Abstract：
Morbidity and mortality rates associated with atherosclerosis-related diseases are increasing. Therefore, developing new research models is important in furthering our understanding of atherosclerosis and investigate novel treatments. Here, we designed novel vascular-like tubular tissues from multicellular spheroids composed of human aortic smooth muscle cells, endothelial cells, and fibroblasts using a bio-3D printer. We also evaluated their potential as a research model for Mönckeberg\'s medial calcific sclerosis. The tubular tissues were sufficiently strong to be handled 1 week after printing and could still be cultured for 3 weeks. Histological assessment showed that calcified areas appeared in the tubular tissues within 1 week after culture in a medium containing inorganic phosphate (Pi) or calcium chloride as the calcification-stimulating factors. Calcium deposition was confirmed using micro-computed tomography imaging. Real-time quantitative reverse transcription polymerase chain reaction analysis revealed that the expression of osteogenic transcription factors increased in calcified tubular tissues. Furthermore, the administration of Pi and rosuvastatin enhanced tissue calcification. The bio-3D printed vascular-like tubular structures, which are composed of human-derived cells, can serve as a novel research model for Mönckeberg\'s medial calcific sclerosis.
摘要：
与动脉粥样硬化相关疾病的发病率和死亡率正在增加。因此,开发新的研究模型对于加深我们对动脉粥样硬化的理解和研究新的治疗方法很重要.这里,我们从由人主动脉平滑肌细胞（SMC）组成的多细胞球体中设计了新的血管样管状组织，内皮细胞，和使用生物3D打印机的成纤维细胞。我们还评估了它们作为Mönckeberg内侧钙化硬化研究模型的潜力。管状组织足够坚固以在打印后1周进行处理,并且仍然可以培养3周。组织学评估显示，在含有无机磷酸盐（Pi）或氯化钙作为钙化刺激因子的培养基中培养后1周内，肾小管组织中出现钙化区域。使用显微计算机断层扫描成像确认钙沉积。实时定量逆转录PCR分析显示，钙化肾小管组织中成骨转录因子的表达增加。此外，Pi和瑞舒伐他汀的给药增强了组织钙化。生物3D打印的血管状管状结构，由人类来源的细胞组成，可以作为Mönckeberg内侧钙化硬化的新研究模型。
