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Finola Cliffe, Patrick Costello, Conor Madden, Shane Devitt, Sumir Ramesh Mukkunda, Bhairavi Bengaluru Keshava, Howard Fearnhead, Aiste Vitkuaskaite, Mashid Dehkordi, Walter Chingwaru, Milosz Przyjalgowski, Natalia Rebrova, Mark Lyons
https://www.biorxiv.org/content/10.1101/2022.08.30.505827v1.abstract
There is an urgent need for scalable Microphysiological Systems (MPS’s)1 that can better predict drug efficacy and toxicity at the preclinical screening stage. Here we present Mera, an automated, modular and scalable system for culturing and assaying microtissues with inbuilt environment control and automated image capture. The paradigm presented involves culturing and maturing common microtissue types in rows (rows of e.g., liver, heart, gastro-intestinal or kidney microtissues) and then reorienting fluid flow to create a recirculating circuit composed of inter-connected columns containing distinct microtissues (e.g. individual fluidic circuits with liver, heart, gastrointestinal and kidney micro-tissues inter-connected) to allow drugging or staining. We present data demonstrating the prototype system using an Acetaminophen/HepG2 liver microtissue toxicity assay with Calcein AM and Ethidium Homodimer viability assays. We demonstrate the functionality of the automated image capture system. The prototype microtissue culture plate wells are laid out in a 3×3 or 4×10 grid with viability and toxicity assays demonstrated in both formats. In this paper we set the groundwork for the Mera system as a viable option for scalable microtissue culture and assay development.
Vidmar J, Chingwaru C, Chingwaru W.
Abstract
http://1-s2.0-S0022480416304565-main
Rapid and efficient healing of damaged tissue is critical for the restoration of tissue function and avoidance of tissue defects. Many in vitro cell models have been described for wound healing studies; however, the mechanisms that underlie the process, especially in chronic or complicated wounds, are not fully understood. The identification of cell culture systems that closely simulate the physiology of damaged tissue in vivo is necessary. We describe the cell culture models that have enhanced our understanding, this far, of the wound healing process or have been used in drug discovery. Cell cultures derived from the epithelium, including corneal, renal, intestinal (IEC-8 cells and IEC-6), skin epithelial cells (keratinocytes, fibroblasts, and multipotent mesenchymal stem cells), and the endothelium (human umbilical vein endothelial cells, primary mouse endothelial cells, endodermal stem cells, human mesenchymal stem cells, and corneal endothelial cells) have played a pivotal role toward our understanding of the mechanisms of wound healing. More studies are necessary to develop co-culture cell models which closely simulate the environment of a wound in vivo. Cell culture models are invaluable tools to promote our understanding of the mechanisms that regulate the wound healing process and provide a platform for drug discovery.
L Nissen, W Chingwaru, B Sgorbati, B Biavati, A Cencic
Rapid and efficient healing of damaged tissue is critical for the restoration of tissue function and avoidance of tissue defects. Many in vitro cell models have been described for wound healing studies; however, the mechanisms that underlie the process, especially in chronic or complicated wounds, are not fully understood. The identification of cell culture systems that closely simulate the physiology of damaged tissue in vivo is necessary. We describe the cell culture models that have enhanced our understanding, this far, of the wound healing process or have been used in drug discovery. Cell cultures derived from the epithelium, including corneal, renal, intestinal (IEC-8 cells and IEC-6), skin epithelial cells (keratinocytes, fibroblasts, and multipotent mesenchymal stem cells), and the endothelium (human umbilical vein endothelial cells, primary mouse endothelial cells, endodermal stem cells, human mesenchymal stem cells, and corneal endothelial cells) have played a pivotal role toward our understanding of the mechanisms of wound healing. More studies are necessary to develop co-culture cell models which closely simulate the environment of a wound in vivo. Cell culture models are invaluable tools to promote our understanding of the mechanisms that regulate the wound healing process and provide a platform for drug discovery.
