Pyrvinium, a potent small molecule Wnt inhibitor, increases engraftment and inhibits lineage commitment of mesenchymal stem cells (MSCs).
Pyrvinium, a potent small molecule Wnt inhibitor, increases engraftment and inhibits lineage commitment of mesenchymal stem cells (MSCs).
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吡氏菌是一种有效的小分子Wnt抑制剂，可增加植入并抑制间充质干细胞（MSC）的谱系承诺。
DOI：
10.1111/j.1524-475x.2012.00767.x
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发表时间：
2012-03
期刊：
影响因子：
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通讯作者：
Young PP
中科院分区：
文献类型：
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作者：
Saraswati S;Deskins DL;Holt GE;Young PP
我们和其他人发现，Wnt信号抑制在间充质干细胞(MSC)自我更新过程中起着重要作用。在对小分子的化学筛选中，吡喃被认为是一种有效的Wnt抑制剂。在本研究中，我们假设吡喃将促进MSC的自我更新，以提高MSC的临床疗效。吡喃可促进体外培养的骨髓间充质干细胞的增殖，同时通过减少细胞质中的β-连环蛋白来抑制其成骨和成软骨的谱系承诺。尽管MSCs是一个很有希望的细胞治疗靶点，但提高其存活率和维持其在损伤区域的干细胞能力的策略是必不可少的。利用肉芽组织形成的体内模型，我们证明了吡喃促进了MSC的长期植入。吡喃处理的骨髓间充质干细胞生成的肉芽组织也显示出较少的异位分化为骨或软骨。这项研究强调了使用治疗性Wnt抑制剂来增强MSC驱动的再生治疗的潜力。
We and others have found that Wnt signaling inhibition is important in mesenchymal stem cell (MSC) self-renewal. Pyrvinium was identified as a potent Wnt inhibitor in a chemical screen for small molecules. In the present study we hypothesized that pyrvinium will enhance MSC self-renewal to improve the clinical efficacy of MSC therapy. Pyrvinium increased MSC proliferation in vitro while inhibiting their osteogenic and chondrogenic lineage commitment by reducing cytoplasmic β-catenin. Although MSCs are a promising target for cell therapy, strategies to enhance their survival and maintain their stemness in the wounded area are essential. Using an in vivo model of granulation tissue formation, we demonstrated that pyrvinium enhanced long-term MSC engraftment. Pyrvinium treated MSC-generated granulation tissue also demonstrated less ectopic differentiation into bone or cartilage. This study highlights the potential of using a therapeutic Wnt inhibitor to enhance MSC-driven regenerative therapy.