scholarly journals Transgenic Rabbit Models: Now and the Future

2020 ◽  
Vol 10 (21) ◽  
pp. 7416
Author(s):  
Fumikazu Matsuhisa ◽  
Shuji Kitajima ◽  
Kazutoshi Nishijima ◽  
Toshiaki Akiyoshi ◽  
Masatoshi Morimoto ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Genetically Modified ◽  
Embryonic Stem ◽  
Experimental Manipulation ◽  
Biomedical Science ◽  
Current Status ◽  
Laboratory Animals ◽  
Transgenic Rabbit ◽  
Research Fields ◽  
Transgenic Rabbits

Transgenic rabbits have contributed to the progress of biomedical science as human disease models because of their unique features, such as the lipid metabolism system similar to humans and medium body size that facilitates handling and experimental manipulation. In fact, many useful transgenic rabbits have been generated and used in research fields such as lipid metabolism and atherosclerosis, cardiac failure, immunology, and oncogenesis. However, there have been long-term problems, namely that the transgenic efficiency when using pronuclear microinjection is low compared with transgenic mice and production of knockout rabbits is impossible owing to the lack of embryonic stem cells for gene targeting in rabbits. Despite these limitations, the emergence of novel genome editing technology has changed the production of genetically modified animals including the rabbit. We are finally able to produce both transgenic and knockout rabbit models to analyze gain- and loss-of-functions of specific genes. It is expected that the use of genetically modified rabbits will extend to various research fields. In this review, we describe the unique features of rabbits as laboratory animals, the current status of their development and use, and future perspectives of transgenic rabbit models for human diseases.

scholarly journals Genetically Modified Rabbits for Cardiovascular Research

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianglin Fan ◽  
Yanli Wang ◽  
Y. Eugene Chen
Keyword(s):  
Molecular Mechanisms ◽  
Genetically Modified ◽  
Embryonic Stem ◽  
Cardiovascular Research ◽  
Knock Out ◽  
Experimental Animals ◽  
Transgenic Rabbits ◽  
Long Time ◽  
Human Atherosclerosis ◽  
Genome Information

Rabbits are one of the most used experimental animals for investigating the mechanisms of human cardiovascular disease and lipid metabolism because they are phylogenetically closer to human than rodents (mice and rats). Cholesterol-fed wild-type rabbits were first used to study human atherosclerosis more than 100 years ago and are still playing an important role in cardiovascular research. Furthermore, transgenic rabbits generated by pronuclear microinjection provided another means to investigate many gene functions associated with human disease. Because of the lack of both rabbit embryonic stem cells and the genome information, for a long time, it has been a dream for scientists to obtain knockout rabbits generated by homologous recombination-based genomic manipulation as in mice. This obstacle has greatly hampered using genetically modified rabbits to disclose the molecular mechanisms of many human diseases. The advent of genome editing technologies has dramatically extended the applications of experimental animals including rabbits. In this review, we will update genetically modified rabbits, including transgenic, knock-out, and knock-in rabbits during the past decades regarding their use in cardiovascular research and point out the perspectives in future.

scholarly journals EXPERIMENTAL MODELS OF THE ATHEROSCLEROSIS ON RABBITS

2021 ◽  
Vol 28 (4) ◽  
pp. 78-87
Author(s):  
Aleksey M. Chaulin ◽  
Yulia V. Grigorieva ◽  
Galina N. Suvorova ◽  
Dmitry V. Duplyakov
Keyword(s):  
Lipid Metabolism ◽  
Plasma Cholesterol ◽  
Cholesterol Content ◽  
Genetic Mutation ◽  
Atherogenic Diet ◽  
Experimental Models ◽  
Normal Diet ◽  
Laboratory Animals ◽  
Therapeutic Effects ◽  
Transgenic Rabbits

