Models of Respiratory Infections: Virus-Induced Asthma Exacerbations and Beyond

Sara Saturni,Marco Contoli,Antonio Spanevello,Alberto Papi 대한천식알레르기학회 2015 Allergy, Asthma & Immunology Research Vol.7 No.6

Respiratory infections are one of the main health problems worldwide. They are a challenging field of study due to an intricate relationship between the pathogenicity of microbes and the host’s defenses. To better understand mechanisms of respiratory infections, different models have been developed. A model is the reproduction of a disease in a system that mimics human pathophysiology. For this reason, the best models should closely resemble real-life conditions. Thus, the human model is the best. However, human models of respiratory infections have some disadvantages that limit their role. Therefore, other models, including animal, in vitro, and mathematical ones, have been developed. We will discuss advantages and limitations of available models and focus on models of viral infections as triggers of asthma exacerbations, viral infections being one of the most frequent causes of exacerbating disease. Future studies should focus on the interrelation of various models.

<i>In vitro</i> 3D skin model using gelatin methacrylate hydrogel

Kwak, Bong Shin,Choi, Wonho,Jeon, Joong-won,Won, Jong-In,Sung, Gun Yong,Kim, Bumsang,Sung, Jong Hwan Elsevier 2018 Journal of industrial and engineering chemistry Vol.66 No.-

<P><B>Abstract</B></P> <P>Interests in <I>in vitro</I> skin models have been growing. Collagen, which is a main scaffold material for in vitro 3D skin models, has weak mechanical properties, often resulting in undesirable contraction. The physiological characteristics of the skin models often depend on the matrix in which cells are cultured. In this study, we developed a 3D skin model using gelatin methacrylate. The mechanical and transport properties were studied, and attachment and growth of fibroblasts and keratinocytes were examined. Fibroblasts preferred softer matrix, whereas HaCaT cells preferred harder matrix of gelatin methacrylate. This study provides information for developing <I>in vitro</I> skin models.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

In vitro 3D skin model using gelatin methacrylate hydrogel

곽봉신,최원호,전중원,원종인,성건용,김범상,성종환 한국공업화학회 2018 Journal of Industrial and Engineering Chemistry Vol.66 No.-

Interests in in vitro skin models have been growing. Collagen, which is a main scaffold material for in vitro 3D skin models, has weak mechanical properties, often resulting in undesirable contraction. The physiological characteristics of the skin models often depend on the matrix in which cells are cultured. In this study, we developed a 3D skin model using gelatin methacrylate. The mechanical and transport properties were studied, and attachment and growth of fibroblasts and keratinocytes were examined. Fibroblasts preferred softer matrix, whereas HaCaT cells preferred harder matrix of gelatin methacrylate. This study provides information for developing in vitro skin models.

A comparison of liquid-liquid and air-liquid interface cultures of A549 cells for in vitro respiratory toxicity test

Ji-Hyun Bang,Hyun-Ok Ku,Byung-Suk Jeon,Nam-Ju Kim,Moon Her,Hee Yi 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

The adenocarcinomic human alveolar basal epithelial cells (A549) are commonly used for in vitro cell models of respiratory toxicity. In this study, we intended to establish in vitro culture models for respiratory toxicity testing by comparing air-liquid interface (ALI) conditions of A549 cells with liquid-liquid interface (LLI). A549 cells were seeded at 1*10^5 cells/well in an apical compartment of 12 well insert (Greiner Bio-one). Culture medium was added to the basolateral compartment and was replaced every 2-3 days in contact with cells for nutrient supply via the membrane. The medium was added only to the basolateral compartment in ALI culture condition while it was added to both apical and basolateral part in LLI culture method. During the culturing periods, A549 cells in ALI condition formed into multilayered epithelium with time, while the cells grown in LLI conditions formed into simple squamous epithelium over time. Because A549 cell is composed of basal epithelial cells, ciliated epithelial cells was not identified in this study during the 4 weeks of culturing period. Instead, epithelial specific morphology was well identified by hematoxylin and eosin staining after 4 weeks of culturing. Since cell culture interfaces and culture period affect cell formation, culture conditions need to be further optimized for in vitro respiratory toxicity test models.

