Centrifugal Heart‑on‑Chip: A versatile platform for cardiac μ‑tissue generation and analysis

Heart-on-chip system with eight parallel cultivation chambers.
Centrifugal heart-on-chip system with eight parallel culture chambers.
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User-friendly tissue generation via centrifugation.

Despite considerable research efforts, cardiovascular diseases still constitute a major cause of death. Novel biological breakthroughs such as the emergence of human induced pluripotent stem cells (iPSCs) and the generation of engineered cardiac tissue models offer immense potential for pharmaceutical R&D as well as precision medicine. Current model systems, however, require large amounts of cells and rely on complex cell injection protocols, hampering the adoption of the technologies and fulfillment of their promises.

We have developed a centrifugal Heart‑on‑Chip (HoC) platform with the potential to be a widely‑applicable, user‑friendly tool. The platform allows for a parallelized generation of cardiac µ‑tissues, mimicking a minimal functional unit of the heart muscle. It is based on simple centrifugation steps utilizing basic infrastructure present in all cell culture laboratories. The HoC provides a physiologically relevant in vitro model which can be utilized for drug testing or disease modelling. In the next project stage, we will integrate read‑out capabilities for the in situ determination of contractile forces and electrophysiological parameters as well as introduce external stimuli to improve tissue maturation.

All in all, the novel centrifugal HoC represents a fit-for‑purpose system which can be used by any laboratory and tailored for each specific application. This downscaled physiological model system offers unprecedented opportunities in cardiovascular research harnessing the true potential of iPSC technology.

Publications

  • O. Schneider, L. Zeifang, S. Fuchs, C. Sailer, P. Loskill*
    “User-friendly and paralleled generation of hiPSC-derived μ-tissues in a centrifugal heart-on-a-chip“
    Tissue Eng. 25, 786-798 (2019); https://doi.org/10.1089/ten.TEA.2019.0002
  • N. Huebsch, P. Loskill, N. Deveshwar, C. I. Spencer, L. Judge, M. A. Mandegar, C. Fox, T. Mohammed, Z. Ma, A. Mathur, A. S. Sheehan, A. Truong, M. Saxton, J. Yoo, D. Srivastava, T. A. Desai, P.-L. So, K. E. Healy, B. R. Conklin
    “Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses“
    Sci. Rep. 6, 24726 (2016); http://www.dx.doi.org/10.1038/srep24726
  • A. Mathur, Z. Ma, P. Loskill, S. Jeeawoody, K. E. Healy
    “In Vitro Cardiac Tissue Models: Current Status and Future Prospects“
    Adv. Drug. Deliv. Rev. 96, 203-213 (2016); http://www.dx.doi.org/10.1016/j.addr.2015.09.011
  • A. Mathur, P. Loskill, K. Shao, N. Huebsch, S. Hong, S. G. Marcus, N. Marks, L. P. Lee, B. Conklin, K. E. Healy
    “Human iPSC-based Cardiac Microphysiological System For Drug Screening Applications“
    Sci. Rep. 5, 8883 (2015); http://dx.doi.org/10.1038/srep08883
  • N. Huebsch#, P. Loskill#, M. A. Mandegar, N. Marks, A. S. Sheehan, Z. Ma, A. Mathur, T. N. Nguyen, J. Yoo, L. Judge, C. Spencer, A. Chukka, C. Russell, P.L. So, B. Conklin, K.E. Healy
    “Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem-Derived Cardiomyocytes Cultured over Different Spatial Scales“
    Tissue Eng. 21, 1-13 (2015); http://dx.doi.org/10.10
    89/ten.TEC.2014.0283