Conversion of Unmodified Stem Cells to Pacemaker Cells by Overexpression of Key Developmental Genes

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2023 Jul 6

PMID 37408215

Authors

Tahereh Karimi

Zhizhong Pan

Vladimir N Potaman

Eckhard U Alt

Affiliations

Soon will be listed here.

Abstract

Arrhythmias of the heart are currently treated by implanting electronic pacemakers and defibrillators. Unmodified adipose tissue-derived stem cells (ASCs) have the potential to differentiate into all three germ layers but have not yet been tested for the generation of pacemaker and Purkinje cells. We investigated if-based on overexpression of dominant conduction cell-specific genes in ASCs-biological pacemaker cells could be induced. Here we show that by overexpression of certain genes that are active during the natural development of the conduction system, the differentiation of ASCs to pacemaker and Purkinje-like cells is feasible. Our study revealed that the most effective procedure consisted of short-term upregulation of gene combinations SHOX2-TBX5-HCN2, and to a lesser extent SHOX2-TBX3-HCN2. Single-gene expression protocols were ineffective. Future clinical implantation of such pacemaker and Purkinje cells, derived from unmodified ASCs of the same patient, could open up new horizons for the treatment of arrythmias.

Citing Articles

Pacemaker Channels and the Chronotropic Response in Health and Disease.

Hennis K, Piantoni C, Biel M, Fenske S, Wahl-Schott C Circ Res. 2024; 134(10):1348-1378.

PMID: 38723033 PMC: 11081487. DOI: 10.1161/CIRCRESAHA.123.323250.

Application of adipose-derived stem cells in ischemic heart disease: theory, potency, and advantage.

Xiao W, Shi J Front Cardiovasc Med. 2024; 11:1324447.

PMID: 38312236 PMC: 10834651. DOI: 10.3389/fcvm.2024.1324447.

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