4.6 Article

Rat atrial engineered heart tissue: a new in vitro model to study atrial biology

期刊

BASIC RESEARCH IN CARDIOLOGY
卷 113, 期 5, 页码 -

出版社

SPRINGER HEIDELBERG
DOI: 10.1007/s00395-018-0701-2

关键词

Atrial fibrillation; Tissue engineering; Electrophysiology; Drug screening

资金

  1. DZHK (German Centre for Cardiovascular Research)
  2. German Ministry of Education and Research (BMBF)
  3. e:Med symAtrial consortium
  4. BMBF initiative

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Engineered heart tissue (EHT) from rat cells is a useful tool to study ventricular biology and cardiac drug safety. Since atrial and ventricular cells differ significantly, EHT and other 3D cell culture formats generated from ventricular cells have been of limited value to study atrial biology. To date, reliable in vitro models that reflect atrial physiology are lacking. Therefore, we established a novel EHT model using rat atrial cells (atrial EHT, aEHT) to assess atrial physiology, contractility and drug response. The tissue constructs were characterized with regard to gene expression, histology, electrophysiology, and the response to atrial-specific drugs. We observed typical functional properties of atrial tissue in our model such as more regular spontaneous beating with lower force, shorter action potential duration, and faster contraction and relaxation compared to ventricular EHT (vEHT). The expression of atrial-specific genes and proteins was high, whereas ventricle-specific transcripts were virtually absent. The atrial-selective drug carbachol had a strong negative inotropic and chronotropic effect on aEHT only. Taken together, the results demonstrate the feasibility of aEHT as a novel atrial 3D model and as a benchmark for tissue engineering with human induced pluripotent stem cell-derived atrial-like cardiomyocytes. Atrial EHT faithfully recapitulates atrial physiology and shall be useful to study atrial molecular physiology in health and disease as well as drug response.

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