TY - JOUR
T1 - Human Wharton's Jelly-Derived Stem Cells Display a Distinct Immunomodulatory and Proregenerative Transcriptional Signature Compared to Bone Marrow-Derived Stem Cells
AU - Donders, Raf
AU - Bogie, Jeroen F. J.
AU - Ravanidis, Stylianos
AU - Gervois, Pascal
AU - Vanheusden, Marjan
AU - Maree, Raphael
AU - Schrynemackers, Marie
AU - Smeets, Hubert J. M.
AU - Pinxteren, Jef
AU - Gijbels, Kristel
AU - Walbers, Sara
AU - Mays, Robert W.
AU - Deans, Robert
AU - Van Den Bosch, Ludo
AU - Stinissen, Piet
AU - Lambrichts, Ivo
AU - Gyselaers, Wilfried
AU - Hellings, Niels
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - umbilical cord
KW - microarray
KW - MAPC
KW - MSC
KW - neurotrophic factors
KW - immune modulation
KW - HUMAN UMBILICAL-CORD
KW - ADULT PROGENITOR CELLS
KW - MESENCHYMAL STROMAL CELLS
KW - CLINICAL-APPLICATIONS
KW - PHENOTYPIC CHARACTERIZATION
KW - DIFFERENTIATION CAPACITY
KW - REGENERATIVE MEDICINE
KW - CULTURE-CONDITIONS
KW - ISCHEMIC-STROKE
KW - GENE-EXPRESSION
U2 - 10.1089/scd.2017.0029
DO - 10.1089/scd.2017.0029
M3 - Article
SN - 1547-3287
VL - 27
SP - 65
EP - 84
JO - Stem Cells and Development
JF - Stem Cells and Development
IS - 2
ER -