC-CM in a canine complete heart block model. Methods Embryoid bodies (EBs) were derived from human keratinocytes and their gene expression profile and markers of differentiation were identified. We recorded their action potential characteristics, including phase 4 depolarization, automaticity, response to ivabradine, and pacemaker current, If, as well. Atrio-ventricular blocked dogs were immunosuppressed and instrumented with a VVI pacemaker. Forty-75 rhythmically contracting EBs (totaling 1.3-2x106 cells) were injected subepicardially into the anterobasal left ventricle. ECGs and 24-h Holter recordings were made biweekly. After 4- 13 weeks, epinephrine (EPI) (1 μg/Kg/min) was infused and the heart removed for histological or electrophysiological study. Results IPSC-CMs largely lost their markers of pluripotency and were positive for cardiac-specific markers instead. Automaticity of IPSC-CMs was identified and confirmed to be If-dependent. Epicardial pacing of the injection site identified matching beats arising from that site by the end of week 1 of implantation. By week 4, 20% of beats were electronically paced and 60-80% of beats were matching. Maximum night and day rates of matching beats were 53±6.9 and 68±10.4 bpm respectively at 4 weeks. EPI increased rate of matching beats from 35±4.3 to 65±4.0 bpm. Incubation of EBs with the vital dye, Dil, revealed the persistence of injected cells at the site of administration. Conclusions IPSC-CM can integrate into host myocardium and create a biological pacemaker. While this is a promising development, rate and rhythm of the iPSC-CM pacemakers remain to be optimized. The author hereby declares no conflict of interest
Databáze: OpenAIRE
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