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人脂肪来源间充质干细胞在骨生物纳米复合材料上的多组学评估

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

作者信息

Bow Austin, Jackson Bailey, Griffin Christopher, Howard Sara, Castro Hector, Campagna Shawn, Biris Alexandru S, Anderson David E, Bourdo Shawn, Dhar Madhu

机构信息

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee.

Center for Integrative Nanotechnology Sciences, University of Arkansas at Little Rock, Little Rock, Arkansas.

出版信息

Biores Open Access. 2020 Feb 21;9(1):37-50. doi: 10.1089/biores.2020.0005. eCollection 2020.

Abstract

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.

摘要

有效的骨修复移植技术一直是骨组织工程领域的主要研究重点。我们之前制备并研究了一种由聚氨酯、纳米羟基磷灰石和脱细胞骨颗粒组成的纳米复合材料,该材料具有骨生物学特性。为了评估这种生物材料的潜在机制,我们使用转录组学和代谢组学分析的组合方法对接种了人脂肪来源间充质干细胞的支架进行了评估。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数据以及小分子丰度,使用综合分子通路水平分析、注释、可视化和综合发现数据库以及ConsensusPathDB在线工具进行交叉检查,以生成受支架影响的通路的基本集合。结果表明关键成骨、细胞粘附细胞信号标记物上调,并表明刺猬信号通路和Wnt信号通路是支架设计骨生物学机制的主要候选通路。对诸如抗坏血酸盐等互补代谢物的检测进一步表明,支架产生复杂的细胞环境,促进细胞附着和随后的骨分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c18/7047255/f4388d32805f/biores.2020.0005_figure1.jpg

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