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      The progress of induced pluripotent stem cells derived from pigs: a mini review of recent advances

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          Abstract

          Pigs ( Sus scrofa) are widely acknowledged as an important large mammalian animal model due to their similarity to human physiology, genetics, and immunology. Leveraging the full potential of this model presents significant opportunities for major advancements in the fields of comparative biology, disease modeling, and regenerative medicine. Thus, the derivation of pluripotent stem cells from this species can offer new tools for disease modeling and serve as a stepping stone to test future autologous or allogeneic cell-based therapies. Over the past few decades, great progress has been made in establishing porcine pluripotent stem cells (pPSCs), including embryonic stem cells (pESCs) derived from pre- and peri-implantation embryos, and porcine induced pluripotent stem cells (piPSCs) using a variety of cellular reprogramming strategies. However, the stabilization of pPSCs was not as straightforward as directly applying the culture conditions developed and optimized for murine or primate PSCs. Therefore, it has historically been challenging to establish stable pPSC lines that could pass stringent pluripotency tests. Here, we review recent advances in the establishment of stable porcine PSCs. We focus on the evolving derivation methods that eventually led to the establishment of pESCs and transgene-free piPSCs, as well as current challenges and opportunities in this rapidly advancing field.

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          Most cited references231

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          Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

          Differentiated cells can be reprogrammed to an embryonic-like state by transfer of nuclear contents into oocytes or by fusion with embryonic stem (ES) cells. Little is known about factors that induce this reprogramming. Here, we demonstrate induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions. Unexpectedly, Nanog was dispensable. These cells, which we designated iPS (induced pluripotent stem) cells, exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Subcutaneous transplantation of iPS cells into nude mice resulted in tumors containing a variety of tissues from all three germ layers. Following injection into blastocysts, iPS cells contributed to mouse embryonic development. These data demonstrate that pluripotent stem cells can be directly generated from fibroblast cultures by the addition of only a few defined factors.
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            Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

            Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.
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              Embryonic stem cell lines derived from human blastocysts.

              Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages. After undifferentiated proliferation in vitro for 4 to 5 months, these cells still maintained the developmental potential to form trophoblast and derivatives of all three embryonic germ layers, including gut epithelium (endoderm); cartilage, bone, smooth muscle, and striated muscle (mesoderm); and neural epithelium, embryonic ganglia, and stratified squamous epithelium (ectoderm). These cell lines should be useful in human developmental biology, drug discovery, and transplantation medicine.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2640782/overviewRole: Role: Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/2719659/overviewRole: Role: Role: Role: Role: Role: Role: Role:
                Role: Role: Role: Role: Role: Role:
                URI : https://loop.frontiersin.org/people/310495/overviewRole: Role: Role: Role: Role: Role:
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                24 June 2024
                2024
                : 12
                : 1371240
                Affiliations
                [1] 1 Department of Biochemistry and Molecular Biology , Cumming School of Medicine , University of Calgary , Calgary, AB, Canada
                [2] 2 Faculty of Veterinary Medicine , University of Calgary , Calgary, AB, Canada
                [3] 3 Reproductive Biology and Regenerative Medicine Research Group , University of Calgary , Calgary, AB, Canada
                [4] 4 Alberta Children’s Hospital Research Institute , Calgary, AB, Canada
                [5] 5 Biomedical Engineering Graduate Program , University of Calgary , Calgary, AB, Canada
                Author notes

                Edited by: Francesco De Francesco, Azienda Ospedaliero Universitaria Ospedali Riuniti, Italy

                Reviewed by: Simin Li, Southern Medical University, China

                *Correspondence: Li-Fang Chu, lifangjack.chu@ 123456ucalgary.ca
                Article
                1371240
                10.3389/fcell.2024.1371240
                11228285
                38979033
                f0fc2f6a-da03-492f-8930-c6ab699040aa
                Copyright © 2024 Neira, Conrad, Rusteika and Chu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 16 January 2024
                : 10 April 2024
                Funding
                The authors declare that financial support was received for the research, authorship, and/or publication of this article. This research was undertaken thanks to funding support from the Faculty of Veterinary Medicine, University of Calgary (UCVM), Alberta Children’s Hospital Research Institute (ACHRI), the Canada Research Chairs Program (CRC, L-FC, 950-232985), Canada Foundation for Innovation (CFI, L-FC, 40653), Natural Sciences and Engineering Research Council of Canada (NSERC, L-FC, RGPIN-2021-02580) and the Government of Canada’s New Frontiers in Research Fund (NFRFE-2020-00446, NFRFE-2023-00170).
                Categories
                Cell and Developmental Biology
                Mini Review
                Custom metadata
                Stem Cell Research

                porcine pluripotent stem cells,cellular reprogramming,induced pluripotent stem cells,embryonic stem cells,transgene-free

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