Livestock in biomedical research: history, current status and future prospective

2016 ◽  
Vol 28 (2) ◽  
pp. 112 ◽  
Author(s):  
Irina A. Polejaeva ◽  
Heloisa M. Rutigliano ◽  
Kevin D. Wells
Keyword(s):  
Genome Sequence ◽  
Biomedical Research ◽  
Assisted Reproductive Technologies ◽  
Sequence Data ◽  
Embryonic Stem ◽  
Reproductive Technologies ◽  
Farm Animals ◽  
Current Status ◽  
Large Animal ◽  
Large Animal Models

Livestock models have contributed significantly to biomedical and surgical advances. Their contribution is particularly prominent in the areas of physiology and assisted reproductive technologies, including understanding developmental processes and disorders, from ancient to modern times. Over the past 25 years, biomedical research that traditionally embraced a diverse species approach shifted to a small number of model species (e.g. mice and rats). The initial reasons for focusing the main efforts on the mouse were the availability of murine embryonic stem cells (ESCs) and genome sequence data. This powerful combination allowed for precise manipulation of the mouse genome (knockouts, knockins, transcriptional switches etc.) leading to ground-breaking discoveries on gene functions and regulation, and their role in health and disease. Despite the enormous contribution to biomedical research, mouse models have some major limitations. Their substantial differences compared with humans in body and organ size, lifespan and inbreeding result in pronounced metabolic, physiological and behavioural differences. Comparative studies of strategically chosen domestic species can complement mouse research and yield more rigorous findings. Because genome sequence and gene manipulation tools are now available for farm animals (cattle, pigs, sheep and goats), a larger number of livestock genetically engineered (GE) models will be accessible for biomedical research. This paper discusses the use of cattle, goats, sheep and pigs in biomedical research, provides an overview of transgenic technology in farm animals and highlights some of the beneficial characteristics of large animal models of human disease compared with the mouse. In addition, status and origin of current regulation of GE biomedical models is also reviewed.

Pluripotent cells in farm animals: state of the art and future perspectives

2013 ◽  
Vol 25 (1) ◽  
pp. 103 ◽  
Author(s):  
Monika Nowak-Imialek ◽  
Heiner Niemann
Keyword(s):  
Animal Models ◽  
Es Cells ◽  
Laboratory Mouse ◽  
Embryonic Stem ◽  
Farm Animals ◽  
Large Animal ◽  
Pluripotent Cells ◽  
Unique Type ◽  
Large Animal Models

Pluripotent cells, such as embryonic stem (ES) cells, embryonic germ cells and embryonic carcinoma cells are a unique type of cell because they remain undifferentiated indefinitely in in vitro culture, show self-renewal and possess the ability to differentiate into derivatives of the three germ layers. These capabilities make them a unique in vitro model for studying development, differentiation and for targeted modification of the genome. True pluripotent ESCs have only been described in the laboratory mouse and rat. However, rodent physiology and anatomy differ substantially from that of humans, detracting from the value of the rodent model for studies of human diseases and the development of cellular therapies in regenerative medicine. Recently, progress in the isolation of pluripotent cells in farm animals has been made and new technologies for reprogramming of somatic cells into a pluripotent state have been developed. Prior to clinical application of therapeutic cells differentiated from pluripotent stem cells in human patients, their survival and the absence of tumourigenic potential must be assessed in suitable preclinical large animal models. The establishment of pluripotent cell lines in farm animals may provide new opportunities for the production of transgenic animals, would facilitate development and validation of large animal models for evaluating ESC-based therapies and would thus contribute to the improvement of human and animal health. This review summarises the recent progress in the derivation of pluripotent and reprogrammed cells from farm animals. We refer to our recent review on this area, to which this article is complementary.

scholarly journals Large Animal Models of Glioma: Current Status and Future Prospects

2021 ◽  
Vol 41 (11) ◽  
pp. 5343-5353
Author(s):  
WILLIAM H. HICKS ◽  
CYLAINA E. BIRD ◽  
MARK N. PERNIK ◽  
ALI S. HAIDER ◽  
AKSHARKUMAR DOBARIYA ◽  
...  
Keyword(s):  
Animal Models ◽  
Current Status ◽  
Large Animal ◽  
Future Prospects ◽  
Large Animal Models

scholarly journals Current Status of Sex Sorted Semen and its Long Term effect on Population Dynamics and Y-Chromosome Degeneration of the Breed Among Dairy Animals in Jharkhand, India: A Review

