Patient-Specific 3-Dimensional Model of Smooth Muscle Cell and Extracellular Matrix Dysfunction for the Study of Aortic Aneurysms

用于研究主动脉瘤的患者特异性平滑肌细胞和细胞外基质功能障碍的三维模型

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作者:Natalija Bogunovic, Jorn P Meekel, Jisca Majolée, Marije Hekhuis, Jakob Pyszkowski, Stefan Jockenhövel, Magnus Kruse, Elise Riesebos, Dimitra Micha, Jan D Blankensteijn, Peter L Hordijk, Samaneh Ghazanfari, Kak K Yeung

Conclusion

We present a valuable preclinical model of AAA constructed with patient specific cells with applications in both translational research and therapeutic developments. We observed SMC spatial reorganization in a time course of 5 weeks in our robust, patient-specific model of SMC-EC organization and ECM production.

Methods

SMC isolated from the medial layer of were the aortic wall of controls and AAA patients seeded on electrospun poly-lactide-co-glycolide scaffolds and cultured for 5 weeks, after which endothelial cells (EC) are added. Cell morphology, orientation, mechanical properties and ECM production were quantified for validation and comparison between controls and patients.

Results

We show that cultured SMC proliferate into multiple layers after 5 weeks in culture and produce ECM proteins, mimicking their behavior in the medial aortic layer. EC attach to multilayered SMC, mimicking layer interactions. The novel SMC model exhibits viscoelastic properties comparable to biological vessels; cytoskeletal organization increases during the 5 weeks in culture; increased cytoskeletal alignment and decreased ECM production indicate different organization of AAA patients' cells compared with control.

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