大鼠心脏成纤维细胞——恰好是心脏的形状——生长在模拟心脏组织的水凝胶上，用人类血清处理. (Photo: Brian Aguado)
CU Boulder engineers and faculty from the Consortium for Fibrosis Research & Translation 科罗拉多大学安舒茨医学院(CU Anschutz Medical Campus)的研究人员合作开发了基于生物材料的心脏组织“模拟物”，以测量患者对主动脉瓣置换术的反应, 为心脏组织术后重塑提供了新的视角.
Aortic valve stenosis (AVS), 一种进行性疾病，以心脏瓣膜组织硬化和心脏血流受阻为特征, is known as a “silent killer,” affecting 12.75岁以上人口的4%，如果不及时治疗，死亡范围为2-5年. Transcatheter aortic valve replacement (TAVR) procedures, which place an artificial valve at the site of the blockage, have been widely and successfully adopted as a remedy in recent decades.
对瓣膜置换术更广泛的生物反应的细节在很大程度上仍然未知, 但是对于量化经济复苏的质量有着重要的影响, the risk of complications and the assessment of overall patient outcomes.
During AVS disease progression, tissue-specific cells known as fibroblasts transition into myofibroblasts, which promote tissue stiffening. The researchers were interested in understanding how and why, post TAVR, myofibroblasts revert to the more benign fibroblasts.
“先前的研究表明，心脏组织在干预后发生了显著的重塑。. 该研究的主要作者，博彩平台推荐的博士后研究员布莱恩·阿瓜多说 Department of Chemical and Biological Engineering. “博彩平台推荐的假设是，也许患者血液中的生化线索可能使肌成纤维细胞恢复成纤维细胞.”
Modeling such a transformation in the lab is one thing, Aguado said, 但这项新研究的关键是从真正的AVS患者身上获取血液样本，然后使用生物材料来复制心脏的微环境.
“The heart is not made of plastic like a petri dish is,” he said. “博彩平台推荐需要设计出能够反映健康和患病瓣膜和心脏组织的各种刚度的材料.”
猪瓣膜成纤维细胞在模拟瓣膜组织的水凝胶上生长并经人血清处理. (Photo: Brian Aguado)
研究人员收集了AVS患者tavr术前和术后的血清样本，然后在定制的水凝胶环境中处理培养的心肌细胞, maintaining a near-facsimile of the in vivo cardiac conditions before and after TAVR.
The researchers were able to quantify protein expression in patient sera, 在主动脉和心脏组织在TAVR后重塑和重建过程中，鉴定与肌成纤维细胞失活相关的关键蛋白.
“博彩平台推荐的实验室专注于将水凝胶作为细胞外组织微环境的模拟物," said Dr. 克里斯蒂·安赛斯，化学与生物工程杰出教授 Precision Biomaterials IRT. “为这些研究开发的水凝胶系统使博彩平台推荐能够评估患者特异性生化线索, found in human sera, can impact cellular phenotypes. 博彩平台推荐的患者特异性观察将不可能使用传统的组织培养塑料材料."
“细胞外基质蛋白过度沉积导致的心脏纤维化是一个大问题,” said Timothy McKinsey, professor of medicine and director of the CFReT, 这是科罗拉多大学医学院转型研究基金倡议支持的项目之一. “除此之外，纤维化会导致心脏变得僵硬，损害其放松的能力. 博彩平台推荐对将博彩平台推荐目前的发现转化为心脏和血管纤维化疾病的创新疗法的潜力感到兴奋.”
这项研究也可能在未来对观察到的男性和女性在康复方面的差异有更深入的了解. 先前的临床研究表明，男性在tavr后似乎经历了更多的心脏组织重塑, 新的数据发现，男性心肌细胞的肌成纤维细胞逆转确实比女性细胞更为明显, 尽管需要进一步的研究来了解不同临床背景下的性别特异性差异.
“We were a bit surprised by the breadth of these findings,” Aguado said. “博彩平台推荐不认为瓣膜植入会对整个身体系统产生如此深远的影响. 博彩平台推荐的工程模型和临床数据之间的联系为这一结论提供了支持.”
Overall, Aguado said, 结果表明，TAVR过程确实会引发有益的蛋白质反应，生物材料模型和临床样本可以为确定未来的治疗机会提供有用的桥梁.
“We are getting better at engineering disease models, but we’re reaching a crossroads where models can only do so much,” he said. “未来将依赖于将患者样本与这些模型结合使用，以更好地了解患者的疾病进展. In collaboration with physicians, 博彩平台推荐可以看到实验室的进展如何转化为对患者更有效的治疗方法.”
The new study was published today in the journal Science Translational Medicine. Additional co-authors of the new study include Joseph Grim, Cierra Walker, Tova Ceccato, Anne Cox and Leslie Leinwand of CU Boulder; Katherine Schuetze and Carmen Sucharov of the CU Anschutz Medical Campus; Aik-Choon Tan of the Colorado School of Public Health; and Matthew Taylor of the University of Colorado Health Science Center. The National Institutes of Health (NIH), the National Science Foundation (NSF), the American Heart Association, the U.S. 美国教育部和巴勒斯惠康基金会为这项研究提供了资金.
