Human Wharton's Jelly-Derived Stem Cells Display a Distinct Immunomodulatory and Proregenerative Transcriptional Signature Compared to Bone Marrow-Derived Stem Cells.

Journal: Stem cells and development
PMID: 29267140

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 BM-MSC 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.

Authors

  • Raf Donders
    1 Biomedical Research Institute, Hasselt University , Diepenbeek, Belgium .
  • Jeroen F J Bogie
    1 Biomedical Research Institute, Hasselt University , Diepenbeek, Belgium .
  • Stylianos Ravanidis
    1 Biomedical Research Institute, Hasselt University , Diepenbeek, Belgium .
  • Pascal Gervois
    1 Biomedical Research Institute, Hasselt University , Diepenbeek, Belgium .
  • Marjan Vanheusden
    1 Biomedical Research Institute, Hasselt University , Diepenbeek, Belgium .
  • Raphaël Marée
    2 University of Liège , GIGA Bioinformatics Core Facility, Liège, Belgium .
  • Marie Schrynemackers
    Department of EE and CS & GIGA-R, University of Liège, Belgium. marie.schrynemackers@ulg.ac.be.
  • Hubert J M Smeets
    3 Maastricht UMC+, Department of Genetics and Cell Biology, Research School GROW and CARIM , Maastricht, the Netherlands .
  • Jef Pinxteren
    4 ReGenesys BVBA , Bio-Incubator Leuven, Heverlee, Belgium .
  • Kristel Gijbels
    4 ReGenesys BVBA , Bio-Incubator Leuven, Heverlee, Belgium .
  • Sara Walbers
    4 ReGenesys BVBA , Bio-Incubator Leuven, Heverlee, Belgium .
  • Robert W Mays
    5 Department of Regenerative Medicine, Athersys, Inc. , Cleveland, Ohio.
  • Robert Deans
    5 Department of Regenerative Medicine, Athersys, Inc. , Cleveland, Ohio.
  • Ludo Van Den Bosch
    6 KU Leuven, Laboratory of Neurobiology, Experimental Neurology and VIB, Center for Brain & Disease , Leuven, Belgium .
  • Piet Stinissen
    1 Biomedical Research Institute, Hasselt University , Diepenbeek, Belgium .
  • Ivo Lambrichts
    1 Biomedical Research Institute, Hasselt University , Diepenbeek, Belgium .
  • Wilfried Gyselaers
    1 Biomedical Research Institute, Hasselt University , Diepenbeek, Belgium .
  • Niels Hellings
    1 Biomedical Research Institute, Hasselt University , Diepenbeek, Belgium .

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