scholarly journals Retinal Organ Cultures as Alternative Research Models

2019 ◽  
Vol 47 (1) ◽  
pp. 19-29 ◽  
Author(s):  
Sven Schnichels ◽  
Tobias Kiebler ◽  
José Hurst ◽  
Ana M. Maliha ◽  
Marina Löscher ◽  
...  
Keyword(s):  
Animal Models ◽  
Organ Culture ◽  
Ex Vivo ◽  
Organ Cultures ◽  
Culture Systems ◽  
Cellular Processes ◽  
Experimental Systems ◽  
Vessel Morphology

Ex vivo organ cultures represent unique research models, as they combine the advantages of cell cultures with those of animal models. Being able to mimic in vivo situations through the use of organ cultures provides an excellent opportunity to investigate cellular processes, molecular pathways and cell–cell interactions, as well as structural and synaptic organisation. Human and animal organ cultures are now well established and comprise sensitive, easy-to-manipulate experimental systems that raise minimal ethical concerns. The eye, in particular, is a very complex organ that is not easy to reproduce in vitro. However, a lot of research has been dedicated to the development of suitable ocular organ cultures. This review covers the various ex vivo retinal organ culture systems available for use in ophthalmology research and compares them with commonly used animal models. In particular, bovine and porcine retinal organ culture systems are described, because the size, anatomy, physiology and vessel morphology of bovine and porcine eyes are similar to the human eye in an undisputed way, thus making them good models. In addition, these animals are widely used by the food industry and the eyes are considered surplus material. A short overview of murine, rat, rabbit, cat, canine and simian retinal organ cultures is also provided.

scholarly journals An Ex Vivo Vessel Injury Model to Study Remodeling

2018 ◽  
Vol 27 (9) ◽  
pp. 1375-1389 ◽  
Author(s):  
Mehmet H. Kural ◽  
Guohao Dai ◽  
Laura E. Niklason ◽  
Liqiong Gui
Keyword(s):  
Shear Stress ◽  
Animal Models ◽  
Intimal Hyperplasia ◽  
Vascular Remodeling ◽  
Ex Vivo ◽  
Vessel Injury ◽  
Injury Model ◽  
Human Arteries

Objective: Invasive coronary interventions can fail due to intimal hyperplasia and restenosis. Endothelial cell (EC) seeding to the vessel lumen, accelerating re-endothelialization, or local release of mTOR pathway inhibitors have helped reduce intimal hyperplasia after vessel injury. While animal models are powerful tools, they are complex and expensive, and not always reflective of human physiology. Therefore, we developed an in vitro 3D vascular model validating previous in vivo animal models and utilizing isolated human arteries to study vascular remodeling after injury. Approach: We utilized a bioreactor that enables the control of intramural pressure and shear stress in vessel conduits to investigate the vascular response in both rat and human arteries to intraluminal injury. Results: Culturing rat aorta segments in vitro, we show that vigorous removal of luminal ECs results in vessel injury, causing medial proliferation by Day-4 and neointima formation, with the observation of SCA1+ cells (stem cell antigen-1) in the intima by Day-7, in the absence of flow. Conversely, when endothelial-denuded rat aortae and human umbilical arteries were subjected to arterial shear stress, pre-seeding with human umbilical ECs decreased the number and proliferation of smooth muscle cell (SMC) significantly in the media of both rat and human vessels. Conclusion: Our bioreactor system provides a novel platform for correlating ex vivo findings with vascular outcomes in vivo. The present in vitro human arterial injury model can be helpful in the study of EC-SMC interactions and vascular remodeling, by allowing for the separation of mechanical, cellular, and soluble factors.

scholarly journals To Better Generate Organoids, What Can We Learn From Teratomas?

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongyu Li ◽  
Lixiong Gao ◽  
Jinlin Du ◽  
Tianju Ma ◽  
Zi Ye ◽  
...  
Keyword(s):  
Animal Models ◽  
Disease Modeling ◽  
3D Culture ◽  
Cellular Heterogeneity ◽  
Developmental Studies ◽  
Genomic Profile ◽  
Organization Studies ◽  
Culture Systems

The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.

scholarly journals In vitro and Animal Models for Antiviral Therapy in Papillomavirus Infections

1997 ◽  
Vol 8 (5) ◽  
pp. 381-400 ◽  
Author(s):  
MA Stanley ◽  
PJ Masterson ◽  
PK Nicholls
Keyword(s):  
Animal Models ◽  
Viral Gene Expression ◽  
Chemotherapeutic Agents ◽  
Viral Gene ◽  
Published Data ◽  
Papillomavirus Infections ◽  
Culture Systems ◽  
Species Specific

The need for antiviral therapies for papillomavirus infections is well recognized but the difficulties of reproducing the infectious cycle of papillomaviruses in vitro has hindered our understanding of virus-cell interactions and the regulation of viral gene expression during permissive growth. Recent advances in understanding the temporal expression and function of papillomavirus proteins has enabled consideration of a targeted approach to papillomavirus chemotherapy and in particular the inhibition of viral replication by targeting the E1 and E2 proteins. There are in vitro culture systems available for the screening of new chemotherapeutic agents, since significant advances have been made with culture systems which promote epithelial differentiation in vitro. However, to date, there are no published data which show that virions generated in vitro can infect keratinocytes and initiate another round of replication in vitro. In vivo animal models are therefore necessary to assess the efficacy of antivirals in preventing and treating viral infection, particularly for the low-risk genital viruses which are on the whole refractory to culture in vitro. Although papillomaviruses affect a wide variety of hosts in a species-specific manner, the animals most useful for modelling papillomavirus infections include the rabbit, ox, mouse, dog, horse, primate and sheep. The ideal animal model should be widely available, easy to house and handle, be large enough to allow for adequate tissue sampling, develop lesions on anatomical sites comparable with those in human diseases and these lesions should be readily accessible for monitoring and ideally should yield large amounts of infectious virus particles for use in both in vivo and in vitro studies. The relative merits of the various papillomavirus animal models available in relation to these criteria are discussed.

