eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering.
eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering.
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DOI：
10.1002/term.1645
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发表时间：
2015-11
影响因子：
3.3
通讯作者：
DiMuzio, Paul
中科院分区：
文献类型：
--
作者：
McIlhenny, Stephen;Zhang, Ping;Tulenko, Thomas;Comeau, Jason;Fernandez, Sarah;Policha, Aleksandra;Ferroni, Matthew;Faul, Elizabeth;Bagameri, Gabor;Shapiro, Irving;DiMuzio, Paul
关键词：
本研究评估了一种新型组织工程血管（TEBV）的耐久性，该血管是通过将分化为内皮样细胞的自体脂肪源性干细胞（ASC）植入天然血管组织支架（去细胞化的人大隐静脉异体移植物）而产生的。该模型先前的研究表明，移植物具有血栓形成性，可能是由于内皮分化不足，一氧化氮（NO）的产生很少。为了评估NO在种子细胞中表达的重要性，我们使用转染内皮型一氧化氮合酶（eNOS）基因的自体ASC构建TEBV以产生NO。我们发现转染的ASC在体外产生的NO水平与内皮细胞（EC）对照组相似，并且能够引起体外主动脉标本的血管松弛。用产生no的ASC制造的TEBV （n=5）作为插入移植物植入兔子的主动脉内，保持专利两个月，与未播种的对照组相比，显示出非血栓形成表面（n=5）。尽管支架具有异种移植物的性质，但TEBV结构在种子移植物中仍然保存完好。总之，本研究表明，在分化为内皮样细胞的成体干细胞中，一氧化氮表达的上调赋予了非血栓性表型，并强调了在血管组织工程应用中用作内皮细胞替代品的细胞产生一氧化氮的重要性。
This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels similar to endothelial cell (EC) controls in vitro and capable of causing vasorelaxation of aortic specimens ex vivo. TEBV (n=5) created with NO-producing ASC and implanted as interposition grafts within the aorta of rabbits remained patent for two months and demonstrated a non-thrombogenic surface compared to unseeded controls (n=5). Despite the xenograft nature of the scaffold, TEBV structure remained well-preserved in seeded grafts. In sum, this study demonstrates that up-regulation of NO expression within adult stem cells differentiated towards an endothelial-like cell imparts a non-thrombogenic phenotype and highlights the importance of NO production by cells to be used as endothelial cell substitutes in vascular tissue engineering applications.
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影响因子：
3.3
作者：
Hoetzer, Greta L.;Van Guilder, Gary P.;DeSouza, Christopher A.
通讯作者：
DeSouza, Christopher A.
影响因子：
4.1
作者：
McIlhenny, Stephen E.;Hager, Eric S.;DiMuzio, Paul J.
通讯作者：
DiMuzio, Paul J.
影响因子：
37.8
作者：
Miranville, A;Heeschen, C;Bouloumié, A
通讯作者：
Bouloumié, A
DOI：
10.1152/ajpheart.00685.2006
发表时间：
2007-03-01
影响因子：
4.8
作者：
Bivalacqua, Trinity J.;Deng, Weiwen;Kadowitz, Philip J.
通讯作者：
Kadowitz, Philip J.
影响因子：
1.1
作者：
DiMuzio, Paul;Fischer, Lauren;Tulenko, Thomas
通讯作者：
Tulenko, Thomas