An Ex Vivo Vessel Injury Model to Study Remodeling.
An Ex Vivo Vessel Injury Model to Study Remodeling.
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DOI：
10.1177/0963689718792201
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发表时间：
2018-09
影响因子：
3.3
通讯作者：
Gui L
中科院分区：
文献类型：
--
作者：
Kural MH;Dai G;Niklason LE;Gui L
有创冠状动脉介入治疗可因内膜增生和再狭窄而失败。内皮细胞（EC）播散到血管腔，加速再内皮化，或局部释放mTOR通路抑制剂有助于减少血管损伤后的内膜增生。虽然动物模型是一种强大的工具，但它们既复杂又昂贵，而且并不总是能反映人类生理学。因此，我们开发了一个体外3D血管模型，验证了之前的体内动物模型，并利用分离的人类动脉来研究损伤后的血管重塑。方法：我们利用生物反应器来控制血管导管内的压力和剪切应力，研究大鼠和人类动脉对腔内损伤的血管反应。在体外培养大鼠主动脉段时，我们发现强力去除腔内内皮细胞会导致血管损伤，在第4天导致内侧增生和新内膜形成，并在第7天观察到在没有血流的情况下内膜中的SCA1+细胞（干细胞抗原-1）。相反，当剥去内皮的大鼠主动脉和人脐动脉受到动脉剪切应力时，预先播种人脐内皮细胞可显著降低大鼠和人血管介质中平滑肌细胞（SMC）的数量和增殖。我们的生物反应器系统提供了一个新的平台，将体外研究结果与体内血管结果相关联。目前的体外人动脉损伤模型可以通过分离机械、细胞和可溶性因素，有助于研究EC-SMC相互作用和血管重塑。
Invasive coronary interventions can fail due to intimal hyperplasia and restenosis. Endothelial cell (EC) seeding to the vessel lumen, accelerating re-endothelialization, or local release of mTOR pathway inhibitors have helped reduce intimal hyperplasia after vessel injury. While animal models are powerful tools, they are complex and expensive, and not always reflective of human physiology. Therefore, we developed an in vitro 3D vascular model validating previous in vivo animal models and utilizing isolated human arteries to study vascular remodeling after injury. Approach: We utilized a bioreactor that enables the control of intramural pressure and shear stress in vessel conduits to investigate the vascular response in both rat and human arteries to intraluminal injury. Culturing rat aorta segments in vitro, we show that vigorous removal of luminal ECs results in vessel injury, causing medial proliferation by Day-4 and neointima formation, with the observation of SCA1+ cells (stem cell antigen-1) in the intima by Day-7, in the absence of flow. Conversely, when endothelial-denuded rat aortae and human umbilical arteries were subjected to arterial shear stress, pre-seeding with human umbilical ECs decreased the number and proliferation of smooth muscle cell (SMC) significantly in the media of both rat and human vessels. Our bioreactor system provides a novel platform for correlating ex vivo findings with vascular outcomes in vivo. The present in vitro human arterial injury model can be helpful in the study of EC-SMC interactions and vascular remodeling, by allowing for the separation of mechanical, cellular, and soluble factors.
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影响因子：
10.8
作者：
Cheng, Wen-Pin;Wang, Bao-Wei;Shyu, Kou-Gi
通讯作者：
Shyu, Kou-Gi
影响因子：
37.8
作者：
Griese, DP;Ehsan, A;Dzau, VJ
通讯作者：
Dzau, VJ
影响因子：
37.8
作者：
Lau, George T.;Ridley, Lloyd J.;Kritharides, Leonard
通讯作者：
Kritharides, Leonard
影响因子：
37.8
作者：
Kong, D;Melo, LG;Dzau, VJ
通讯作者：
Dzau, VJ
影响因子：
23.9
作者：
Kramann, Rafael;Goettsch, Claudia;Wongboonsin, Janewit;Iwata, Hiroshi;Schneider, Rebekka K.;Kuppe, Christoph;Kaesler, Nadine;Chang-Panesso, Monica;Machado, Flavia G.;Gratwohl, Susannah;Madhurima, Kaushal;Hutcheson, Joshua D.;Jain, Sanjay;Aikawa, Elena;Humphreys, Benjamin D.
通讯作者：
Humphreys, Benjamin D.