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

被引:19
作者
Calcat-i-Cervera, Sandra [1 ]
Rendra, Erika [2 ]
Scaccia, Eleonora [2 ]
Amadeo, Francesco [3 ,4 ,5 ]
Hanson, Vivien [4 ]
Wilm, Bettina [3 ,5 ]
Murray, Patricia [3 ,5 ]
O'Brien, Timothy [1 ,6 ]
Taylor, Arthur [3 ,5 ]
Bieback, Karen [2 ,7 ]
机构
[1] Univ Galway, Regenerat Med Inst Remed, Coll Med, Sch Med, Galway, Ireland
[2] Heidelberg Univ, Inst Transfus Med & Immunol, Med Fac Mannheim, German Red Cross Blood Serv, Friedrich Ebert Str 107, D-68167 Mannheim, Hessen, Germany
[3] Univ Liverpool, Dept Mol Physiol & Cell Signalling, Liverpool, Lancashire, England
[4] NHS Blood & Transplant, Cellular Therapies Lab, Liverpool, Lancashire, England
[5] Univ Liverpool, Ctr Preclin Imaging, Liverpool, Lancashire, England
[6] Univ Galway, SFI Res Ctr Med Devices, CURAM, Galway, Ireland
[7] Heidelberg Univ, Mannheim Inst Innate Immunoscience, Med Fac Mannheim, Mannheim, Germany
关键词
Mesenchymal stromal cells (MSCs); Tissue source; Multicentre comparison; Manufacturing; Harmonisation; Angiogenesis; Immunomodulation; In vivo distribution; UMBILICAL-CORD BLOOD; STEM-CELLS; BONE-MARROW; INTERNATIONAL-SOCIETY; THERAPY; CRYOPRESERVATION; SERUM;
D O I
10.1186/s13287-023-03352-1
中图分类号
Q813 [细胞工程];
学科分类号
摘要
BackgroundMesenchymal 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.MethodsThree 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).ResultsBy 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.ConclusionThese 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.
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页数:17
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