Title：Microbioreactor Array Screening of Wnt Modulators and Microenvironmental Factors in Osteogenic Differentiation of Mesenchymal Progenitor Cells

标题：微反应器阵列筛选Wnt调节剂和成骨分化中微环境因素的骨髓间充质祖细胞

Authors: Frith JE, Titmarsh DM, Padmanabhan H, Cooper-White JJ

作者： Frith JE, Titmarsh DM, Padmanabhan H, Cooper-White JJ

Journal: PLoS One, 2013

期刊： PLoS One, 2013

DOI: 10.1371/journal.pone.0082931

Abstract: This study explores the role of Wnt signaling and various microenvironmental factors in the osteogenic differentiation of mesenchymal progenitor cells (MPCs) using a microbioreactor array (MBA) platform. The researchers screened a range of Wnt activators and inhibitors, including CHIR99021 (a canonical Wnt activator), IWR-1 (a canonical Wnt inhibitor), and IWP-4 (an inhibitor of both canonical and non-canonical Wnt pathways). They utilized the MBA platform to identify conditions that promote or inhibit osteogenesis, providing insights into Wnt signaling pathways and their effects on MPC differentiation.

摘要： 本研究使用微生物反应器阵列（MBA）平台探讨了Wnt信号传导和各种微环境因素在间充质祖细胞（MPCs）成骨分化中的作用。研究人员筛选了一系列Wnt激活剂和抑制剂，包括CHIR99021（经典Wnt激活剂）、IWR-1（经典Wnt抑制剂）和IWP-4（经典和非经典Wnt通路抑制剂）。他们利用MBA平台识别促进或抑制成骨的条件，为Wnt信号传导路径及其对MPC分化的影响提供了见解。

Key Findings:

1. Wnt Signaling: The study highlights the complexity of Wnt signaling in MSCs, where canonical Wnt signaling can both maintain undifferentiated states and promote differentiation depending on the context.
2. MPC Subset: By using a well-defined MPC subset, the study minimizes variability and enhances the clarity of results related to signaling mechanisms.
3. Small Molecules: The research tested the effects of three small molecules (CHIR99021, IWR-1, and IWP-4) on MPC osteogenesis, offering potential applications in regenerative medicine and large-scale bioprocessing.

主要发现：

1. Wnt信号传导： 研究突出了MSC中Wnt信号传导的复杂性，在不同情境下，经典Wnt信号传导既能维持未分化状态又能促进分化。
2. MPC子集： 通过使用定义明确的MPC子集，研究减少了变量，提高了与信号机制相关结果的清晰度。
3. 小分子： 研究测试了三种小分子（CHIR99021、IWR-1和IWP-4）对MPC成骨的影响，提供了在再生医学和大规模生物处理中的潜在应用。

Materials and Methods:

• Reagents: CHIR99021 and IWP-4; IWR-1 .
• MPC Isolation and Culture: STRO-1-positive MPCs were prepared by Lonza and used under ethical approval from the University of Queensland.

材料和方法：

• 试剂： CHIR99021和IWP-4t；IWR-1。
• MPC分离与培养： STRO-1阳性MPCs由Lonza制备，并在昆士兰大学伦理批准下使用。

Compounds and CAS Numbers（化合物和CAS号）:

• CHIR99021: CAS 252917-06-9
• IWR-1: CAS 1127442-82-3
• IWP-4: CAS 686772-17-8