Nguyen TY*, Liew CG, Liu H (2013) An
In Vitro Mechanism Study on the Proliferation and Pluripotency of Human
Embryonic Stems Cells in Response to Magnesium Degradation. PLoS ONE 8(10):
e76547.
doi:10.1371/journal.pone.0076547 Magnesium (Mg) is a promising biodegradable metallic material for
applications in cellular/tissue engineering and biomedical
implants/devices. To advance clinical translation of Mg-based
biomaterials, we investigated the effects and mechanisms of Mg
degradation on the proliferation and pluripotency of human embryonic
stem cells (hESCs). We used hESCs as the in vitro model system
to study cellular responses to Mg degradation because they are sensitive
to toxicants and capable of differentiating into any cell types of
interest for regenerative medicine. In a previous study when hESCs were
cultured in vitro with either polished metallic Mg (99.9%
purity) or pre-degraded Mg, cell death was observed within the first 30
hours of culture. Excess Mg ions and hydroxide ions induced by Mg
degradation may have been the causes for the observed cell death; hence,
their respective effects on hESCs were investigated for the first time
to reveal the potential mechanisms. For this purpose, the mTeSR®1 hESC
culture media was either modified to an alkaline pH of 8.1 or
supplemented with 0.4–40 mM of Mg ions. We showed that the initial
increase of media pH to 8.1 had no adverse effect on hESC proliferation.
At all tested Mg ion dosages, the hESCs grew to confluency and retained
pluripotency as indicated by the expression of OCT4, SSEA3, and SOX2.
When the supplemental Mg ion dosages increased to greater than 10 mM,
however, hESC colony morphology changed and cell counts decreased. These
results suggest that Mg-based implants or scaffolds are promising in
combination with hESCs for regenerative medicine applications, providing
their degradation rate is moderate. Additionally, the hESC culture
system could serve as a standard model for cytocompatibility studies of
Mg in vitro, and an identified 10 mM critical dosage of Mg ions
could serve as a design guideline for safe degradation of Mg-based
implants/scaffolds. |
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