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器官芯片-未来的迷你器官?

【 2019-2-14 发布 】 美迪医讯

到目前为止,体外方法和动物实验已被用于确定疾病的原因,研究治疗方法和预测药物的作用。现在,器官芯片模型提供了更准确和符合道德标准的替代方案。美迪医讯将带您了解有关模型,它们的优势和未来发展的更多信息。
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     体外过程和动物试验用于开发新的药物和新的治疗方法。然而,动物试验引起了重要的伦理问题。器官芯片模型有望成为一种可行的替代方案。在智能手机大小的系统中,器官通过人工循环连接。

器官芯片可用于研究药物的影响,以及疾病和治疗方法的原因。它们不仅具有成本效益,而且在动物实验和体外方法方面也是道德上合理的替代品。

在治疗和药物批准用于治疗和用于患者之前,仍然需要进行动物试验。这些测试旨在预测药物的活性和毒性及其对人体器官的影响。它们还使研究人员能够确定疾病的原因并开发新的治疗方法。医疗行业通过提供确保人类健康的经济有效的选择,从动物实验中受益。然而,尽管动物实验为医疗行业提供了优势,但它不仅符合大多数人的最佳利益,而且也符合研究公司的最佳利益,即取代动物试验或尽可能减少这些试验。但这怎么可能成为可行的选择?

智能手机大小的人体组织到目前进展如何?

作为动物实验的替代方案,科学家依靠培养器皿培养细胞。细胞嵌入二维环境中,甚至远不能与器官的自然生理环境相比。这使得几乎不可能准确地预测药物的效果。医学进展 - 其中包括干细胞研究 - 使得器官芯片系统成为可能。这些三维细胞和组织模型能够连续实时体外监测细胞群。器官芯片模型的关键优势在于它们以微观尺度复制特定器官和组织中人体细胞中发现的自然环境。到目前为止,“2-Organ-Chip”模型(2-OC)和“4-Organ-Chip”模型(4-OC)已经在医疗市场上取得了成功。前者根据两个器官和疾病的原因监测药物疗效和有效性和疾病,而后者研究四种类器官。然而,两种模型仅允许研究两个或四个器官的细胞,并且不能排除对其他类型细胞的不利影响。

来自3D打印机的器官芯片

3D打印技术使得“器官芯片”模型或芯片的制造成为可能。科学家们还必须拥有他们可以研究的器官细胞。这些细胞来自组织,该组织是来自手术或捐赠的医疗废物。然后将作为器官的最小功能单元的细胞分层施加到芯片上。细胞或类器官在该三维支架上生长并使用人工循环连接。循环由芯片的微通道组成,其由营养液灌注。泵模拟心脏的功能和节律,并通过芯片的通道传输营养液。后者的运作方式与人体血管相似。

当研究人员想要监测药物和毒素对器官的影响时,他们会将相应的物质注入组织并研究其影响。为此,必须彻底解剖器官碎片,以便监测细胞功能。剑桥大学的研究人员现已开发出一种将电极附着在细胞上的器官芯片模型。它们不是由金属制成,而是由导电聚合物海绵制成。这允许细胞通过电信号彼此通信,确保连续实时监测微型器官模型。与其他器官芯片系统不同,剑桥模型有助于长期实验。


微型器官的利弊

三维器官芯片模型是医学技术的重大进步,代表了二维细胞培养后的下一代。3D技术和基于细胞的分析使得不仅可以更仔细地检查人体器官和组织的生理学 - 例如它们受到药物和病原体的影响 - 而且还可以让研究人员清楚地了解治疗的类型。应该被接受或避免。另一个优点是,根据所涉及的器官,您可以将两个或更多器官组织结合起来,对靶器官进行有效的研究。同时,缺点是4-OC模型还不能正常工作,因为模拟血流非常困难。尽管由于细胞功能的实时监测,器官芯片加速了新药的开发,但目前这还不是技术上成熟的过程。海德堡大学医学院生理学和病理生理学研究所所长Thomas Korff教授警告说,“这里的危险就是概括事物。当我在一个结合肺部的器官芯片系统中测试一种物质时,肝脏,肾脏和肠道细胞,我没有发现任何不良反应,我只能得出结论,它在这个特定的系统和这些细胞中没有任何有害影响。错误的结论是推断不会对其他细胞产生副作用细胞类型。“ 话虽如此,要记住的一个重要方面是器官芯片解决了动物实验的伦理问题。虽然它们仍然无法完全取代动物测试,但它们至少可以显着降低它。更重要的是,这些系统大大推进了个性化医疗。

芯片患者的未来?