In vitro and in vivo studies on theophylline mucoadhesive drug delivery system

Bandyopadhyay, AK,Perumal, P Kyung Hee Oriental Medicine Research Center 2007 Oriental pharmacy and experimental medicine Vol.7 No.1

Mucus is an aqueous gel complex with a constitution of about 95% water, high molecular weight glycoprotein (mucin), lipid, salts etc. Mucus appears to represent a significant barrier to the absorption of some compounds. Natural mucoadhesive agent was isolated and purified from the aqueous extract of the seeds of prosopis pallida (PP). Formulated tablet with the isolated material by wet granulation method. Some natural edible substances are in consideration for candidates as mucoadhesive agents to claim more effective controlled drug delivery as an alternative to the currently used synthetic mucoadhesive polymers. Subjected the materials obtained from natural source i.e. PP and standard synthetic substance, sodium carboxymethyl cellulose for evaluation of mucoadhesive property by various in vitro and in vivo methods. Through standard dissolution test and a model developed with rabbit, evaluated in vitro controlled release and bioadhesive property of theophylline formulation. Mucoadhesive agent obtained from PP showed good mucoadhesive potential in the demonstrated in vitro and in viνo models. The results suggest that the mucoadhesive agent showed controlled release properties by their application, substantially. In order to assess the gastrointestinal transit time in vivo, a radio opaque X-ray study performed in healthy rabbit testing the same controlled release formulation with and without bioadhesive polymer. Plasma levels of theophylline determined by the HPLC method and those allowed correlations to the in vitro mucoadhesive study results. Better correlation found between the results in different models. PP may acts as a better natural mucoadhesive agent in the extended drug delivery system.

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

Su-Jin Lee,Hyang-Ae Lee 대한생리학회-대한약리학회 2020 The Korean Journal of Physiology & Pharmacology Vol.24 No.6

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.

Retrospective growth kinetics and radiosensitivity analysis of various human xenograft models

이지영,김미숙,김은호,정남현,정윤경 한국실험동물학회 2016 Laboratory Animal Research Vol.32 No.4

The purpose of this study was to delineate the various factors that affect the growth characteristics of human cancer xenografts in nude mice and to reveal the relationship between the growth characteristics and radiosensitivity. We retrospectively analyzed 390 xenografts comprising nine different human cancer lines grown in nude mice used in our institute between 2009 and 2015. Tumor growth rate (TGR) was calculated using exponential growth equations. The relationship between the TGR of xenografts and the proliferation of the cells in vitro was examined. Additionally, we examined the correlations between the surviving fractions of cells after 2 Gy irradiation in vitro and the response of the xenograft to radiation. The TGR of xenografts was positively related to the proliferation of the cells in vitro ( r P =0.9714, p< 0.0001), whereas it was independent of the histological type of the xenografts. Radiation-induced suppression of the growth rate (T/C%) of xenografts was positively related to the radiosensitivity of the cells in vitro (SF 2 ; r P =0.8684, p=0.0284) and TGR (r P =0.7623, p=0.0780). The proliferation of human cancer cells in vitro and the growth rate of xenografts were positively related. The radiosensitivity of cancer cells, as judged from the SF 2 values in vitro, and the radiation-induced suppression of xenograft growth were positively related. In conclusion, the growth rate of human xenografts was independent of histological type and origin of the cancer cells, and was positively related to the proliferation of the cancer cells in vitro.

