A dynamic bioreactor for endothelial and epithelial cell co-culture to mimic aspects of renal microenvironments

IF 4.4 4区 医学 Q3 ENGINEERING, BIOMEDICAL
Todd P. Burton, Andrew P. Johnston, Anthony Callanan
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Abstract

There is a pressing need for alternative treatment approaches for chronic kidney disease (CKD), a condition which affects a significant proportion of the global population. In vitro tissue-engineered models offer a promising solution by developing a physiologically relevant representation of the kidney’s microenvironment. Key criteria in the development of such an environment include a three-dimensional cell culture material, consideration of the interactions of multiple cell types, and the provision of a fluidic environment. Herein, we investigate the use of a bioreactor platform which can maintain epithelial and endothelial cells, seeded on an either side of electrospun scaffolds, within a dynamic fluidic environment. Validation of the bioreactor’s capacity to maintain these cell types in co-culture and deliver a physiologically relevant shear stress was demonstrated via colorimetric testing and computational fluid dynamics respectively. Subsequent analysis of the viability, DNA content, morphology, protein and gene expression of both cell types indicate significant variations in cellular responses depending on their culture environments. The results of this work support the use of the bioreactor system as an effective means of replicating aspects of the renal tubule microenvironment, and thus may progress future treatments of CKD.

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内皮细胞和上皮细胞共同培养的动态生物反应器,模拟肾脏微环境的各个方面。
慢性肾脏疾病(CKD)是一种影响全球很大一部分人口的疾病,迫切需要替代治疗方法。体外组织工程模型通过开发肾脏微环境的生理学相关表示提供了一个有前途的解决方案。开发这种环境的关键标准包括三维细胞培养材料,考虑多种细胞类型的相互作用,以及提供流体环境。在此,我们研究了生物反应器平台的使用,该平台可以在动态流体环境中维持上皮细胞和内皮细胞,并将其植入电纺丝支架的两侧。分别通过比色测试和计算流体动力学验证了生物反应器在共培养中维持这些细胞类型并提供生理相关剪切应力的能力。随后对两种细胞的活力、DNA含量、形态、蛋白质和基因表达的分析表明,细胞反应的显著差异取决于它们的培养环境。这项工作的结果支持使用生物反应器系统作为复制肾小管微环境方面的有效手段,从而可能推动未来CKD的治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biomedical Microdevices
Biomedical Microdevices 工程技术-工程:生物医学
CiteScore
6.90
自引率
3.60%
发文量
32
审稿时长
6 months
期刊介绍: Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology is an interdisciplinary periodical devoted to all aspects of research in the medical diagnostic and therapeutic applications of Micro-Electro-Mechanical Systems (BioMEMS) and nanotechnology for medicine and biology. General subjects of interest include the design, characterization, testing, modeling and clinical validation of microfabricated systems, and their integration on-chip and in larger functional units. The specific interests of the Journal include systems for neural stimulation and recording, bioseparation technologies such as nanofilters and electrophoretic equipment, miniaturized analytic and DNA identification systems, biosensors, and micro/nanotechnologies for cell and tissue research, tissue engineering, cell transplantation, and the controlled release of drugs and biological molecules. Contributions reporting on fundamental and applied investigations of the material science, biochemistry, and physics of biomedical microdevices and nanotechnology are encouraged. A non-exhaustive list of fields of interest includes: nanoparticle synthesis, characterization, and validation of therapeutic or imaging efficacy in animal models; biocompatibility; biochemical modification of microfabricated devices, with reference to non-specific protein adsorption, and the active immobilization and patterning of proteins on micro/nanofabricated surfaces; the dynamics of fluids in micro-and-nano-fabricated channels; the electromechanical and structural response of micro/nanofabricated systems; the interactions of microdevices with cells and tissues, including biocompatibility and biodegradation studies; variations in the characteristics of the systems as a function of the micro/nanofabrication parameters.
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