2021 ◽  
pp. 34-44
Author(s):  
N. Kumari ◽  
S. Prasad ◽  
A. K. Pandey ◽  
S. Dash ◽  
R. Sinha
Keyword(s):  
Population Dynamics ◽  
Y Chromosome ◽  
Assisted Reproductive Technologies ◽  
Negative Impact ◽  
Research Work ◽  
Reproductive Technologies ◽  
Current Status ◽  
Effective Population ◽  
Female Population ◽  
Y Chromosome Degeneration

Sex Sorted Semen gives the liberty of producing offspring of the desired sex - in farming animals by using it in conjunction with other assisted reproductive technologies such as Artificial Insemination and In-Vitro Fertilization after selecting the healthy sperm and separating into X-Female and Y-male Chromosome bearing populations based on their DNA content. It is an important biotechnological tool to increase the milk production and the profitability of Dairy Industry. Current study deals with the Principle, methods, main method, advantages, disadvantages and the current status of Sex sorted semen in India and Jharkhand. The main emphasis of this study is to draw the attention of Scientific fraternity towards the effect of Sex Sorted Semen on Population dynamics. The Sex Sorted semen increases the deviation of ratio between Male and Female Population from ideal 1:1, thereby decreasing the effective population size Ne and thus slowly reducing the viability and survivability of the population or breed concerned. Further the already depleting Y chromosomes will be reaped off all its genes in long run at a faster rate due to antagonistic selection pressure arising out of Artificial selection via Sex Sorted Semen acting against all the gene of Y chromosome of the breed or population concerned which might disturb many vital genes and the associated functions. The degeneration and extinction of scientists have been predicted long ago. The effect of Sex Sorted semen on Y- chromosome degeneration is yet to be pointed out, calculated and subsequently verified in any of the literatures. SSS is indeed a boon for India as well as Jharkhand. It might be too early to predict about the negative impact of SSS on population dynamics and Y-Chromosome degeneration. Further research work must be done to assess the extent and authencity of above mentioned impact( Predicted  theoretically) by calculation as well as practical field based Experimentation.

scholarly journals Effective repair of joint cartilage using human pluripotent stem cell-derived tissue

2018 ◽  
Author(s):  
Oliver F. W. Gardner ◽  
Subhash C. Juneja ◽  
Heather Whetstone ◽  
Yulia Nartiss ◽  
Jakob T. Sieker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Articular Cartilage ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Type Ii Collagen ◽  
Cartilage Tissue ◽  
Large Animal ◽  
Large Animal Models ◽  
Joint Repair ◽  
Rat Tissue

Adult articular cartilage lacks significant regenerative capacity, and damage to this tissue often leads to progressive joint degeneration (osteoarthritis). We developed strategies to generate articular cartilage from human pluripotent stem cells (hPSCs) as a source of clinically relevant tissues for joint repair1. Previously, we demonstrated that these chondrocytes retain cartilage forming potential following subcutaneous implantation in mice. In this report, we evaluated the potential of human embryonic stem cell (hESC)-derived articular cartilage tissue to repair osteochondral defects created in the rat knee. Following implantation, the hESCderived cartilage maintained a proteoglycan and type II collagen-rich matrix, and was well integrated with native rat tissue at the basal and lateral surfaces. The ability to generate cartilage tissue with integrative and reparative properties from an unlimited and robust cell source represents a significant clinical advance for cartilage repair that can be applied to large animal models and ultimately to patient care.

scholarly journals Roles of steroid hormones in oviductal function

Reproduction ◽  
2020 ◽  
Vol 159 (3) ◽  
pp. R125-R137 ◽  
Author(s):  
Brooke E Barton ◽  
Gerardo G Herrera ◽  
Prashanth Anamthathmakula ◽  
Jenna K Rock ◽  
Anna M Willie ◽  
...  
Keyword(s):  
Steroid Hormones ◽  
Embryo Development ◽  
Muscle Cell ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Farm Animals ◽  
Cell Functions ◽  
Laboratory Rodents ◽  
Embryo Transport ◽  
And Function

The oviduct (known as the fallopian tube in humans) is the site for fertilization and pre-implantation embryo development. Female steroid hormones, estrogen and progesterone, are known to modulate the morphology and function of cells in the oviduct. In this review, we focus on the actions of estrogen and progesterone on secretory, ciliated, and muscle cell functions and morphologies during fertilization, pre-implantation embryo development, and embryo transport in humans, laboratory rodents and farm animals. We review some aspects of oviductal anatomy and histology and discuss current assisted reproductive technologies (ARTs) that bypass the oviduct and their effects on embryo quality. Lastly, we review the causes of alterations in secretory, ciliated, and muscle cell functions that could result in embryo transport defects.

