Hypoxia influences the effects of magnesium degradation products on the interactions between endothelial and mesenchymal stem cells

Abstract

Biodegradable materials like well-documented Magnesium (Mg) are promising for their biocompatibility and tissue regeneration. Since Mg degradation is reported to be oxygen related, the effects of Mg were hypothesised to be influenced by oxygen. As two vital components of bone marrow, endothelial cells (EC) and mesenchymal stem cells (MSC), their interactions represent high scientific interest for tissue engineering and biodegradable Mg application. Human umbilical cord perivascular (HUCPV) and umbilical vein endothelial cell (HUVEC) were selected as sources of MSC and EC, respectively. Two types of coculture models were established to represent different phases of MSC-EC interaction: (i) where cells were physically separated thanks to a transwell and (ii) where cells were allowed to have heterotypic cellular contacts. Cell migration, gene, cytokines, and proliferation were investigated in HUCPV-HUVEC coculture using DNA, flow cytometry, wound healing assay, semi-quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). Mg degradation products increased HUCPV migration in transwell under hypoxia. Oxygen tension changed the gene regulation of migratory, angiogenetic or osteogenic regulators. Under contacting coculture and hypoxia, Mg degradation products remarkably increased cytokines (e.g., c-c motif chemokine ligand 2 and vascular endothelial growth factor) and MSC mineralisation. Mg degradation products decreased and increased the MSC proliferation in transwell and in heterotypic-contact coculture, respectively. In summary, this study indicates the roles of low oxygen and heterotypic contact to effects of Mg materials facilitating HUVEC and HUCPV. STATEMENT OF SIGNIFICANCE.

Keywords: Coculture; Endothelial cell; Engineered tissue; Hypoxia; Magnesium; Mesenchymal stem cell; Metallic biodegradable material.