Conditioned medium from normoxia (WJMSCs-norCM) and hypoxia-treated WJMSCs (WJMSCs-hypoCM) in inhibiting cancer cell proliferation

Abstract

Mesenchymal stem cells (MSCs) have unique properties, including high proliferation rates, self-renewal, multilineage differentiation ability, wide multipotency, hypoimmunogenicity, noninduction of teratomas, and anticancer properties. MSCs can be isolated from embryonic and extraembryonic tissues as well as adult organs. Human Wharton's jelly stem cell-conditioned medium possesses anticancer properties and inhibits the growth of solid tumors. Lower oxygen concentration or hypoxic condition can increase the proliferation of MSCs, but there are no differences in surface markers. We determined the osteocyte, chondrocyte, and adipocyte differentiation of normoxic WJMSCs (nor-WJMSCs) and hypoxic 2.5%, hypoxic 5% (hypo-WJMSCs); from a different passage (P4 and P8), we determined the inhibitory effect of WJMSCs-norCM and WJMSCs-hypoCM on the proliferation of human cancer cells including cervical (HeLa), liver (HepG2), prostate (pc3), ovarian (skov3), and oral squamous (hsc3) cancer cell lines compared to normal cells including mouse fibroblast (NIH3T3), human fibroblast, and human mesenchymal stem cells (hMSCs). Surfacer marker expression of nor-WJMSCs-and hypo-WJMSCs from P4 and P8 were >95% for CD90, CD73 and CD105 and <2% for CD14, CD19, CD34, CD45, and HLDA-II. Nor-WJMSCs and hypo-WJMSCs from P4 and P8 underwent differentiation to osteocyte, chondrocyte, and adipocyte. WJMSCs-norCM and WJMSCs-hypoCM could inhibit proliferation of various cancer cell lines with minimum inhibitory concentration (IC₅₀) 51.690–81.440% and cause low inhibition of the normal cells with IC50 136.290–185.339%. WJMSCs-norCM and WJMSCs-hypoCM were not cytotoxic toward normal cells. Nor-WJMSCs and hypo-WJMSCs from P4 and P8 showed no significant differences in MSC surface marker expression or differentiation. WJMSCs-norCM and WJMSCs-hypoCM could inhibit proliferation in various cancer cell lines, and were safe for normal cells.