Human Wharton's jelly stem cells, its conditioned medium and cell-free lysate inhibit the growth of human lymphoma cells.
Several groups have reported that primitive mesenchymal stem cells from the gelatinous matrix of the Wharton's jelly of the human umbilical cord (hWJSCs) possess tumoricidal properties and inhibit the growth of solid tumours such as human mammary carcinoma, ovarian carcinoma and osteosarcoma. This unique characteristic led to the hypothesis that hWJSCs serve as a natural defence against migrating cancer cells from mother to fetus thus explaining why tumorigenesis in the fetus is rare. However, it is not known whether non-solid malignant hematopoietic cells are also inhibited by hWJSCs and what the exact tumoricidal mechanisms are. We therefore evaluated the influence of hWJSCs and its extracts on Burkitt's lymphoma cells. Cell proliferation (BrdU and Ki67+), viability (MTT) and cell death (Annexin V-Propidium iodide and live/dead) assays showed significant inhibition of lymphoma cell growth after 48 h exposure to hWJSCs or its extracts compared to controls. Increased cell death was observed at sub-G1 and S and decreased proliferation at G2/M phases of the mitotic cycle. Superoxide dismutase and hydrogen peroxide activity were significantly increased and glutathione peroxidase significantly decreased in treated lymphoma cells. Time lapse imaging and confocal z-stack images showed yellow fluorescent in situ hybridization (FISH) signals of lymphoma cell Y chromosomes within the cytoplasm of female red labelled hWJSCs. We hypothesize that the growth of lymphoma cells is inhibited by the molecules secreted by hWJSCs that use oxidative stress pathways to induce cell death followed by engulfment of the apoptotic remains of the lymphoma cells by the hWJSCs.
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Kent Ridge, Singapore, Singapore, 119228.
Hao Daniel
HD
Lin
Chui Yee
CY
Fong
Arijit
A
Biswas
Mahesh
M
Choolani
Ariff
A
Bongso
D017209:Apoptosis; D001853:Bone Marrow; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006801:Humans; D008223:Lymphoma / Q000473:pathology / Q000517:prevention & control*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D018384:Oxidative Stress; D012867:Skin / Q000166:cytology; D014470:Umbilical Cord / Q000166:cytology*; D059631:Wharton Jelly / Q000166:cytology*
D017077:Culture Media, Conditioned