FTY720 Promotes Local Microvascular Network Formation and Regeneration of Cranial Bone Defects
FTY720 Promotes Local Microvascular Network Formation and Regeneration of Cranial Bone Defects
复制标题
DOI：
10.1089/ten.tea.2009.0539
复制
发表时间：
2010-06-01
影响因子：
4.1
通讯作者：
Botchwey, Edward A.
中科院分区：
文献类型：
--
作者：
Aronin, Caren E. Petrie;Sefcik, Lauren S.;Botchwey, Edward A.
颅骨微环境包含一个独特的祖细胞生态位，在设计再生策略时，应该考虑进行治疗操作。最近，我们的团队证明了从硬脑膜分离的细胞是多能的，并在体外表现出扩张潜力和对可生物降解结构的强大矿化作用。在这项研究中，我们评估了通过促进微血管网络的生长和通过靶向鞘氨醇1-磷酸(S1P)受体的药物将宿主硬脑膜前体运输到缺损区来修复临界大小的颅骨缺损的有效性。我们证明，向(S1P)受体S1P(1)和S1P(3)输送药物激动剂显著增加骨生长、总微血管密度，以及在缺损区内新生微血管上的平滑肌细胞投资。此外，体外增殖和迁移研究表明，选择性激活S1P(3)可以促进成骨前体细胞从脑膜中招募和生长。
The calvarial bone microenvironment contains a unique progenitor niche that should be considered for therapeutic manipulation when designing regeneration strategies. Recently, our group demonstrated that cells isolated from the dura are multipotent and exhibit expansion potential and robust mineralization on biodegradable constructs in vitro. In this study, we evaluate the effectiveness of healing critical-sized cranial bone defects by enhancing microvascular network growth and host dura progenitor trafficking to the defect space pharmacologically by delivering drugs targeted to sphingosine 1-phosphate (S1P) receptors. We demonstrate that delivery of pharmacological agonists to (S1P) receptors S1P(1) and S1P(3) significantly increase bone ingrowth, total microvessel density, and smooth muscle cell investment on nascent microvessels within the defect space. Further, in vitro proliferation and migration studies suggest that selective activation of S1P(3) promotes recruitment and growth of osteoblastic progenitors from the meningeal dura mater.