title: Human umbilical cord Wharton's jelly mesenchymal stem cells do not transform to tumor-associated fibroblasts in the presence of breast and ovarian cancer cells unlike bone marrow mesenchymal stem cells.
abstract: Human bone marrow mesenchymal stem cells (hBMMSCs) were shown to transform into tumor-associated fibroblasts (TAFs) when in the vicinity of breast cancer tumors and played an important role in tumor enhancement and metastasis. In early human development MSCs migrating from the yolk sac and aorta-gonad-mesonephros (AGM) via the umbilical cord to the placenta and back to the fetal bone marrow were shown to get trapped in the gelatinous Wharton's jelly of the umbilical cord. The common origin of the Wharton's jelly MSCs and the finally homed hBMMSCs prompted us to evaluate whether hWJSCs are also involved in TAF transformation. hWJSCs and hBMMSCs were grown in the presence of breast and ovarian cancer cell conditioned medium (MDA-TCM, TOV-TCM) for 30 days. No changes were observed in the hWJSCs but the hBMMSCs transformed from short to thin long fibroblasts, their proliferation rates increased and CD marker expression decreased. The transformed hBMMSCs showed positive staining for the tumor-associated markers FSP, VEGF, EGF, and Tn-C. Real-time PCR and multiplex luminex bead analysis showed upregulation of TAF-related genes (FSP, FAP, Tn-C, Tsp-1, EGF, bFGF, IL-6, α-SMA, VEGF, and TGF-β) for hBMMSCs with low expression for hWJSCs. The luciferase assay showed that hWJSCs previously exposed to MDA-TCM or TOV-TCM had no stimulatory growth effect on luciferase-tagged MDA or TOV cells unlike hBMMSCs. The results confirmed that hWJSCs do not transform to the TAF phenotype and may therefore not be associated with enhanced growth of solid tumors making them a safe MSC for cell based therapies.
authors.affiliation: Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Kent Ridge 119074, Singapore.
authors.forename: Arjunan
authors.initials: A
authors.lastname: Subramanian
authors.forename: Gan
authors.initials: G
authors.lastname: Shu-Uin
authors.forename: Ngo
authors.initials: N
authors.lastname: Kae-Siang
authors.forename: Kalamegam
authors.initials: K
authors.lastname: Gauthaman
authors.forename: Arijit
authors.initials: A
authors.lastname: Biswas
authors.forename: Mahesh
authors.initials: M
authors.lastname: Choolani
authors.forename: Ariff
authors.initials: A
authors.lastname: Bongso
authors.forename: Fong
authors.initials: F
authors.lastname: Chui-Yee
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D001943:Breast Neoplasms / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D010641:Phenotype; D014470:Umbilical Cord; D059631:Wharton Jelly / Q000166:cytology*
chemical_list: D017077:Culture Media, Conditioned