Atherosclerosis is the main cause of cardiovascular diseases, which, despite a number of new advances in their diagnosis and treatment, still occupy a leading position. Experimental modeling of atherosclerosis in laboratory animals plays an important role in the study of the fundamental pathophysiological processes and pathology of atherosclerosis. Rabbits are among the most suitable animals for simulating atherosclerosis, as they are widely available, inexpensive to maintain, and easy to manipulate. The key advantage of rabbits over other animals is that their lipid metabolism is practically similar to that of humans. The aim of the study was to analyze literature data on experimental models of atherosclerosis in rabbits. The review shows that the history of the study of atherosclerosis by means of experimental models is very rich and originates from the works of the well-known Russian pathologists A.I. Ignatovsky, N.N. Anichkov, S.S. Khalatov (1908-1915), who developed a cholesterol model of the formation of atherosclerosis in rabbits. The principle of this model is to feed laboratory animals with food containing elevated levels of lipids and cholesterol. The composition of the cholesterol (atherogenic) diet may vary, determining the existence of modifications of this model. Most often, a diet with a cholesterol content of 0.3-0.5% is used, in cases where it is necessary to accelerate the development of atherosclerosis, a short-term use of a diet with a 1% cholesterol content is allowed. In addition to cholesterol, it is recommended to use vegetable oils (soybean, coconut or corn) in the atherogenic diet as they improve the absorption of cholesterol in the intestine. In 1980, Japanese researcher Y. Watanabe deduced a new model of atherosclerosis formation - on hereditarily determined hyperlipidemic rabbits Watanabe (WHHL-rabbits). WHHL rabbits contain a genetic mutation in the gene encoding low-density lipoprotein receptors, which results in these animals having high plasma cholesterol levels with a normal diet. Thanks to modern genetic technologies, various genetic models of atherosclerosis in rabbits have also been created: transgenic and “knocked out” rabbits. The main method for obtaining transgenic rabbits is pronuclear microinjection, which allows the introduction of a transgene (additional DNA fragment) into their genome. To date, using this technology, it has been possible to introduce more than a dozen genes responsible for lipid metabolism. The principle of creating knocked out rabbits consists in specific inactivation using genome editing technologies (ZFN, TALEN, CRISPR / Cas9) of a certain working gene. Experimental models of atherosclerosis in rabbits have not lost their significance and continue to be used to study the fundamental morphological (pathological) and pathological mechanisms underlying atherosclerosis, to search for new diagnostic biomarkers and potential targets for therapeutic effects, as well as to conduct preclinical trials of newly developed drugs.

Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Current Status ◽  
Cord Injury

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.

scholarly journals Direct Neuronal Reprogramming of Common Marmoset Fibroblasts by ASCL1, microRNA-9/9*, and microRNA-124 Overexpression

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 6
Author(s):  
Akisa Nemoto ◽  
Reona Kobayashi ◽  
Sho Yoshimatsu ◽  
Yuta Sato ◽  
Takahiro Kondo ◽  
...  
Keyword(s):  
Late Onset ◽  
Common Marmoset ◽  
Cellular Level ◽  
Biomedical Science ◽  
Disease Models ◽  
Specific Gene ◽  
Bhlh Transcription Factor ◽  
Research Fields ◽  
Microrna 124

The common marmoset (Callithrix jacchus) has attracted considerable attention, especially in the biomedical science and neuroscience research fields, because of its potential to recapitulate the complex and multidimensional phenotypes of human diseases, and several neurodegenerative transgenic models have been reported. However, there remain several issues as (i) it takes years to generate late-onset disease models, and (ii) the onset age and severity of phenotypes can vary among individuals due to differences in genetic background. In the present study, we established an efficient and rapid direct neuronal induction method (induced neurons; iNs) from embryonic and adult marmoset fibroblasts to investigate cellular-level phenotypes in the marmoset brain in vitro. We overexpressed reprogramming effectors, i.e., microRNA-9/9*, microRNA-124, and Achaete-Scute family bHLH transcription factor 1, in fibroblasts with a small molecule cocktail that facilitates neuronal induction. The resultant iNs from embryonic and adult marmoset fibroblasts showed neuronal characteristics within two weeks, including neuron-specific gene expression and spontaneous neuronal activity. As directly reprogrammed neurons have been shown to model neurodegenerative disorders, the neuronal reprogramming of marmoset fibroblasts may offer new tools for investigating neurological phenotypes associated with disease progression in non-human primate neurological disease models.

