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Title: | Human Wharton's Jelly-Derived Stem Cells Display a Distinct Immunomodulatory and Proregenerative Transcriptional Signature Compared to Bone Marrow-Derived Stem Cells | Authors: | DONDERS, Raf BOGIE, Jeroen RAVANIDIS, Stelios GERVOIS, Pascal VANHEUSDEN, Marjan Marée, Raphaël Schrynemackers, Marie Smeets, Hubert J.M. Pinxteren, Jef Gijbels, Kristel Walbers, Sara Mays, Robert W. Deans, Robert Van Den Bosch, Ludo STINISSEN, Piet LAMBRICHTS, Ivo GYSELAERS, Wilfried HELLINGS, Niels |
Issue Date: | 2018 | Source: | Stem cells and development, 27(2), p. 65-84 | Abstract: | Mesenchymal stromal cells (MSCs) are multipotent stem cells with immunosuppressive and trophic support functions. While MSCs from different sources frequently display a similar appearance in culture, they often show differences in their surface marker and gene expression profiles. Although bone marrow is considered the ‘‘gold standard’’ tissue to isolate classical MSCs (BM-MSC), MSC-like cells are currently also derived from more easily accessible extra-embryonic tissues such as the umbilical cord. In this study, we defined the best way to isolate MSCs from the Wharton’s jelly of the human umbilical cord (WJ-MSC) and assessed the mesenchymal and immunological phenotype of BM-MSC and WJ-MSC. Moreover, the gene expression profile of established WJ-MSC cultures was compared to two different bone marrow-derived stem cell populations (BM-MSC and multipotent adult progenitor cells or MAPC). We observed that explant culturing of Wharton’s jelly matrix is superior to collagenase tissue digestion for obtaining mesenchymal-like cells, with explant isolated cells displaying increased expansion potential. While being phenotypically similar to adult MSCs, WJ-MSC show a different gene expression profile. Gene ontology analysis revealed that genes associated with cell adhesion, proliferation, and immune system functioning are enriched in WJ-MSC. In vivo transplantation confirms their immune modulatory effect on T cells, similar to BMMSC and MAPC. Furthermore, WJ-MSC intrinsically overexpress genes involved in neurotrophic support and their secretome induces neuronal maturation of SH-SY5Y neuroblastoma cells to a greater extent than BM-MSC. This signature makes WJ-MSC an attractive candidate for cell-based therapy in neurodegenerative and immune-mediated central nervous system disorders such as multiple sclerosis, Parkinson’s disease, or amyotrophic lateral sclerosis. | Keywords: | umbilical cord; microarray; MAPC; MSC; neurotrophic factors; immune modulation | Document URI: | http://hdl.handle.net/1942/25505 | ISSN: | 1547-3287 | e-ISSN: | 1557-8534 | DOI: | 10.1089/scd.2017.0029 | ISI #: | 000418565900001 | Rights: | (C) Mary Ann Liebert, Inc. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2019 |
Appears in Collections: | Research publications |
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scd.2017.0029.pdf Restricted Access | Published version | 888.54 kB | Adobe PDF | View/Open Request a copy |
draft for resubmission check.pdf | Non Peer-reviewed author version | 2.38 MB | Adobe PDF | View/Open |
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