Multiomics Evaluation of Human Fat-Derived Mesenchymal Stem Cells on an Osteobiologic Nanocomposite

Multiomics Evaluation of Human Fat-Derived Mesenchymal Stem Cells on an Osteobiologic Nanocomposite
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DOI:
10.1089/biores.2020.0005
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发表时间:
2020-02-01
影响因子:
--
通讯作者:
Dhar, Madhu
Dhar, Madhu
中科院分区:
其他
文献类型:
--
作者:
Bow, Austin;Jackson, Bailey;Dhar, Madhu

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有效的骨修复技术一直是骨组织工程领域的主要焦点。我们以前制造和研究的纳米复合材料组成的聚氨酯,纳米羟基磷灰石,脱细胞骨颗粒,这表明骨生物学特性。为了评估这种生物材料的潜在机制,使用转录组学和代谢组学分析的组合方法评估人脂肪源性间充质干细胞接种的支架。通过液相色谱-质谱法测量的成骨和信号转导聚合酶链反应阵列和小分子丰度的数据,使用集成分子通路水平分析、注释数据库、可视化和集成发现以及PatisusPathDB在线工具进行交叉检查,以生成支架影响通路的基本集合。结果表明关键成骨细胞粘附细胞信号传导标志物的上调,并表明Hedgehog和Wnt信号传导途径是支架设计的骨生物学机制的主要候选者。互补代谢物如抗坏血酸的检测进一步表明支架产生复杂的细胞环境,促进细胞附着和随后的骨分化。
Effective graft technologies for bone repair have been a primary focus in the field of bone tissue engineering. We have previously fabricated and examined a nanocomposite composed of polyurethane, nano-hydroxyapatite, and decellularized bone particles, which demonstrated osteobiologic characteristics. To evaluate the underlying mechanisms of this biomaterial, human adipose-derived mesenchymal stem cell seeded scaffolds were assessed using a combinatorial approach of transcriptomic and metabolomic analyses. Data from osteogenic and signal transduction polymerase chain reaction arrays and small molecule abundances, measured through liquid chromatography-mass spectrometry, were cross-examined using Integrated Molecular Pathway Level Analysis, Database for Annotation, Visualization, and Integrated Discovery, and ConsensusPathDB online tools to generate a fundamental collection of scaffold-influenced pathways. Results demonstrated upregulation of key osteogenic, cellular adhesion cell signaling markers and indicated that Hedgehog and Wnt signaling pathways were primary candidates for the osteobiologic mechanisms of the scaffold design. The detection of complimentary metabolites, such as ascorbate, further indicates that scaffolds generate intricate cellular environments, promoting cell attachment and subsequent osteodifferentiation.