• Title/Summary/Keyword: Organ-on-a-chip

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Blood-brain barrier-on-a-chip for brain disease modeling and drug testing

  • Cui, Baofang;Cho, Seung-Woo
    • BMB Reports
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    • v.55 no.5
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    • pp.213-219
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    • 2022
  • The blood-brain barrier (BBB) is an interface between cerebral blood and the brain parenchyma. As a gate keeper, BBB regulates passage of nutrients and exogeneous compounds. Owing to this highly selective barrier, many drugs targeting brain diseases are not likely to pass through the BBB. Thus, a large amount of time and cost have been paid for the development of BBB targeted therapeutics. However, many drugs validated in in vitro models and animal models have failed in clinical trials primarily due to the lack of an appropriate BBB model. Human BBB has a unique cellular architecture. Different physiologies between human and animal BBB hinder the prediction of drug responses. Therefore, a more physiologically relevant alternative BBB model needs to be developed. In this review, we summarize major features of human BBB and current BBB models and describe organ-on-chip models for BBB modeling and their applications in neurological complications.

Trends in MEA-based Neuropharmacological Drug Screening (MEA 기반 신경제약 스크리닝 기술 개발 동향)

  • Y.H. Kim;S.D. Jung
    • Electronics and Telecommunications Trends
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    • v.38 no.1
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    • pp.46-54
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    • 2023
  • The announcement of the US Environmental Protection Agency that it will stop conducting or funding experimental studies on mammals by 2035 should prioritize ongoing efforts to develop and use alternative toxicity screening methods to animal testing. Toxicity screening is likely to be further developed considering the combination of human-induced pluripotent-stem-cell-derived organ-on-a-chip and multielectrode array (MEA) technologies. We briefly review the current status of MEA technology and MEA-based neuropharmacological drug screening using various cellular model systems. Highlighting the coronavirus disease pandemic, we shortly comment on the importance of early prediction of toxicity by applying artificial intelligence to the development of rapid screening methods.

Trends in the development of human stem cell-based non-animal drug testing models

  • Lee, Su-Jin;Lee, Hyang-Ae
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.6
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    • pp.441-452
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    • 2020
  • In vivo animal models are limited in their ability to mimic the extremely complex systems of the human body, and there is increasing disquiet about the ethics of animal research. Many authorities in different geographical areas are considering implementing a ban on animal testing, including testing for cosmetics and pharmaceuticals. Therefore, there is a need for research into systems that can replicate the responses of laboratory animals and simulate environments similar to the human body in a laboratory. An in vitro two-dimensional cell culture model is widely used, because such a system is relatively inexpensive, easy to implement, and can gather considerable amounts of reference data. However, these models lack a real physiological extracellular environment. Recent advances in stem cell biology, tissue engineering, and microfabrication techniques have facilitated the development of various 3D cell culture models. These include multicellular spheroids, organoids, and organs-on-chips, each of which has its own advantages and limitations. Organoids are organ-specific cell clusters created by aggregating cells derived from pluripotent, adult, and cancer stem cells. Patient-derived organoids can be used as models of human disease in a culture dish. Biomimetic organ chips are models that replicate the physiological and mechanical functions of human organs. Many organoids and organ-on-a-chips have been developed for drug screening and testing, so competition for patents between countries is also intensifying. We analyzed the scientific and technological trends underlying these cutting-edge models, which are developed for use as non-animal models for testing safety and efficacy at the nonclinical stages of drug development.

Current and Future Perspectives of Lung Organoid and Lung-on-chip in Biomedical and Pharmaceutical Applications

  • Junhyoung Lee;Jimin Park;Sanghun Kim;Esther Han;Sungho Maeng;Jiyou Han
    • Journal of Life Science
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    • v.34 no.5
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    • pp.339-355
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    • 2024
  • The pulmonary system is a highly complex system that can only be understood by integrating its functional and structural aspects. Hence, in vivo animal models are generally used for pathological studies of pulmonary diseases and the evaluation of inhalation toxicity. However, to reduce the number of animals used in experimentation and with the consideration of animal welfare, alternative methods have been extensively developed. Notably, the Organization for Economic Co-operation and Development (OECD) and the United States Environmental Protection Agency (USEPA) have agreed to prohibit animal testing after 2030. Therefore, the latest advances in biotechnology are revolutionizing the approach to developing in vitro inhalation models. For example, lung organ-on-a-chip (OoC) and organoid models have been intensively studied alongside advancements in three-dimensional (3D) bioprinting and microfluidic systems. These modeling systems can more precisely imitate the complex biological environment compared to traditional in vivo animal experiments. This review paper addresses multiple aspects of the recent in vitro modeling systems of lung OoC and organoids. It includes discussions on the use of endothelial cells, epithelial cells, and fibroblasts composed of lung alveoli generated from pluripotent stem cells or cancer cells. Moreover, it covers lung air-liquid interface (ALI) systems, transwell membrane materials, and in silico models using artificial intelligence (AI) for the establishment and evaluation of in vitro pulmonary systems.

Sasang Constitutional Medicine in the Genomics Era (Genomics 시대의 사상체질의학)

  • Park Hwa-Yong;Yoon Yoo-Sik;Kim Jong-Yeol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.6
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    • pp.1475-1482
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    • 2005
  • It is over 100 years after Lee Je Ma has proposed concept of the Sasang constitutional medicine in his book DongEuiSooSeBoWon in 1894. As well known, this concept describes four constitution of Taeyang, Taeum, Soyang, and Soeum which are deals with physical body status and shape, desease and symptoms, personal characters, and organ function. In these days there are growing needs to elucidate this Sasang concept by the scientific manner, especially by biological tools. However there are no genes revealed related to the Sasang and moreover it is not easy to give a biological evidence for the Sasang constitution. Here are some considerations about the brief history of biological research on the Sasang constitution, and some prospectives of how to do to find genes of Sasang, and which to be done for what is about Sasang.

Establishing porcine jejunum-derived intestinal organoids to study the function of intestinal epithelium as an alternative for animal testing

  • Bo Ram Lee;Sun A Ock;Mi Ryung Park;Min Gook Lee;Sung June Byun
    • Journal of Animal Reproduction and Biotechnology
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    • v.39 no.1
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    • pp.2-11
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    • 2024
  • Background: The small intestine plays a crucial role in animals in maintaining homeostasis as well as a series of physiological events such as nutrient uptake and immune function to improve productivity. Research on intestinal organoids has recently garnered interest, aiming to study various functions of the intestinal epithelium as a potential alternative to an in vivo system. These technologies have created new possibilities and opportunities for substituting animals for testing with an in vitro model. Methods: Here, we report the establishment and characterisation of intestinal organoids derived from jejunum tissues of adult pigs. Intestinal crypts, including intestinal stem cells from the jejunum tissue of adult pigs (10 months old), were sequentially isolated and cultivated over several passages without losing their proliferation and differentiation using the scaffold-based and three-dimensional method, which indicated the recapitulating capacity. Results: Porcine jejunum-derived intestinal organoids showed the specific expression of several genes related to intestinal stem cells and the epithelium. Furthermore, they showed high permeability when exposed to FITC-dextran 4 kDa, representing a barrier function similar to that of in vivo tissues. Collectively, these results demonstrate the efficient cultivation and characteristics of porcine jejunum-derived intestinal organoids. Conclusions: In this study, using a 3D culture system, we successfully established porcine jejunum-derived intestinal organoids. They show potential for various applications, such as for nutrient absorption as an in vitro model of the intestinal epithelium fused with organ-on-a-chip technology to improve productivity in animal biotechnology in future studies.