Hypoxia and Amino Acid Supplementation Synergistically Promote the Osteogenesis of Human Mesenchymal Stem Cells on Silk Protein Scaffolds
Hypoxia and Amino Acid Supplementation Synergistically Promote the Osteogenesis of Human Mesenchymal Stem Cells on Silk Protein Scaffolds
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DOI：
10.1089/ten.tea.2010.0302
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发表时间：
2010-12-01
影响因子：
4.1
通讯作者：
Kaplan, David L.
中科院分区：
文献类型：
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作者：
Sengupta, Sejuti;Park, Sang-Hyug;Kaplan, David L.
定制组织工程策略以满足患者和组织特异性骨再生需求，可以改善临床结果。作为实现这一目标的一步，当改变骨形成过程的输入时，评估成骨结果和代谢参数。在成骨分化培养基中接种人间充质干细胞的丝蛋白支架用于研究不同氨基酸（赖氨酸和脯氨酸）浓度和氧水平条件下的体外成骨作用。对细胞进行评估，以探究微环境如何影响代谢途径以及成骨作用。在体外培养过程中，在低（5%）氧气与高赖氨酸和脯氨酸浓度相结合的情况下，发现最有利的成骨结果。同一组培养条件还显示出最高的葡萄糖消耗、乳酸合成和某些氨基酸消耗率。根据这些结果和已知途径，得出了一个整体代谢模型，该模型表明赖氨酸和脯氨酸补充剂以及低氧水平（5%）可调节胶原基质合成，从而调节成骨率。这项研究为代谢、修复部位和组织工程方法之间的患者和组织特异性匹配奠定了基础，以优化骨再生。
Tailoring tissue engineering strategies to match patient-and tissue-specific bone regeneration needs offers to improve clinical outcomes. As a step toward this goal, osteogenic outcomes and metabolic parameters were assessed when varying inputs into the bone formation process. Silk protein scaffolds seeded with human mesenchymal stem cells in osteogenic differentiation media were used to study in vitro osteogenesis under varied conditions of amino acid (lysine and proline) concentration and oxygen level. The cells were assessed to probe how the microenvironment impacted metabolic pathways and thus osteogenesis. The most favorable osteogenesis outcomes were found in the presence of low (5%) oxygen combined with high lysine and proline concentrations during in vitro cultivation. This same set of culture conditions also showed the highest glucose consumption, lactate synthesis, and certain amino acid consumption rates. On the basis of these results and known pathways, a holistic metabolic model was derived which shows that lysine and proline supplements as well as low (5%) oxygen levels regulate collagen matrix synthesis and thereby rates of osteogenesis. This study establishes early steps toward a foundation for patient-and tissue-specific matches between metabolism, repair site, and tissue engineering approaches toward optimized bone regeneration.