scholarly journals Beyond the mouse: non-rodent animal models for study of early mammalian development and biomedical research

2019 ◽  
Vol 63 (3-4-5) ◽  
pp. 187-201 ◽  
Author(s):  
Zofia E. Madeja ◽  
Piotr Pawlak ◽  
Anna Piliszek
Keyword(s):  
Biomedical Research ◽  
Embryonic Stem ◽  
Time Frame ◽  
Developmental Time ◽  
Genetically Engineered ◽  
Farm Animals ◽  
Long Term Effects ◽  
Mammalian Development ◽  
Stem Cell Lines

The preimplantation development of mammals generally follows the same plan. It starts with the formation of a totipotent zygote, and through consecutive cleavage divisions and differentiation events leads to blastocyst formation. However, the intervening events may differ between species. The regulation of these processes has been extensively studied in the mouse, which displays some unique features among eutherian mammals. Farm animals such as pigs, cattle, sheep and rabbits share several similarities with one another, and with the human developmental plan. These include the timing of epigenetic reprogramming, the moment of embryonic genome activation and the developmental time-frame. Recently, efficient techniques for genetic modification have been established for large domestic animals. Genome sequences and gene manipulation tools are now available for cattle, pigs, sheep and goats, and a larger number of genetically engineered livestock is now accessible for biomedical research. Yet, these animals still make up less than 0.5% of animals in research, mainly due to our inadequate knowledge of the processes responsible for pluripotency maintenance (to date no stable naïve embryonic stem cell lines have been established) and early development. In this review, we highlight our present knowledge of the key preimplantation events in the 3 non-rodent species which present the highest potential for biomedical research related to early embryonic development: cattle, which offer an excellent model to study human in vitro embryo development, pigs which emerge as models to study the long-term effects of gene-based therapies and rabbits, which in many aspects of embryology resemble the human.

scholarly journals Pancreatic Progenitors and Organoids as a Prerequisite to Model Pancreatic Diseases and Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Meike Hohwieler ◽  
Martin Müller ◽  
Pierre-Olivier Frappart ◽  
Sandra Heller
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Embryonic Stem ◽  
Cell Types ◽  
Genetically Engineered ◽  
Hereditary Diseases ◽  
Pancreatic Diseases ◽  
Pancreatic Progenitors

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are characterized by their unique capacity to stepwise differentiate towards any particular cell type in an adult organism. Pluripotent stem cells provide a beneficial platform to model hereditary diseases and even cancer development. While the incidence of pancreatic diseases such as diabetes and pancreatitis is increasing, the understanding of the underlying pathogenesis of particular diseases remains limited. Only a few recent publications have contributed to the characterization of human pancreatic development in the fetal stage. Hence, most knowledge of pancreatic specification is based on murine embryology. Optimizing and understanding current in vitro protocols for pancreatic differentiation of ESCs and iPSCs constitutes a prerequisite to generate functional pancreatic cells for better disease modeling and drug discovery. Moreover, human pancreatic organoids derived from pluripotent stem cells, organ-restricted stem cells, and tumor samples provide a powerful technology to model carcinogenesis and hereditary diseases independent of genetically engineered mouse models. Herein, we summarize recent advances in directed differentiation of pancreatic organoids comprising endocrine cell types. Beyond that, we illustrate up-and-coming applications for organoid-based platforms.

scholarly journals 173 EFFECT OF CULTURE SYSTEM FOR IVM-IVF PIG EMBRYOS ON THE ICMS ABILITY TO PRODUCE OUTGROWTHS FOR EMBRYONIC STEM CELL DERIVATION

2005 ◽  
Vol 17 (2) ◽  
pp. 237 ◽  
Author(s):  
G. Lazzari ◽  
I. Lagutina ◽  
G. Crotti ◽  
P. Turini ◽  
S. Colleoni ◽  
...  
Keyword(s):  
Cell Mass ◽  
Embryonic Stem ◽  
Farm Animals ◽  
Es Cell ◽  
Blastocyst Formation ◽  
Blastocyst Development ◽  
In Vivo Culture

