Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.03.23.533840v1?rss=1

Authors: Perocheau, D. P., Baruteau, J., Gurung, S., Touramanidou, L., Duff, C., Sharma, G., Sebire, N., Finn, P., Cavedon, A., Siddiqui, S., Rice, L., Martini, P., Frassetto, A.

Abstract:
In academic research and the pharmaceutical industry, in vitro single cell line cultures and in vivo animal models are considered as gold standards in modelling diseases and assessing therapeutic efficacy. However, both models have limitations, with incomplete reproduction of pathophysiological characteristics and absence of 3-dimensional architecture with cell lines or the use of live animals brings ethical considerations, limiting the experimental scale and design. The use of precision-cut tissue slices can bridge the gap between these mainstream models as this technique combines the advantages of studying all cell sub-types whilst preserving the tissue-matrix architecture, thereby closely mimicking a mini-organ. Here, we describe an optimised and easy-to-implement protocol for the culture of sections from mouse livers. We show that precision-cut liver sections can be a reliable model for recapitulating the biological phenotype of inherited metabolic diseases, exemplified by common urea cycle defects citrullinemia type 1 and argininosuccinic aciduria, caused by argininosuccinic synthase (ASS1) and argininosuccinic lyase (ASL) deficiencies respectively. Therapeutic response to gene therapy such as messenger RNA replacement delivered via lipid nanoparticles can be monitored, demonstrating that precision-cut liver sections can be used as a preclinical screening tool to assess therapeutic response and toxicity in monogenic liver diseases.

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