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Engineering biosynthetic excitable tissues from unexcitable cells for electrophysiological and cell therapy studies

Author

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  • Robert D. Kirkton

    (Duke University)

  • Nenad Bursac

    (Duke University)

Abstract

Patch-clamp recordings in single-cell expression systems have been traditionally used to study the function of ion channels. However, this experimental setting does not enable assessment of tissue-level function such as action potential (AP) conduction. Here we introduce a biosynthetic system that permits studies of both channel activity in single cells and electrical conduction in multicellular networks. We convert unexcitable somatic cells into an autonomous source of electrically excitable and conducting cells by stably expressing only three membrane channels. The specific roles that these expressed channels have on AP shape and conduction are revealed by different pharmacological and pacing protocols. Furthermore, we demonstrate that biosynthetic excitable cells and tissues can repair large conduction defects within primary 2- and 3-dimensional cardiac cell cultures. This approach enables novel studies of ion channel function in a reproducible tissue-level setting and may stimulate the development of new cell-based therapies for excitable tissue repair.

Suggested Citation

  • Robert D. Kirkton & Nenad Bursac, 2011. "Engineering biosynthetic excitable tissues from unexcitable cells for electrophysiological and cell therapy studies," Nature Communications, Nature, vol. 2(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1302
    DOI: 10.1038/ncomms1302
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    Cited by:

    1. Mao Mao & Xiaoli Qu & Yabo Zhang & Bingsong Gu & Chen Li & Rongzhi Liu & Xiao Li & Hui Zhu & Jiankang He & Dichen Li, 2023. "Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Tanmay A Gokhale & Jong M Kim & Robert D Kirkton & Nenad Bursac & Craig S Henriquez, 2017. "Modeling an Excitable Biosynthetic Tissue with Inherent Variability for Paired Computational-Experimental Studies," PLOS Computational Biology, Public Library of Science, vol. 13(1), pages 1-26, January.

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