Gaining New Biological and Therapeutic Applications into the Liver with 3D In Vitro Liver Models

Lee Sang Woo,Jung Da Jung,Jeong Gi Seok 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.6

Background: Three-dimensional (3D) cell cultures with architectural and biomechanical properties similar to those of natural tissue have been the focus for generating liver tissue. Microarchitectural organization is believed to be crucial to hepatic function, and 3D cell culture technologies have enabled the construction of tissue-like microenvironments, thereby leading to remarkable progress in vitro models of human tissue and organs. Recently, to recapitulate the 3D architecture of tissues, spheroids and organoids have become widely accepted as new practical tools for 3D organ modeling. Moreover, the combination of bioengineering approach offers the promise to more accurately model the tissue microenvironment of human organs. Indeed, the employment of sophisticated bioengineered liver models show long-term viability and functional enhancements in biochemical parameters and disease-orient outcome. Results: Various 3D in vitro liver models have been proposed as a new generation of liver medicine. Likewise, new biomedical engineering approaches and platforms are available to more accurately replicate the in vivo 3D microarchitectures and functions of living organs. This review aims to highlight the recent 3D in vitro liver model systems, including micropatterning, spheroids, and organoids that are either scaffold-based or scaffold-free systems. Finally, we discuss a number of challenges that will need to be addressed moving forward in the field of liver tissue engineering for biomedical applications. Conclusion: The ongoing development of biomedical engineering holds great promise for generating a 3D biomimetic liver model that recapitulates the physiological and pathological properties of the liver and has biomedical applications.

Ex Vivo Live Full-thickness Porcine Skin Model for Skin Barrier Research

( Kyung-min Lim ) 한국피부장벽학회 2021 한국피부장벽학회지 Vol.23 No.2

Traditionally, skin barrier research has been done using experimental animals but animal tests are gradually phasing out due to concern on animal welfare and species difference to predict human physiology. To replace animal tests for skin barrier research, various in vitro human skin models have been developed such as reconstructed human epidermis models, ex vivo skin models. However, these models have their own pros and cons, such as high costs, donor to donor variation, leaky stratum corneum or incomplete epidermal differentiation, that need to be addressed by a new in vitro skin model. In this context, ex vivo live porcine skin model can be a useful alternative to replace animal tests for skin barrier research as well as for diverse topics regarding cosmetics. Here, the advantages of ex vivo live porcine skin model for skin barrier research are discussed.

Novel extended <i>in vitro-in vivo</i> correlation model for the development of extended-release formulations for baclofen: From formulation composition to <i>in vivo</i> pharmacokinetics

Kim, Tae Hwan,Bulitta, Jü,rgen B.,Kim, Do-Hyung,Shin, Soyoung,Shin, Beom Soo Elsevier 2019 International journal of pharmaceutics Vol.556 No.-

<P><B>Abstract</B></P> <P> <I>In vitro-in vivo</I> correlation (IVIVC), a predictive mathematical model between the <I>in vitro</I> dissolution and the <I>in vivo</I> pharmacokinetics has been utilized for the development of new extended release (ER) formulations. The aim of the present study was to extend the IVIVC approach, which correlates among the formulation composition, the <I>in vitro</I> dissolution, and the plasma drug concentration, to predict plasma drug concentrations from a given composition of the formulation, and vice versa, using baclofen as a model drug. Baclofen ER tablets with different dissolution rates were prepared by varying the composition of hydroxypropyl methylcellulose (HPMC). First, the HPMC compositions and the corresponding <I>in vitro</I> dissolutions parameters were correlated, and then the <I>in vitro</I> dissolution parameters were correlated with the <I>in vivo</I> dissolution parameters extracted from the pharmacokinetic profiles of the baclofen ER formulations <I>via</I> population pharmacokinetic modeling. The final extended IVIVC model linked the composition of the formulation, the <I>in vitro</I> dissolution, and the <I>in vivo</I> plasma concentration profile and was successfully applied for the prediction of <I>in vivo</I> pharmacokinetics from the amount of HPMC in baclofen ER formulations. The present approach holds great promise for designing optimal compositions of ER formulations to present desired plasma concentration profile.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>