Multicentre comparison of biological and functional properties of mesenchymal stromal cells from different sources cultivated using a harmonised manufacturing workflow

Calcat-i-Cervera, Sandra, Rendra, Erika, Scaccia, Eleonora, Amadeo, Francesco, Hanson, Vivien, Wilm, Bettina, Murray, Patricia, O’Brien, Timothy, Taylor, Arthur and Bieback, Karen
(2022) Multicentre comparison of biological and functional properties of mesenchymal stromal cells from different sources cultivated using a harmonised manufacturing workflow. [Preprint]

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<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Mesenchymal stromal cells (MSCs), commonly sourced from adipose tissue, bone marrow and umbilical cord, have been widely used in many medical conditions due to their therapeutic potential. Yet, the still limited understanding of the underlying mechanisms of action hampers clinical translation. Clinical potency can vary considerably depending on tissue source, donor attributes, but importantly, also culture conditions. Lack of standard procedures hinders inter-study comparability and delays the progression of the field. The aim of this study was A-to assess the impact on MSC characteristics when different laboratories performed analysis on the same MSC material using harmonised culture conditions and B-to understand source-specific differences.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Three independent institutions performed a head-to-head comparison of human-derived adipose (A-), bone marrow (BM-), and umbilical cord (UC-) MSCs using harmonised culture conditions. In each centre, cells from one specific tissue source were isolated and later distributed across the network to assess their biological properties, including cell expansion, immune phenotype, and tri-lineage differentiation (part A). To assess tissue specific function, angiogenic and immunomodulatory properties and the <jats:italic>in vivo</jats:italic> biodistribution were compared in one expert lab (part B).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>By implementing a harmonised manufacturing workflow, we obtained largely reproducible results across three independent laboratories in part A of our study. Unique growth patterns and differentiation potential were observed for each tissue source, with similar trends observed between centres. Immune phenotyping verified expression of typical MSC surface markers and absence of contaminating surface markers. Depending on the established protocols in the different laboratories, quantitative data varied slightly. Functional experiments in part B concluded that conditioned media from BM-MSCs significantly enhanced tubulogenesis and endothelial migration <jats:italic>in vitro</jats:italic>. In contrast, immunomodulatory studies reported superior immunosuppressive abilities for A-MSCs. Biodistribution studies in healthy mice showed lung entrapment after administration of all three types of MSCs, with a significantly faster clearance of BM-MSCs.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These results show the heterogeneous behaviour and regenerative properties of MSCs as a reflection of intrinsic tissue-origin properties while providing evidence that the use of standardised culture procedures can reduce but not eliminate inter-lab and operator differences.</jats:p></jats:sec><jats:sec><jats:title>Highlights</jats:title><jats:p>In this study, we have:</jats:p><jats:list list-type="simple"><jats:list-item><jats:label>-</jats:label><jats:p>Provided a harmonised manufacturing workflow that has demonstrated reproducible results across three independent laboratories when expanding MSCs.</jats:p></jats:list-item><jats:list-item><jats:label>-</jats:label><jats:p>Defined a multi-assay matrix capable of identifying functional differences in terms of angiogenesis, wound healing abilities and immunosuppressive properties.</jats:p></jats:list-item><jats:list-item><jats:label>-</jats:label><jats:p>Demonstrated similar <jats:italic>in vivo</jats:italic> biodistribution properties regardless of cell origin.</jats:p></jats:list-item></jats:list></jats:sec>

Item Type: Preprint
Uncontrolled Keywords: 3206 Medical Biotechnology, 32 Biomedical and Clinical Sciences, 40 Engineering, 4003 Biomedical Engineering, Stem Cell Research, Transplantation, Cardiovascular
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 07 Dec 2022 12:22
Last Modified: 18 Jul 2024 18:24
DOI: 10.1101/2022.09.14.507944
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