Int J Stem Cells.  2019 Jul;12(2):291-303. 10.15283/ijsc19002.

Enhanced Anti-Cancer Effects of Conditioned Medium from Hypoxic Human Umbilical Cord–Derived Mesenchymal Stem Cells

Affiliations
  • 1Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. dikim@skku.edu
  • 2Sungkyunkwan University School of Chemical Engineering, Suwon, Korea.

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.

Keyword

Anti-cancer; Conditioned medium; Fibroblasts; Hypoxia; Mesenchymal stem cells

MeSH Terms

Activins
Anoxia
Apoptosis
Biological Processes
Cell Cycle
Cell Cycle Checkpoints
Cell Survival
Culture Media, Conditioned*
Fibroblasts
Gene Ontology
Genome
HeLa Cells
Humans*
Insulin-Like Growth Factor Binding Protein 3
Membrane Potential, Mitochondrial
Mesenchymal Stromal Cells*
Tissue Inhibitor of Metalloproteinase-2
Uterine Cervical Neoplasms
Activins
Culture Media, Conditioned
Insulin-Like Growth Factor Binding Protein 3
Tissue Inhibitor of Metalloproteinase-2
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