人体芯片或器官芯片是一种患者特异性芯片,实际上是人体的替代品和复制品。该芯片结合了所有人的器官,允许研究人员检查药物是否有帮助以及它如何影响特定患者。“我们的假设是,未来'芯片患者'可以为大多数疾病模式生成有意义的数据,并随后取代相应的动物实验,”柏林工业大学“多器官芯片”项目负责人Uwe Marx说。和TissUse GmbH的创始人。

另一个挑战是肝脏和脑细胞不能被培养。肝细胞在短短几天内死亡,使得长期实验几乎不可能。脑细胞每天繁殖需要一天才能通过称为突触的新结点传递信息。这就是为什么不可能准确描述中央功能,如全身血压和心脏和基底神经节功能,从而使持续的动物测试成为必要。话虽如此,研究的目的是避免将动物用于未来的医学实验,并将人类芯片系统作为替代方案。


Organ-on-a-chip Organs in miniature format

In vitro processes and animal tests are used to develop new medications and novel therapeutic approaches. However, animal testing raises important ethical concerns. Organ-on-a-chip models promise to be a feasible alternative. In a system the size of a smartphone, organs are connected using artificial circulation.

The human organism in smartphone size and what has happened so far

As an alternative to animal experiments, scientist have relied on the Petri dish to grow or culture cells. The cells are embedded in a two-dimensional environment, which is not even remotely comparable to the natural physiological environment of organs. This makes it nearly impossible to accurately predict the effects of medication. Advances in medicine – among them stem cell research – have made organ-on-a-chip systems possible. These three-dimensional cell and tissue models enable continuous real-time in vitro monitoring of cell populations. The key advantage of organ-on-a-chip models is that they replicate the natural environment found in human cells in specific organs and tissues at microscale. So far, the "2-Organ-Chip" model (2-OC) and the "4-Organ-Chip" model (4-OC) have proven successful in the medical market. The former monitors drug efficacy and effectiveness and diseases based on two organs and the causes of diseases, while the latter studies four organoids. However, both models only allow studies of the cells of either two or four organs and are unable to rule out adverse effects on other types of cells.


Organs on chips from the 3D printer


3D printing technology makes the fabrication of the "organ-on-a-chip" models or chips possible. Scientists must also have the cells of the organs they aim to research at their disposal. These cells are obtained from tissue that was either medical waste from surgeries or a donation. The cells, which are the smallest functional unit of the organs, are then applied in layers onto the chip. The cells or organoids are grown on this three-dimensional scaffold and connected using artificial circulation. The circulation is made up of microchannels of the chip, which are perfused by a nutrient solution. A pump simulates the heart’s function and rhythm and transports the nutrient solution through the channels of the chip. The latter operate like human blood vessels. Cells can grow in three dimensions on the organ-on-a-chip the same way they do inside the human body.


When researchers want to monitor the effects of drugs and toxins on organs, they inject the respective substance into the tissue and study its impact. To do this, organ chips must be completely dissected, so that the cell function can be monitored. Researchers at the University of Cambridge have now developed an organ-on-a-chip model that attaches electrodes to cells. These are not made from metal but of conductive polymer sponge. This allows the cells to communicate with each other by electrical signals, ensuring continuous real-time monitoring of the miniature organ models. Unlike other organ-on-a-chip systems, the Cambridge model facilitates longer-term experiments.


Pros and cons of miniature organs


The three-dimensional organ-on-a-chip models are a substantial advancement in medical technology and represent the next generation following two-dimensional cell culture. 3D technology and cell-based assays make it possible to not only more closely examine the physiology of human organs and tissues -  as they are affected by pharmaceutical substances and pathogens for instance – but to also give researchers a clear indication of the types of therapies that should be either embraced or avoided. Another advantage is that, depending on the organs in question, you can combine two or more organ tissues to conduct effective research on the target organs. Meanwhile, the drawback is that the 4-OC models don’t function properly yet because it is very difficult to mimic blood flow. Even though organ chips speed up the development of new drugs thanks to real-time monitoring of cell function, this is not a technically mature process at this point. Professor Thomas Korff, Director of the Institute of Physiology and Pathophysiology at the Medical Faculty of the Heidelberg University cautions that "the danger here is to generalize things. When I test a substance in an organ-on-a-chip system that combines lung, liver, kidney and intestinal cells, and I do not detect any adverse effects, I can only conclude that it has no harmful effects in this particular system and these cells. A false conclusion would be to infer that there would be no side effects on other types of cells." Having said that, one important aspect to remember is that organ chips address the ethical issues of animal experimentation. And although they are still not able to completely replace animal testing, they can at least significantly reduce it. What’s more, these systems considerably advance personalized medicine.


Chip patient of the future?


The human-on-a-chip or body-on-a-chip is a challenge in organ chip development. This is a patient-specific chip that is virtually a stand-in and duplicate of the human body. The chip combines all of a person’s organs, allowing researchers to check whether a medication helps and how it affects the particular patient. "Our assumption is that future ’chip patients’ can generate meaningful data for the majority of disease patterns and subsequently replace the respective animal experiments," says Uwe Marx, Head of the  "Multi-Organ-Chip" program at the Technical University of Berlin and founder of TissUse GmbH.


Another challenge is that liver and brain cells cannot be cultivated. Liver cells die within a few short days, rendering long-term experiments nearly impossible. Brain cells, which reproduce every day take up to a day before they pass information via new junctions called synapses. That’s why it is impossible to accurately depict central functions such as systemic blood pressure and cardiac and basal ganglia function, thus making continued animal testing necessary. Having said that, research aims to spare animals from being used in medical experiments in the future and apply human-on-a-chip systems as an alternative.

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