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Biological differences between adult and perinatal human mesenchymal stromal cells and their impact on the manufacturing processes

Pedro Silva Couto, Dale J. Stibbs, Marco C. Rotondi, Rana Khalife, Dennis Wolf, Yasuhiro Takeuchi, Qasim A. Rafiq

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Abstract

The biological properties of human mesenchymal stromal cells (hMSCs) have been explored in over a thousand clinical trials in the last decade. Although hMSCs can be isolated from multiple sources, the degree ofbiological similarity between cell populations from these sources remains to be determined. A comparativestudy was performed investigating the growth kinetics and functionality of hMSCs isolated from adipose tissue (AT), bone marrow (BM) and umbilical cord tissue (UCT) expanded in monolayer over five passages.Adult hMSCs (AT, BM) had a slower proliferation ability than the UCT-hMSCs, with no apparent differencesin their glucose consumption profile. BM-hMSCs produced higher concentrations of endogenous vascularendothelial growth factor (VEGF) compared to AT- and UCT-hMSCs. This study also revealed that UCT-hMSCswere more efficiently transduced by a lentiviral vector carrying a VEGF gene than their adult counterparts.Following cellular immunophenotypic characterization, no differences across the sources were found in theexpression levels of the typical markers used to identify hMSCs. This work established a systematic approachfor cell source selection depending on the hMSC’s intended clinical application.
Original languageEnglish
Pages (from-to)1429-1441
Number of pages13
JournalCytotherapy
Volume26
Issue number11
Early online date30 May 2024
DOIs
Publication statusPublished - 30 Nov 2024

Data Availability Statement

All data generated or analyzed during this study is included in this published article.

Funding

The work presented in this manuscript was supported by a United Kingdom Research and Innovation (UKRI) Engineering and Physical Sciences Research Council (EPSRC) Fellowship grant awarded to Professor Qasim Rafiq (EP/V058266/1).

FundersFunder number
Engineering and Physical Sciences Research Council

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