276 CHARACTERIZATION OF BOVINE EPIBLAST OUTGROWTH COLONIES DERIVED FROM DAY 12 BLASTOCYSTS

2008 ◽  
Vol 20 (1) ◽  
pp. 218
Author(s):  
E. Østrup ◽  
K. Schauser ◽  
J. O. Gjørret ◽  
P. Maddox-Hyttel
Keyword(s):  
Es Cells ◽  
Cell Sheet ◽  
Calf Serum ◽  
Embryonic Stem ◽  
Large Animal ◽  
Santa Cruz ◽  
Cuboidal Cell ◽  
The Core ◽  
Large Animal Models

Isolation and culture of mouse embryonic stem (ES) cells has been performed for many years, and the improvements achieved throughout the last decade in the human field has evoked great hopes for future cell replacement therapies. However, despite certain similarities in the molecular regulation of pluripotency between man and mouse, there is a need for developing large animal models. The aim of our study was to isolate, culture, and characterize bovine ES-like cell colonies derived from the epiblast. Embryos were produced by in vitro maturation, fertilization, and culture. After 6 days of in vitro culture, blastocysts were transferred to synchronized heifers and allowed to develop for an additional 6 days in vivo. At Day 12 after insemination, embryos were collected by nonsurgical flushing. Embryonic discs were isolated from 15 blastocysts by microsurgery and cultured on mitomycin-inactivated mouse embryonic fibroblasts (SLN cells) in DMEM/F12 medium supplemented with 15% fetal calf serum (FCS), 5% knockout serum replacement (KSR), 106UmL–1 leukemia inhibitory factor (LIF), basic fibroblast growth factor (bFGF), nonessential amino acids (NEAA), and nucleosides. After 4 (n = 6), 6 (n = 4), and 8 days (n = 5) of culture, the primary outgrowth colonies were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned, and exposed to antisera recognizing Oct-4 (pluripotency marker; Santa Cruz Biotechnology, Santa Cruz, CA, USA), Vimentin (mesenchyme marker; Zymed Laboratories, South San Francisco, CA, USA), Cytokeratin-8 (trophectoderm marker; Becton, Dickinson and Co., Franklin Lakes, NJ, USA), and α-1-Fetoprotein (hypoblast marker; DakoCytomation, Glostrup, Denmark). The site of antigen-antibody reaction was revealed using the ABC-AEC-method and counterstained with hematoxylin. At Day 4, all colonies had developed a compact central core of cells with a low cytoplasm-to-nucleus ratio, surrounded by a monolayer of squamous cells. At Days 6 and 8, 3 out of 4 and 3 out of 5 colonies, respectively, still presented the compact core which occasionally was encapsulated by a squamous or cuboidal cell sheet. In the remaining colonies, a compact core was less defined. Oct-3/4 staining was observed in the nuclei of the compact core in 5 out of 6 colonies on Day 4, and in all colonies presenting a compact core on Days 6 and 8. However, whereas all nuclei in the core were stained on Days 4 and 6, only scattered nuclei were stained on Day 8. Vimentin staining was observed in the cytoplasm of cells in the compact core in 3 out of 6 Day 4 colonies, in all Day 6 colonies presenting a compact core, but not in any Day 8 colonies. In contrast, α-1-Fetoprotein staining intensity increased with culture period and was mostly observed in squamous monolayer portions. Cytokeratin-8 staining was weak and restricted to the cytoplasm of the cells encapsulating and surrounding the core in 2 Day 6 colonies and a single Day 8 colony. In conclusion, epiblasts isolated from Day 12 bovine blastocysts efficiently attach to feeder cells and develop outgrowth colonies with cores containing presumptive pluripotent cells (Oct-4). However, these cells to some degree lost Oct-4 expression toward Day 8 and were, in parallel, to some degree overgrown by cells of hypoblast (α-1-Fetoprotein) and trophectoderm (Cytokeratin-8) origin.

scholarly journals Genome sequence of a pathogenic Corynebacterium ulcerans strain isolated from a wild boar with necrotizing lymphadenitis

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Anne Busch ◽  
Jens Möller ◽  
Andreas Burkovski ◽  
Helmut Hotzel
Keyword(s):  
Wild Boar ◽  
Genome Sequence ◽  
Sequence Data ◽  
Farm Animals ◽  
Economic Losses ◽  
Corynebacterium Ulcerans ◽  
Skin Ulcers ◽  
Growth Properties ◽  
Necrotizing Lymphadenitis ◽  
Systemic Infections

