纽约大学开发出能够模拟人体肾脏功能的新设备

2017-02-10 10:31:36 来源: 中国科技网 作者: 张微编译

不是在活体肾脏上运行测试,而是纽约州立大学的研究人员开发了一个模型肾脏,用于解决肾脏疾病在药物和治疗上的缺陷。

由助理教授格雷琴 马勒和她在宾汉姆顿生物医学工程的校友Courtney Sakolish博士开发的这个可重复使用的、多层微流体装置,将多孔生长基质与生理体液和位于肾脏末端的起过滤作用的毛细血管(称为肾小球,为血液过滤器)集成在一起。

“这是用来研究药物与细胞或组织(特别是肾脏)之间相互作用的特殊平台,目前该领域研究还是空白” Sakolish说。“在临床测试之前,这些平台有望在将来进行动物替代实验,以便更加准确地指导该领域研究,能够成功地在人类身上应用。”

“这是组织工程,但不是为了替换一个人的器官或组织,”马勒说。“我们的想法是,以简单的方式重建主要器官的功能,作用药物筛选工具。寻找新药物非常困难,而且价格昂贵,效率也不高。我们希望在生理环境下通过测试人类细胞,可以引导资源投向最有希望的备选药物,并更快地确定其他不合格的备选新药物。”

结果表明,比起传统的培养方法,在我们的装置中,细胞生长展示出了更加自然的行为,通过肾小球过滤对健康细胞功能来说是必要的。

“我们发现,更加复杂、动态的培养条件(就如本项目中所用的)对于准确预测肾脏药物毒性非常必要,” Sakolish说。“当我们用传统静态培养和我们的新模型,对比肾脏功能和药物毒性的时候,我们发表细胞表现的显著差异。相比于传统的静态培养,在我们的平台上,细胞看起来以及表现起来都和在人体中是一样的,显示出对药物更加敏感的反应。”

马勒说,虽然其他人已经开发了近端肾小管微流体模型,但我们的研究首次提供了肾小球过滤的模型。

“这种类型的装置在一个动态,更接近人体生理环境的情况下利用细胞,比起动物实验(动物研究往往不适用于人类)或静态的细胞培养(这是最常用的临床前筛选工具),它能更好地预测身体对药物的反应,”马勒说。

研究论文,“模拟人体近端肾小管和肾小球的创新微流体装置,”已经发表在RSC Advances期刊上。(张微编译)

以下为英文原文:

Researchers develop device that emulates human kidney function

Instead of running tests on live kidneys, researchers at Binghamton, University State University of New York have developed a model kidney for working out the kinks in medicines and treatments.

Developed by Assistant Professor Gretchen Mahler and Binghamton biomedical engineering alumna Courtney Sakolish PhD '16, the reusable, multi-layered and microfluidic device incorporates a porous growth substrate, with a physiological fluid flow, and the passive filtration of the capillaries around the end of a kidney, called the glomerulus, where waste is filtered from blood.

"This is a unique platform to study interactions between drugs andcells or tissues, specifically in the kidney, where current models were lacking," said Sakolish. "These platforms will, hopefully, in the future, be used as an animal alternative during pre-clinical testing to more accurately direct these studies toward successful results in humans."'

"This is tissue engineering, but not for the purpose or replacing an organ or tissue in a person," said Mahler. "The idea is that we can recreate the major organ functions in a simplified way for use as a drug screening tool. Finding new drugs is very hard, expensive and inefficient. We hope that by using human cells in a physiological environment we can help to direct resources toward the most promising new drug candidates and determine that other new drug candidates will fail, faster."

Results suggest that cells grown in the device exhibit more natural behaviors than when grown in traditional culturing methods, and the filtration by the glomerulus is necessary for healthy cell function.

"We found that the more complex, dynamic culturing conditions (like those used in this project) are necessary to accurately predict renal drug toxicity in human systems," said Sakolish. "When we compared physiological renal function and drug toxicity in traditional static culturing against our new model, we found significant differences in the ways that cells behaved. In our platform, cells looked and acted like those that you would find in the body, showing more sensitive responses to drugs than traditional static culturing."

Mahler said that while others have developed microfluidic models of the proximal tubule before, this is the first to offer glomerular filtration.

"This type of device uses human cells in a dynamic, more physiologic environment, potentially making it better at predicting the body's response to drugs than animals (animal effectiveness studies often don't translate to humans) or static cell cultures, which are the most commonly used preclinical screening tools," said Mahler.

The paper, "A novel microfluidic device to model the human proximal tubule and glomerulus," was published in RSC Advances.

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