Dura mater stimulates human adipose-derived stromal cells to undergo bone formation in mouse calvarial defects.
Dura mater stimulates human adipose-derived stromal cells to undergo bone formation in mouse calvarial defects.
复制标题
DOI：
10.1002/stem.670
复制
发表时间：
2011-08
期刊：
影响因子：
5.2
通讯作者：
Longaker, Michael T.
中科院分区：
文献类型：
--
作者：
Levi, Benjamin;Nelson, Emily R.;Li, Shuli;James, Aaron W.;Hyun, Jeong S.;Montoro, Daniel T.;Lee, Min;Glotzbach, Jason P.;Commons, George W.;Longaker, Michael T.
关键词：
人类脂肪来源的基质细胞(HASCs)已被证实具有帮助颅骨缺损的骨修复的能力。然而，骨愈合所必需的骨缺损微环境尚不完全清楚。在本研究中，我们推测移植的ASCs和宿主硬脑膜(DM)细胞之间的细胞-细胞相互作用对颅骨缺损的修复至关重要。将hASCs植入临界大小的小鼠颅骨缺损区。DM-HASC的相互作用是通过手术切除DM或在DM和hASCs之间插入半透膜或非透膜来操纵的。进行了放射学、组织学和基因表达分析。其次，通过条件培养液(CM)和共培养实验来评估HASC-DM的相互作用。最后，利用新型骨形态发生蛋白-2和抗骨形态发生蛋白-2/4缓释支架，对糖尿病骨形态发生蛋白信号传导进行了体内研究。有了完整的DM，宿主DM和植入的hASCs都可以进行骨愈合。对DM-HASC相互作用的干扰显著减少了BMP-2-Smad-1/5信号通路的颅骨愈合。通过CM和共培养实验，小鼠DM细胞通过BMP信号通路刺激HASC成骨。通过对BMP-2途径的体内操作，我们发现BMP-2在DM刺激HASC成骨过程中在颅骨愈合过程中发挥着重要作用。在糖尿病受损的缺损处补充BMP-2，可在未愈合的缺损处形成骨。DM是一种成骨细胞类型，在HASC植入的颅骨缺损中既参与并促进骨愈合。此外，DM来源的BMP-2旁分泌刺激似乎在HASC介导的修复中发挥关键作用。
Human adipose-derived stromal cells (hASCs) have a proven capacity to aid in osseous repair of calvarial defects. However, the bone defect microenvironment necessary for osseous healing is not fully understood. In this study, we postulated that the cell-cell interaction between engrafted ASCs and host dura mater (DM) cells is critical for the healing of calvarial defects. hASCs were engrafted into critical sized calvarial mouse defects. The DM-hASC interaction was manipulated surgically by DM removal or by insertion of a semipermeable or nonpermeable membrane between DM and hASCs. Radiographic, histologic, and gene expression analyses were performed. Next, the hASC-DM interaction is assessed by conditioned media (CM) and coculture assays. Finally, bone morphogenetic protein (BMP) signaling from DM was investigated in vivo using novel BMP-2 and anti-BMP-2/4 slow releasing scaffolds. With intact DM, osseous healing occurs both from host DM and engrafted hASCs. Interference with the DM-hASC interaction dramatically reduced calvarial healing with abrogated BMP-2–Smad-1/5 signaling. Using CM and coculture assays, mouse DM cells stimulated hASC osteogenesis via BMP signaling. Through in vivo manipulation of the BMP-2 pathway, we found that BMP-2 plays an important role in DM stimulation of hASC osteogenesis in the context of calvarial bone healing. BMP-2 supplementation to a defect with disrupted DM allowed for bone formation in a nonhealing defect. DM is an osteogenic cell type that both participates in and stimulates osseous healing in a hASC-engrafted calvarial defect. Furthermore, DM-derived BMP-2 paracrine stimulation appears to play a key role for hASC mediated repair.
登录
查看更多内容
影响因子：
4.9
作者：
Aronin, Caren E. Petrie;Sadik, Karim W.;Lay, Ann L.;Rion, Dave B.;Tholpady, Sunil S.;Ogle, Roy C.;Botchwey, Edward A.
通讯作者：
Botchwey, Edward A.
影响因子：
3.6
作者：
Bradley, JP;Han, VKM;Longaker, MT
通讯作者：
Longaker, MT
影响因子：
3.6
作者：
Greenwald, JA;Mehrara, BJ;Longaker, MT
通讯作者：
Longaker, MT
影响因子：
2.6
作者：
Ferguson, C;Alpern, E;Helms, JA
通讯作者：
Helms, JA
影响因子：
3.6
作者：
Gosain, AK;Santoro, TD;Madoub, HS
通讯作者：
Madoub, HS