Functional characterization of 3D contractile smooth muscle tissues generated using a unique microfluidic 3D bioprinting technology
Functional characterization of 3D contractile smooth muscle tissues generated using a unique microfluidic 3D bioprinting technology
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DOI：
10.1096/fj.201901063rr
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发表时间：
2020-01-01
期刊：
影响因子：
4.8
通讯作者：
Wadsworth, Sam J.
中科院分区：
文献类型：
--
作者：
Dickman, Christopher T. D.;Russo, Valerio;Wadsworth, Sam J.
哮喘和炎症性肠病等疾病的特征是平滑肌收缩异常。由于实验室塑料的非生理化学和机械特性不允许肌肉细胞收缩，因此很难在2D体外培养物中开发模拟急性肌肉收缩的基于人类细胞的模型。为了增强体外模型与人类疾病的相关性，我们描述了如何使用独特的微流体3D生物打印技术可重复地制造具有生理和神经相关急性收缩和舒张反应的功能性3D平滑肌组织。将原代人气道和肠平滑肌细胞以高密度和活力打印成肌肉组织环。打印的组织收缩到生理浓度的组胺（0.01-100 μ M），并放松到沙丁胺醇，一种用于缓解哮喘恶化的药理学化合物。将TGF β添加到气道肌肉环诱导了未受刺激的肌肉缩短的增加和对沙丁胺醇的反应降低，这一现象也发生在慢性肺部疾病中。结果表明，3D生物打印平滑肌是一种生理相关的体外模型，可用于研究疾病途径以及新型治疗方法对急性收缩和慢性组织狭窄的影响。
Conditions such as asthma and inflammatory bowel disease are characterized by aberrant smooth muscle contraction. It has proven difficult to develop human cell-based models that mimic acute muscle contraction in 2D in vitro cultures due to the nonphysiological chemical and mechanical properties of lab plastics that do not allow for muscle cell contraction. To enhance the relevance of in vitro models for human disease, we describe how functional 3D smooth muscle tissue that exhibits physiological and pharmacologically relevant acute contraction and relaxation responses can be reproducibly fabricated using a unique microfluidic 3D bioprinting technology. Primary human airway and intestinal smooth muscle cells were printed into rings of muscle tissue at high density and viability. Printed tissues contracted to physiological concentrations of histamine (0.01-100 mu M) and relaxed to salbutamol, a pharmacological compound used to relieve asthmatic exacerbations. The addition of TGF beta to airway muscle rings induced an increase in unstimulated muscle shortening and a decreased response to salbutamol, a phenomenon which also occurs in chronic lung diseases. Results indicate that the 3D bioprinted smooth muscle is a physiologically relevant in vitro model that can be utilized to study disease pathways and the effects of novel therapeutics on acute contraction and chronic tissue stenosis.