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

Raf Donders, Jeroen F. J. Bogie, Stylianos Ravanidis, Pascal Gervois, Marjan Vanheusden, Raphael Maree, Marie Schrynemackers, Hubert J. M. Smeets, Jef Pinxteren, Kristel Gijbels, Sara Walbers, Robert W. Mays, Robert Deans, Ludo Van Den Bosch, Piet Stinissen, Ivo Lambrichts, Wilfried Gyselaers, Niels Hellings*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

62 Citations (Web of Science)

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((R))). 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.
Original languageEnglish
Pages (from-to)65-84
Number of pages20
JournalStem Cells and Development
Volume27
Issue number2
DOIs
Publication statusPublished - 1 Jan 2018

Keywords

  • umbilical cord
  • microarray
  • MAPC
  • MSC
  • neurotrophic factors
  • immune modulation
  • HUMAN UMBILICAL-CORD
  • ADULT PROGENITOR CELLS
  • MESENCHYMAL STROMAL CELLS
  • CLINICAL-APPLICATIONS
  • PHENOTYPIC CHARACTERIZATION
  • DIFFERENTIATION CAPACITY
  • REGENERATIVE MEDICINE
  • CULTURE-CONDITIONS
  • ISCHEMIC-STROKE
  • GENE-EXPRESSION

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