scholarly journals Atherosclerosis and Thrombosis: Insights from Large Animal Models

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Gemma Vilahur ◽  
Teresa Padro ◽  
Lina Badimon
Keyword(s):  
Animal Models ◽  
Ex Vivo ◽  
Large Animal ◽  
Isolated Cells ◽  
Large Animal Models ◽  
Thrombosis Research ◽  
Human Pathology ◽  
Thrombotic Complications

Atherosclerosis and its thrombotic complications are responsible for remarkably high numbers of deaths. The combination ofin vitro, ex vivo, andin vivoexperimental approaches has largely contributed to a better understanding of the mechanisms underlying the atherothrombotic process. Indeed, different animal models have been implemented in atherosclerosis and thrombosis research in order to provide new insights into the mechanisms that have already been outlined in isolated cells and protein studies. Yet, although no model completely mimics the human pathology, large animal models have demonstrated better suitability for translation to humans. Indeed, direct translation from mice to humans should be taken with caution because of the well-reported species-related differences. This paper provides an overview of the availableatherothrombotic-likeanimal models, with a particular focus on large animal models of thrombosis and atherosclerosis, and examines their applicability for translational research purposes as well as highlights species-related differences with humans.

scholarly journals Mastomys Species as Model Systems for Infectious Diseases

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 182 ◽  
Author(s):  
Daniel Hasche ◽  
Frank Rösl
Keyword(s):  
Animal Models ◽  
Laboratory Mouse ◽  
Model Systems ◽  
Experimental Systems ◽  
Non Melanoma Skin Cancer ◽  
In Vitro Systems ◽  
Mastomys Coucha ◽  
First Time

Replacements of animal models by advanced in vitro systems in biomedical research, despite exceptions, are currently still not satisfactory in reproducing the whole complexity of pathophysiological mechanisms that finally lead to disease. Therefore, preclinical models are additionally required to reflect analogous in vivo situations as found in humans. Despite proven limitations of both approaches, only a combined experimental arrangement guarantees generalizability of results and their transfer to the clinics. Although the laboratory mouse still stands as a paradigm for many scientific discoveries and breakthroughs, it is mandatory to broaden our view by also using nontraditional animal models. The present review will first reflect the value of experimental systems in life science and subsequently describes the preclinical rodent model Mastomys coucha that—although still not well known in the scientific community—has a long history in research of parasites, bacteria, papillomaviruses and cancer. Using Mastomys, we could recently show for the first time that cutaneous papillomaviruses—in conjunction with UV as an environmental risk factor—induce squamous cell carcinomas of the skin via a “hit-and-run” mechanism. Moreover, Mastomys coucha was also used as a proof-of-principle model for the successful vaccination against non-melanoma skin cancer even under immunosuppressive conditions.

scholarly journals Research Models for Studying Vascular Calcification

2020 ◽  
Vol 21 (6) ◽  
pp. 2204 ◽  
Author(s):  
Jaqueline Herrmann ◽  
Milen Babic ◽  
Markus Tölle ◽  
Markus van der Giet ◽  
Mirjam Schuchardt
Keyword(s):  
Animal Models ◽  
Vascular Calcification ◽  
Ex Vivo ◽  
Systemic Disease ◽  
Treatment Options ◽  
Aortic Tissue ◽  
Cardiovascular Morbidity And Mortality ◽  
Culture Models

Calcification of the vessel wall contributes to high cardiovascular morbidity and mortality. Vascular calcification (VC) is a systemic disease with multifaceted contributing and inhibiting factors in an actively regulated process. The exact underlying mechanisms are not fully elucidated and reliable treatment options are lacking. Due to the complex pathophysiology, various research models exist evaluating different aspects of VC. This review aims to give an overview of the cell and animal models used so far to study the molecular processes of VC. Here, in vitro cell culture models of different origins, ex vivo settings using aortic tissue and various in vivo disease-induced animal models are summarized. They reflect different aspects and depict the (patho)physiologic mechanisms within the VC process.

Computer Controlled Device to Independently Control Flow Waveform Parameters During Organ Culture and Biomechanical Testing of Mouse Carotid Arteries

2010 ◽  
Author(s):  
Seth Gazes ◽  
Alexander Caulk ◽  
Rudolph L. Gleason
Keyword(s):  
Organ Culture ◽  
Biomechanical Testing ◽  
The United States ◽  
Control Flow ◽  
In Vivo Models ◽  
Culture Systems ◽  
Novel Device ◽  
Vessel Growth

Understanding the mechanisms of cardiovascular disease progression is essential in developing novel therapies to combat this disease that contributes to 1 in 3 deaths in the United States every year. Endothelial dysfunction and its effects on vessel growth and remodeling are key factors in the progression and localization of atherosclerosis. Much of our understanding in this area has come from in-vivo and in-vitro experiments. However, perfused organ culture systems provide an alternative approach[1]. Organ culture systems can provide a more controlled mechanical, neural, and hormonal environment compared to in-vivo models. This study focused on furthering development of an organ culture model for mouse arteries by introducing a novel device to produce flow waveforms at the high frequencies and low mean flows seen in the mouse model.

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