An in vitro mechanism study on the proliferation and pluripotency of human embryonic stems cells in response to magnesium degradation.
An in vitro mechanism study on the proliferation and pluripotency of human embryonic stems cells in response to magnesium degradation.
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DOI：
10.1371/journal.pone.0076547
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Nguyen TY;Liew CG;Liu H
镁（Mg）是一种在细胞/组织工程和生物医学植入物/装置中有应用前景的可生物降解金属材料。为了促进镁基生物材料的临床转化，我们研究了镁降解对人胚胎干细胞（hESCs）增殖和多能性的影响和机制。我们使用人胚胎干细胞作为体外模型系统来研究细胞对镁降解的反应，因为它们对毒物敏感，并且能够分化成再生医学所关注的任何细胞类型。在先前的研究中，当用抛光的金属Mg（99.9%纯度）或预降解的Mg体外培养hESC时，在培养的前30小时内观察到细胞死亡。过量的镁离子和镁降解诱导的氢氧根离子可能是观察到的细胞死亡的原因，因此，它们各自对hESC的影响首次进行了研究，以揭示潜在的机制。为此目的，将mTeSR®1 hESC培养基改性至8.1的碱性pH或补充有0.4-40 mM的Mg离子。我们发现，初始增加培养基pH值至8.1对hESC增殖没有不利影响。在所有测试的Mg离子剂量下，hESC生长至汇合并保持多能性，如OCT 4、SSEA 3和SOX 2的表达所示。然而，当补充Mg离子剂量增加到大于10 mM时，hESC集落形态发生变化，细胞计数减少。这些结果表明，Mg基植入物或支架与hESC组合用于再生医学应用是有希望的，只要它们的降解速率是中等的。此外，人胚胎干细胞培养系统可以作为一个标准的模型，镁在体外的细胞相容性研究，并确定了10 mM的镁离子的临界剂量可以作为镁基植入物/支架的安全降解的设计指南。
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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