Overexpressing sonic hedgehog peptide restores periosteal bone formation in a murine bone allograft transplantation model.
Overexpressing sonic hedgehog peptide restores periosteal bone formation in a murine bone allograft transplantation model.
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DOI：
10.1038/mt.2013.222
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发表时间：
2014-02
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影响因子：
--
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尽管hedgehog（Hh）信号的激活已被证明在体外诱导成骨分化和在体内诱导骨形成，但是Hh激活的间充质祖细胞在骨缺损修复中的潜在机制和潜在用途仍然是难以捉摸的。在这项研究中，我们证明了骨膜来源的间充质祖细胞（PDMPC），通过腺病毒载体（Ad-ShhN）过表达的N-末端音刺猬肽（ShhN）的植入恢复骨膜骨关节形成在4毫米节段性骨同种异体移植模型在免疫缺陷小鼠。术后2周，Ad-ShhN增强了供体细胞的存活和胶原支架中的微血管形成，并在术后6周诱导了供体细胞依赖性骨形成。活化细胞分选分析进一步显示，在手术后第7天，Ad-ShhN-PDMPC接种的支架含有比Ad-LacZ-PDMPC接种的支架多两倍的CD 45 −Sca-1+ CD 34 + VEGFR 2+内皮祖细胞。在内皮祖细胞和PDMPC的共培养中，Ad-ShhN转导的PDMPC诱导的CD 31+微血管形成是Ad-LacZ转导的PDMPC的1.8倍。总而言之，我们的数据表明，间充质祖细胞中ShhN的过表达通过增强供体祖细胞的存活、分化和受损骨膜部位的支架血运重建来改善骨缺损重建。因此，基于Hh激动剂的治疗值得进一步研究，以组织工程为基础的应用，旨在加强骨缺损的修复和重建。
Although activation of hedgehog (Hh) signaling has been shown to induce osteogenic differentiation in vitro and bone formation in vivo, the underlying mechanisms and the potential use of Hh-activated mesenchymal progenitors in bone defect repair remain elusive. In this study, we demonstrated that implantation of periosteal-derived mesenchymal progenitor cells (PDMPCs) that overexpressed an N-terminal sonic hedgehog peptide (ShhN) via an adenoviral vector (Ad-ShhN) restored periosteal bone collar formation in a 4-mm segmental bone allograft model in immunodeficient mice. Ad-ShhN enhanced donor cell survival and microvessel formation in collagen scaffold at 2 weeks after surgery and induced donor cell–dependent bone formation at 6 weeks after surgery. Fluorescence-activated cell sorting analysis further showed that Ad-ShhN-PDMPC–seeded scaffold contained a twofold more CD45−Sca-1+CD34+VEGFR2+ endothelial progenitors than Ad-LacZ-PDMPC–seeded scaffold at day 7 after surgery. Ad-ShhN–transduced PDMPCs induced a 1.8-fold more CD31+ microvessel formation than Ad-LacZ–transduced PDMPCs in a coculture of endothelial progenitors and PDMPCs. Taken together, our data show that overexpression of ShhN in mesenchymal progenitors improves bone defect reconstruction by enhancing donor progenitor cell survival, differentiation, and scaffold revascularization at the site of compromised periosteum. Hh agonist–based therapy, therefore, merits further investigation in tissue engineering–based applications aimed at enhancing bone defect repair and reconstruction.
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DOI：
10.1387/ijdb.103213sp
发表时间：
2011
期刊：
The International journal of developmental biology
影响因子：
--
作者：
Patel-Hett S;D'Amore PA
通讯作者：
D'Amore PA
影响因子：
37.8
作者：
Asai, Jun;Takenaka, Hideya;Losordo, Douglas W.
通讯作者：
Losordo, Douglas W.
影响因子：
2.8
作者：
Li, Ru;Stewart, Duncan J.;Schemitsch, Emil H.
通讯作者：
Schemitsch, Emil H.
影响因子：
8.2
作者：
Fu, Jin-Rong;Liu, Wen-Li;Zhou, Yu-Feng
通讯作者：
Zhou, Yu-Feng
影响因子：
4.1
作者：
Dohle, Eva;Fuchs, Sabine;Kirkpatrick, Charles James
通讯作者：
Kirkpatrick, Charles James