Three-dimensional cell culture of human mesenchymal stem cells in nanofibrillar cellulose hydrogels
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iomaterials for 3D Cell Biology Research Letter
Three-dimensional cell culture of human mesenchymal stem cells in nanofibrillar cellulose hydrogels Ioannis Azoidis and Joel Metcalfe, Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights Campus, Reading RG6 6AP, UK James Reynolds, Lein Applied Diagnostics Ltd, Reading Enterprise Centre, Whiteknights Road, Reading RG6 6BU, UK Shirley Keeton, Cell Migration Lab, School of Biological Sciences, University of Reading, Whiteknights Campus, Reading RG6 6AP, UK Sema S. Hakki, Selcuk University Faculty of Dentistry Department of Periodontology Campus, 42079 Konya, Turkey Jonathan Sheard, Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights Campus, Reading RG6 6AP, UK; Sheard BioTech Limited, Suite LP36133, 20-22, Wenlock Road, London N17GU, UK Darius Widera, Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights Campus, Reading RG6 6AP, UK Address all correspondence to Darius Widera at [email protected] (Received 31 May 2017; accepted 18 July 2017)
Abstract Human mesenchymal stem cells (MSCs) are the most intensely studied and clinically used adult stem cell type. Conventional long-term cultivation of MSCs as a monolayer is known to result in a reduction of their functionality and viability. In addition, large volumes of cell culture medium are required to obtain cell quantities needed for their clinical use. In this proof of concept study, we cultivated human MSCs within a three-dimensional nanofibrillar cellulose (NFC) hydrogel. We show that NFC is biocompatible with human MSCs, and represents a feasible approach to upscaling of their culture.
Introduction The presence of human mesenchymal stem cells (MSCs) in multiple tissue types as well as their multi-lineage differentiation and regenerative capacity has led to an increase in their clinical application with over 724 trials registered on ClinicalTrials.gov as of May 2017. The therapeutic benefit of MSC-administration in different pathologies (reviewed in [1]) can be at least partly explained by paracrine effects on endogenous regeneration that are mainly mediated by extracellular vesicles (EVs) released by MSCs.[2–4] Thus, EVs are considered to represent a cost-efficient alternative to transplantation of MSCs with a potentially equally beneficial therapeutic outcome. Notably, both transplantation of MSCs and manufacturing of MSC-derived EVs require large cell numbers, long cultivation time, and consequently large volumes of cell culture medium. Thus, culture expansion in vitro is a necessary step in order to obtain sufficient quantities of cells for the intended therapeutic application. However, it is well known that during initial and extended in vitro culture expansion, MSCs accumulate chromosomal aberrations, which may be caused by the extraction of the cells from their three-dimensional (3D) endogenous niche and two-dimensional (2D) in vitro culture conditions.
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