International Journal of Stem Cells

Korean Society for Stem Cell Research (한국줄기세포학회)
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Enhanced Anti-Cancer Effects of Conditioned Medium from Hypoxic Human Umbilical Cord-Derived Mesenchymal Stem Cells

  • Han, Kyu-Hyun (Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Ae-Kyeong (Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jeong, Gun-Jae (Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jeon, Hye Ran (Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Bhang, Suk Ho (Sungkyunkwan University School of Chemical Engineering) ;
  • Kim, Dong-ik (Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • Received : 2019.01.02
  • Accepted : 2019.03.06
  • Published : 2019.07.31
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Abstract

Background and Objectives: There have been contradictory reports on the pro-cancer or anti-cancer effects of mesenchymal stem cells. In this study, we investigated whether conditioned medium (CM) from hypoxic human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) (H-CM) showed enhanced anti-cancer effects compared with CM from normoxic hUC-MSCs (N-CM). Methods and Results: Compared with N-CM, H-CM not only strongly reduced cell viability and increased apoptosis of human cervical cancer cells (HeLa cells), but also increased caspase-3/7 activity, decreased mitochondrial membrane potential (MMP), and induced cell cycle arrest. In contrast, cell viability, apoptosis, MMP, and cell cycle of human dermal fibroblast (hDFs) were not significantly changed by either CM whereas caspase-3/7 activity was decreased by H-CM. Protein antibody array showed that activin A, Beta IG-H3, TIMP-2, RET, and IGFBP-3 were upregulated in H-CM compared with N-CM. Intracellular proteins that were upregulated by H-CM in HeLa cells were represented by apoptosis and cell cycle arrest terms of biological processes of Gene Ontology (GO), and by cell cycle of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In hDFs, negative regulation of apoptosis in biological process of GO and PI3K-Akt signaling pathway of KEGG pathways were represented. Conclusions: H-CM showed enhanced anti-cancer effects on HeLa cells but did not influence cell viability or apoptosis of hDFs and these different effects were supported by profiling of secretory proteins in both kinds of CM and intracellular signaling of HeLa cells and hDFs.

Keywords

Acknowledgement

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (NRF-2018M3A9E2023255).

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