Attempts to derive true embryonic stem cells in large farm animals rely on the supply of good quality embryos. In these species, including the pig, pre-implantation-stage embryos can be produced by in vitro techniques from slaughterhouse ovaries. The objective of this study was to evaluate the ability of the inner cell masses (ICMs) of pig embryos, produced in vitro by different methods, to provide viable initial outgrowths of ICM cells that could be subsequently subcultured and expanded. Porcine oocytes were recovered from slaughtered donors and matured in vitro for 40–44 h in DMEM-F12 supplemented with 10% FCS, 0.05 IU LH and FSH (Menogon, Ferring, Milan, Italy), 0.3 mM cystine, 0.5 mM cysteamine, 50 ng/mL long-EGF, 100 ng/mL long-IGF1, 5 ng/mL bFGF (Sigma-Aldrich, Milan, Italy) in 5% CO2 at 38.5°C. Boar frozen-thawed semen was separated on a percoll gradient and diluted in TALP medium with PHE (penicillamine, hypotaurine, epinefrine) to a concentration ranging from 0.05 to 0.1 million sperm per mL. Oocytes were partially decumulated, co-incubated with sperm for 24 h, and finally denuded and cultured in microdrops of mSOFaa or NCSU. After cleavage, approximately half of the cleaved embryos were surgically transferred into the sheep oviduct for 4 days of in vivo culture and the remaining embryos were left in vitro in the two media. On Day +6 in vivo-cultured embryos were recovered from the sheep oviduct. Blastocyst formation and quality were comparatively evaluated in the three culture groups. Quality specifically referred to the morphology/size of the ICM according to the following criteria: ICM A (large/prominent), ICM B (flat), and ICM C (non-visible). All embryos with a visible inner cell mass were subjected to microdissection with needles to recover the ICMs that were then plated on feeder-layers of mitomycin-treated STO fibroblasts. Attachment and outgrowth was evaluated 48–72 h post-plating. Results are presented in Table 1. Our data indicate that in vivo culture of pig embryos in the sheep oviduct greatly enhance both blastocyst development and ICM quality. As a consequence the efficiency of outgrowth formation, following plating for ES cell derivation, was significantly higher with ICMs derived from IVM-IVF pig embryos cultured in vivo as compared to their in vitro-cultured counterparts. Within the two culture media tested for in vitro culture, SOF and NCSU, the rate of blastocyst formation was similar but the quality of SOF-cultured embryos is higher. In conclusion, embryo/ICM quality represents a fundamental requirement for the derivation of ES cell lines, and in vivo culture in the sheep oviduct provides the most efficient source of high quality IVM-IVF pig embryos. Table 1. Blastocyst development and ICM quality of in vitro-produced pig embryos This work was supported by the Istituto Superiore di Sanità, Programma Nazionale Cellule Staminali, Rome, Italy, grant No. CS 11.

scholarly journals Derivation of new human embryonic stem cell lines reveals rapid epigenetic progression in vitro that can be prevented by chemical modification of chromatin

2011 ◽  
Vol 21 (4) ◽  
pp. 751-764 ◽  
Author(s):  
Silvia V. Diaz Perez ◽  
Rachel Kim ◽  
Ziwei Li ◽  
Victor E. Marquez ◽  
Sanjeet Patel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chemical Modification ◽  
Embryonic Stem Cell ◽  
Cell Lines ◽  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Stem Cell Lines

Pluripotent Stem Cells and Reprogrammed Cells in Farm Animals

2011 ◽  
Vol 17 (4) ◽  
pp. 474-497 ◽  
Author(s):  
Monika Nowak-Imialek ◽  
Wilfried Kues ◽  
Joseph W. Carnwath ◽  
Heiner Niemann
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Germ Line ◽  
Embryonic Stem ◽  
Domestic Animals ◽  
Farm Animals ◽  
Pluripotent Cells ◽  
Cell Extracts