Abstract Objectives Corynebacterium ulcerans can colonize a wide variety of animals and also humans are infected, typically by zoonotic transmission. Symptoms range from skin ulcers or systemic infections to diphtheria-like illness. In contrast, Corynebacterium pseudotuberculosis is widely distributed among herds of sheep, goats and other farm animals, where it causes high economic losses due to caseous lymphadenitis. Here we describe the genome sequence of an atypical C. ulcerans strain isolated from a wild boar with necrotizing lymphadenitis. This strain has similarities to C. pseudotuberculosis. Data description Genome sequence data of C. ulcerans isolate W25 were generated, analyzed and taxonomical relationship to other Corynebacterium species as well as growth properties of the isolate were characterized. The genome of C. ulcerans W25 comprises 2,550,924 bp with a G+C content of 54.41% and a total of 2376 genes.

scholarly journals Isolation and Characterization of Small Extracellular Vesicles from Porcine Blood Plasma, Cerebrospinal Fluid, and Seminal Plasma

Proteomes ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 17 ◽  
Author(s):  
Skalnikova ◽  
Bohuslavova ◽  
Turnovcova ◽  
Juhasova ◽  
Juhas ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Blood Plasma ◽  
Extracellular Vesicles ◽  
Seminal Plasma ◽  
Biomedical Research ◽  
Body Fluids ◽  
Large Animal ◽  
Large Animal Models ◽  
Isolation And Characterization ◽  
Proteomic Analyses

Extracellular vesicles (EVs) are a highly attractive subject of biomedical research as possible carriers of nucleic acid and protein biomarkers. EVs released to body fluids enable indirect access to inner organs by so-called “liquid biopsies”. Obtaining a high-quality EV sample with minimum contaminants is crucial for proteomic analyses using LC–MS/MS or other techniques. However, the EV content in various body fluids largely differs, which may hamper subsequent analyses. Here, we present a comparison of extracellular vesicle yields from blood plasma, cerebrospinal fluid, and seminal plasma using an experimental pig model. Pigs are widely used in biomedical research as large animal models with anatomy and physiology close to those of humans and enable studies (e.g., of the nervous system) that are unfeasible in humans. EVs were isolated from body fluids by differential centrifugation followed by ultracentrifugation. EVs were characterized according to protein yields and to the quality of the isolated vesicles (e.g., size distribution, morphology, positivity for exosome markers). In our experimental setting, substantial differences in EV amounts were identified among body fluids, with the seminal plasma being the richest EV source. The yields of pellet proteins from ultracentrifugation of 1 mL of porcine body fluids may help to estimate body fluid input volumes to obtain sufficient samples for subsequent proteomic analyses.

Role of the mitochondrial genome in assisted reproductive technologies and embryonic stem cell-based therapeutic cloning

2004 ◽  
Vol 16 (7) ◽  
pp. 743 ◽  
Author(s):  
Carol A. Brenner ◽  
H. Michael Kubisch ◽  
Kenneth E. Pierce
Keyword(s):  
Nuclear Transfer ◽  
Assisted Reproductive Technologies ◽  
Embryonic Stem ◽  
Direct Consequence ◽  
Reproductive Technologies ◽  
Embryonic Cell ◽  
Therapeutic Cloning ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Heteroplasmy ◽  
Invasive Techniques

Mitochondria play a pivotal role in cellular metabolism and are important determinants of embryonic development. Mitochondrial function and biogenesis rely on an intricate coordination of regulation and expression of nuclear and mitochondrial genes. For example, several nucleus-derived transcription factors, such as mitochondrial transcription factor A, are required for mitochondrial DNA replication. Mitochondrial inheritance is strictly maternal while paternally-derived mitochondria are selectively eliminated during early embryonic cell divisions. However, there are reports from animals as well as human patients that paternal mitochondria can occasionally escape elimination, which in some cases has led to severe pathologies. The resulting existence of different mitochondrial genomes within the same cell has been termed mitochondrial heteroplasmy. The increasing use of invasive techniques in assisted reproduction in humans has raised concerns that one of the outcomes of such techniques is an increase in the incidence of mitochondrial heteroplasmy. Indeed, there is evidence that heteroplasmy is a direct consequence of ooplasm transfer, a technique that was used to ‘rescue’ oocytes from older women by injecting ooplasm from young oocytes. Mitochondria from donor and recipient were found in varying proportions in resulting children. Heteroplasmy is also a byproduct of nuclear transfer, as has been shown in studies on cloned sheep, cattle and monkeys. As therapeutic cloning will depend on nuclear transfer into oocytes and the subsequent generation of embryonic stem cells from resulting blastocysts, the prospect of mitochondrial heteroplasmy and its potential problems necessitate further studies in this area.

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