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Human Biopsies in Nanofibrillar Cellulose Hydrogel – A Novel Method for Long-term Tissue Culture

Johanna Niklander, Raili Koivuniemi, Alexander Stallinger, Florian Kleinegger, Lauri Paasonen, Silke Schrom, Bernadette Liegl-Atzwanger, Iris Zalaudek, Gord von Campe, Georg Singer, Johannes Haybaeck, Marjo Yliperttula, Beate Rinner
doi: https://doi.org/10.1101/2021.11.22.466872
Johanna Niklander
1Drug Research Program, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland
2Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria
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Raili Koivuniemi
1Drug Research Program, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland
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Alexander Stallinger
2Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria
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Florian Kleinegger
2Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria
3Diagnostic and Research Center for Molecular Biomedicine, Institute of Pathology, Medical University of Graz, 8010 Graz, Austria
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Lauri Paasonen
4UPM-Kymmene Corporation, UPM Biomedicals, 00101 Helsinki, Finland
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Silke Schrom
2Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria
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Bernadette Liegl-Atzwanger
3Diagnostic and Research Center for Molecular Biomedicine, Institute of Pathology, Medical University of Graz, 8010 Graz, Austria
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Iris Zalaudek
5Department of Dermatology and Venerology, University of Trieste, 35124 Trieste, Italy
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Gord von Campe
6Department of Neurosurgery, Medical University of Graz, 8036 Graz, Austria
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Georg Singer
7Department of Pediatric and Adolescent Surgery, Medical University of Graz, 8036 Graz, Austria
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Johannes Haybaeck
3Diagnostic and Research Center for Molecular Biomedicine, Institute of Pathology, Medical University of Graz, 8010 Graz, Austria
8Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, 6020 Innsbruck, Austria
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Marjo Yliperttula
1Drug Research Program, Faculty of Pharmacy, University of Helsinki, 00014 Helsinki, Finland
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Beate Rinner
2Division of Biomedical Research, Medical University of Graz, 8036 Graz, Austria
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  • For correspondence: beate.rinner@medunigraz.at
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Abstract

Advanced 3D in vitro models are laborious to prepare and susceptible to unintentional design errors due to culture adaptations, cell immaturity, xenofactors or yet incomplete knowledge of the dynamics within tissues or materials. In order to acquire cost-efficient research material with intact in vivo composition, we developed novel tissue culture method with plant-derived scaffolding.

Human skin-, foreskin- and glioblastoma multiforme biopsies were dissected mechanically and cultivated for 28 days in plant-derived nanofibrillar cellulose hydrogel. Comparative cultures were done using mouse sarcoma tumor –derived Matrigel™. Long-term preservation of cultivated tissues was evaluated against typical immunohistochemical biomarkers for each tissue type: skin tissues for cytokeratins 5/6, E-cadherin and vimentin for sustained tissue structures, and brain neoplasia for Olig2, S100, Nestin, NOTCH1, MAP2 and GFAP for preserved disease profile.

Histological analysis from both culture conditions showed that until day 28, all cultivated biopsy types were able to sustain their characteristic protein expressions without signs of necrosis. We here conclude a novel tissue culture model in xeno-free 3D scaffolding, that can enable long-term sample storage in vitro, studies of human tumor tissues and their non-neoplastic microenvironment, and innovations in personalized medicine research.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 22, 2021.
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Human Biopsies in Nanofibrillar Cellulose Hydrogel – A Novel Method for Long-term Tissue Culture
Johanna Niklander, Raili Koivuniemi, Alexander Stallinger, Florian Kleinegger, Lauri Paasonen, Silke Schrom, Bernadette Liegl-Atzwanger, Iris Zalaudek, Gord von Campe, Georg Singer, Johannes Haybaeck, Marjo Yliperttula, Beate Rinner
bioRxiv 2021.11.22.466872; doi: https://doi.org/10.1101/2021.11.22.466872
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Human Biopsies in Nanofibrillar Cellulose Hydrogel – A Novel Method for Long-term Tissue Culture
Johanna Niklander, Raili Koivuniemi, Alexander Stallinger, Florian Kleinegger, Lauri Paasonen, Silke Schrom, Bernadette Liegl-Atzwanger, Iris Zalaudek, Gord von Campe, Georg Singer, Johannes Haybaeck, Marjo Yliperttula, Beate Rinner
bioRxiv 2021.11.22.466872; doi: https://doi.org/10.1101/2021.11.22.466872

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