AbstractPluripotent cells are unique because of their ability to differentiate into the cell lineages forming the entire organism. True pluripotent stem cells with germ line contribution have been reported for mice and rats. Human pluripotent cells share numerous features of pluripotentiality, but confirmation of their in vivo capacity for germ line contribution is impossible due to ethical and legal restrictions. Progress toward derivation of embryonic stem cells from domestic species has been made, but the derived cells were not able to produce germ line chimeras and thus are termed embryonic stem-like cells. However, domestic animals, in particular the domestic pig (Sus scrofa), are excellent large animals models, in which the clinical potential of stem cell therapies can be studied. Reprogramming technologies for somatic cells, including somatic cell nuclear transfer, cell fusion, in vitro culture in the presence of cell extracts, in vitro conversion of adult unipotent spermatogonial stem cells into germ line derived pluripotent stem cells, and transduction with reprogramming factors have been developed with the goal of obtaining pluripotent, germ line competent stem cells from domestic animals. This review summarizes the present state of the art in the derivation and maintenance of pluripotent stem cells in domestic animals.

scholarly journals SOX17 Is Not Required for the Derivation and Maintenance of Mouse Extraembryonic Endoderm Stem Cell Lines

2022 ◽  
Author(s):  
Xudong Dong ◽  
Ailing Ding ◽  
Jiangwei Lin
Keyword(s):  
Stem Cell ◽  
Cell Lines ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Preimplantation Embryos ◽  
Primitive Endoderm ◽  
Extraembryonic Endoderm ◽  
Gene Expression Analyses ◽  
Stem Cell Lines

Extraembryonic endoderm stem (XEN) cell lines can be derived and maintained in vitro and reflect the primitive endoderm cell lineage. SOX17 is thought to be required for the derivation and maintenance of mouse XEN cell lines. Here we have re-evaluated this requirement for SOX17. We derived multiple SOX17-deficient XEN cell lines from preimplantation embryos of a SOX17-Cre knockout strain and chemically converted multiple SOX17-deficient embryonic stem cell lines into XEN cell lines by transient culturing with retinoic acid and Activin A. We confirmed the XEN profile of SOX17-deficient cell lines by immunofluorescence with various markers, by NanoString gene expression analyses, and by their contribution to the extraembryonic endoderm of chimeric embryos produced by injecting these cells into blastocysts. Thus, SOX17 is not required for the derivation and maintenance of XEN cell lines.

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.

Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro

10.1038/74447 ◽  
2000 ◽  
Vol 18 (4) ◽  
pp. 399-404 ◽  
Author(s):  
Benjamin E. Reubinoff ◽  
Martin F. Pera ◽  
Chui-Yee Fong ◽  
Alan Trounson ◽  
Ariff Bongso
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cell Lines ◽  
Embryonic Stem ◽  
Stem Cell Lines

scholarly journals Derivation of Two New Human Embryonic Stem Cell Lines from Nonviable Human Embryos

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Svetlana Gavrilov ◽  
Darja Marolt ◽  
Nataki C. Douglas ◽  
Robert W. Prosser ◽  
Imran Khalid ◽  
...  
Keyword(s):  
Human Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Poor Quality ◽  
Human Embryos ◽  
Clinical Use ◽  
Stem Cell Lines ◽  
Hesc Lines ◽  
Hesc Derivation

We report the derivation and characterization of two new human embryonic stem cells (hESC) lines (CU1 and CU2) from embryos with an irreversible loss of integrated organismic function. In addition, we analyzed retrospective data of morphological progression from embryonic day (ED) 5 to ED6 for 2480 embryos not suitable for clinical use to assess grading criteria indicative of loss of viability on ED5. Our analysis indicated that a large proportion ofin vitrofertilization (IVF) embryos not suitable for clinical use could be used for hESC derivation. Based on these combined findings, we propose that criteria commonly used in IVF clinics to determine optimal embryos for uterine transfer can be employed to predict the potential for hESC derivation from poor quality embryos without the destruction of vital human embryos.

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