Harmonised culture procedures minimise but do not eliminate mesenchymal stromal cell donor and tissue variability in a decentralised multicentre manufacturing approach

Bibliographic Details
Title:	Harmonised culture procedures minimise but do not eliminate mesenchymal stromal cell donor and tissue variability in a decentralised multicentre manufacturing approach
Authors:	Sandra Calcat-i-Cervera, Erika Rendra, Eleonora Scaccia, Francesco Amadeo, Vivien Hanson, Bettina Wilm, Patricia Murray, Timothy O’Brien, Arthur Taylor, Karen Bieback
Source:	Stem Cell Research & Therapy, Vol 14, Iss 1, Pp 1-17 (2023)
Publisher Information:	BMC, 2023.
Publication Year:	2023
Collection:	LCC:Medicine (General) LCC:Biochemistry
Subject Terms:	Mesenchymal stromal cells (MSCs), Tissue source, Multicentre comparison, Manufacturing, Harmonisation, Angiogenesis, Medicine (General), R5-920, Biochemistry, QD415-436
More Details:	Abstract Background 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. Methods 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 in vivo biodistribution were compared in one expert lab (part B). Results 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 in vitro. 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. Conclusion 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 harmonised culture procedures can reduce but do not eliminate inter-lab and operator differences.
Document Type:	article
File Description:	electronic resource
Language:	English
ISSN:	1757-6512
Relation:	https://doaj.org/toc/1757-6512
DOI:	10.1186/s13287-023-03352-1
Access URL:	https://doaj.org/article/6e677206ca534025a0e639dd69a926f4
Accession Number:	edsdoj.6e677206ca534025a0e639dd69a926f4
Database:	Directory of Open Access Journals
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More Details
ISSN:	17576512
DOI:	10.1186/s13287-023-03352-1
Published in:	Stem Cell Research & Therapy
Language:	English