The Ethics of Embrionic Stem Cells Research

2019 ◽  
pp. 244-263
Author(s):  
Alexandra Huidu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cells ◽  
Embryonic Stem Cell ◽  
Stem Cell Research ◽  
Embryonic Stem ◽  
Modern Medicine ◽  
Embryonic Stem Cell Research ◽  
Hematopoietic Stem ◽  
Research Fields

Embrionic stem cells research, as opposed to hematopoietic stem cells research, has always stirred up many controversies of ethical nature that have projected their effects in the specialized doctrine of the domain of medical bioethics and law. Some of these controversies have been transposed at the legislative level (both by international normative acts and by the national laws of the states) while others are not yet de object of consensus. All that is not transposed by law remains in the exclusive sphere of ethics, so the ethical discussion in embryonic stem cell research is not only relevant for today's modern medicine but also of the utmost importance for a category of specialists in various research fields.

Investigation of the Stem Cells Used in Modeling Human Placental Trophoblast

2021 ◽  
Author(s):  
Lulu Ji ◽  
Lin Wang
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Cell Types ◽  
Model Systems ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
Placental Development ◽  
Induced Pluripotent

Human placenta is vital for fetal development, and act as an interface between the fetus and the expecting mother. Abnormal placentati on underpins various pregnancy complications such as miscarriage, pre-eclampsia and intrauterine growth restriction. Despite the important role of placenta, the molecular mechanisms governing placental formation and trophoblast cell lineage specification is poorly understand. It is mostly due to the lack of appropriate model system. The great various in placental types across mammals make it limit for the use of laboratory animals in studying human placental development. However, over the past few years, alternative methods have been employed, including human embryonic stem cells, induced pluripotent stem cells, human trophoblast stem cell, and 3-dimensional organoids. Herein, we summarize the present knowledge about human development, differentiated cell types in the trophoblast epithelium and current human placental trophoblast model systems.

scholarly journals Human Pluripotent Stem Cell Culture: Current Status, Challenges, and Advancement

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Sushrut Dakhore ◽  
Bhavana Nayer ◽  
Kouichi Hasegawa
Keyword(s):  
Stem Cells ◽  
Cell Culture ◽  
Pluripotent Stem Cells ◽  
Large Scale ◽  
Embryonic Stem ◽  
Current Status ◽  
Specific Cell ◽  
Therapeutic Applications ◽  
Proliferative Ability

Over the past two decades, human embryonic stem cells (hESCs) have gained attention due to their pluripotent and proliferative ability which enables production of almost all cell types in the human body in vitro and makes them an excellent tool to study human embryogenesis and disease, as well as for drug discovery and cell transplantation therapies. Discovery of human-induced pluripotent stem cells (hiPSCs) further expanded therapeutic applications of human pluripotent stem cells (PSCs). hPSCs provide a stable and unlimited original cell source for producing suitable cells and tissues for downstream applications. Therefore, engineering the environment in which these cells are grown, for stable and quality-controlled hPSC maintenance and production, is one of the key factors governing the success of these applications. hPSCs are maintained in a particular niche using specific cell culture components. Ideally, the culture should be free of xenobiotic components to render hPSCs suitable for therapeutic applications. Substantial efforts have been put to identify effective components, and develop culture conditions and protocols, for their large-scale expansion without compromising on quality. In this review, we discuss different media, their components and functions, including specific requirements to maintain the pluripotent and proliferative ability of hPSCs. Understanding the role of culture components would enable the development of appropriate conditions to promote large-scale, quality-controlled expansion of hPSCs thereby increasing their potential applications.

The Use of Genetically Modified Embryonic Stem Cells to Generate Transgenic Mice

2004 ◽  
Vol 40 (3) ◽  
pp. 235-238 ◽  
Author(s):  
M. V. Pryzhkova ◽  
I. R. Zakeeva ◽  
A. V. Kibardin ◽  
G. P. Georgiev ◽  
S. L. Kiselev
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Transgenic Mice ◽  
Genetically Modified ◽  
Embryonic Stem
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