Functional Toxicology and Pharmacology Test of Cell Induced Mechanical Tensile Stress in 2D and 3D Tissue Cultures
Mechanical forces/tensile stresses are critical determinants of cellular growth, differentiation and migration patterns in health and disease. The innovative “CellDrum technology” was designed for measuring mechanical tensile stress of cultured cell monolayers/thin tissue constructs routinely. These are cultivated on very thin silicone membranes in the so-called CellDrum. The cell layers adhere firmly to the membrane and thus transmit the cell forces generated. A CellDrum consists of a cylinder which is sealed from below with a 4 μm thick, biocompatible, functionalized silicone membrane. The weight of cell culture medium bulbs the membrane out downwards. Membrane indentation is measured. When cells contract due to drug action, membrane, cells and medium are lifted upwards. The induced indentation changes allow for lateral drug induced mechanical tension quantification of the micro-tissues. With hiPS-induced (human) Cardiomyocytes (CM) the CellDrum opens new perspectives of individualized cardiac drug testing. Here, monolayers of self-beating hiPS-CMs were grown in CellDrums. Rhythmic contractions of the hiPS-cells induce membrane up-and-down deflections. The recorded cycles allow for single beat amplitude, single beat duration, integration of the single beat amplitude over the beat time and frequency analysis. Dose effects of agonists and antagonists acting on Ca2+ channels were sensitively and highly reproducibly observed. Data were consistent with published reference data as far as they were available. The combination of the CellDrum technology with hiPS-Cardiomyocytes offers a fast, facile and precise system for pharmacological and toxicological studies. It allows new preclinical basic as well as applied research in pharmacolgy and toxicology.
Some of our teachers remain a role model for our entire life. Gerhard Artmann’s role models remain the professors Y. C. Fung, Shu Chien (both UCSD, San Diego, USA), Georg Büldt (Research Center Juelich, Germany) and Peter Paufler, physicist and crystallographer (University of Dresden, Germany). For providing stem cell expertise and free disposal of hIPS derived, highly purified and well characterized hIPS derived cardiomyocytes as well as for his excellent scientific advice and kindness we owe special thanks to Professor Jürgen Hescheler.
All technological developments and scientific tasks related to the CellDrum technology were carried out in the laboratories and under the scientific direction of Professors Gerhard M. as well as Aysegül Artmann. Significant contributions to the work were made by Professor J. Trzewik our former Ph.D. student and major CellDrum co-inventor. Working with him was scientifically and technologically very productive. Thank you, Juergen. Professors Artmann thank their doctoral candidate M. Gossmann for his lab work. As his teachers, however, they are thoughtfully looking back at the time with him. Another but extremely talented doctoral candidate was P. Linder. He worked for more than a decade and a half intensively with us. We thank the young Prof. Dr. Ilya Digel for the excellent cooperation in the Institute of Bioengineering. In particular, we thank him for many stimulating scientific discussions and his ongoing loyalty.
Quite a number of CellDrum projects were financed by numerous grants to Professors Artmann received by the State of North Rhine Westphalia (NRW) as well as by funding institutions of the Government of the Federal Republic of Germany (BMBF, BMWI).
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