Biocompatible Three-Dimensional Printed Thermoplastic Scaffold for Osteoblast Differentiation of Equine Induced Pluripotent Stem Cells

Baird, Arabella; Falcon, Noelia Dominguez; Saeed, Aram; Guest, Deborah J.

doi:10.1089/ten.tec.2018.0343

Cited by 8 publications

(8 citation statements)

References 45 publications

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“… 2015 ; Baird et al . 2018 , 2019 ). We have previously demonstrated that this method of reprogramming generates karyotypically normal iPSCs (Bavin et al .…”

Section: Discussionmentioning

confidence: 99%

Equine induced pluripotent stem cells are responsive to inflammatory cytokines before and after differentiation into musculoskeletal cell types

Palomino Lago,

Jelbert,

Baird

et al. 2023

In Vitro Cell.Dev.Biol.-Animal

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Persistent inflammation is associated with the poor regeneration of musculoskeletal tissues. Embryonic stem cells (ESCs) have an attenuated response to inflammatory cytokines, but there are mixed reports on the response of induced pluripotent stem cells (iPSCs) to inflammation. Horses provide a relevant large animal model for studying musculoskeletal tissue diseases and the testing of novel therapies. The aim of this study was to determine if equine iPSCs are responsive to the inflammatory cytokines IL-1β, TNFα and IFN-γ in their undifferentiated state, or following differentiation into tendon and cartilage-like cells. We demonstrated that in undifferentiated iPSCs, the cytokines induce NF-κB P65 and STAT1 nuclear translocation which leads to cell death, decreased OCT4 expression and increased expression of inflammatory genes. Following differentiation towards cartilage-like cells exposure to the cytokines resulted in STAT1 nuclear translocation, changes in cartilage gene expression and increased expression of matrix metalloproteinases (MMPs) and inflammatory genes. Exposure of iPSC-derived tendon-like cells to the cytokines resulted nuclear translocation of NF-κB P65 and STAT1, altered tendon gene expression, increased MMP expression and increased expression of inflammatory genes. Equine iPSCs are therefore capable of responding to inflammatory stimulation and this may have relevance for their future clinical application.

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“… 2015 ; Baird et al . 2018 , 2019 ). We have previously demonstrated that this method of reprogramming generates karyotypically normal iPSCs (Bavin et al .…”

Section: Discussionmentioning

confidence: 99%

Equine induced pluripotent stem cells are responsive to inflammatory cytokines before and after differentiation into musculoskeletal cell types

Palomino Lago,

Jelbert,

Baird

et al. 2023

In Vitro Cell.Dev.Biol.-Animal

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“…For instance, equine iPSCs have been differentiated in vitro into neurons, keratinocytes, myocytes, tenocytes, osteoblasts and chondrocytes. However, only neurons and myocytes have shown functional properties such as depolarization and contraction (128,134). Equine tenocytes are apparently challenging to obtain (127) but mechanical loading can improve differentiation (63), and osteoblasts derivation can be promoted in 3D scaffolds that would also facilitate clinical application (129).…”

Section: Ipsc-derived Cells In Companion Animalsmentioning

confidence: 99%

“…When it comes to the applicability of iPSCs in companion animals, reports are scarcer than for their generation and mainly focus on therapeutics or disease modeling. Therapeutic use of iPSCs has been mainly proposed for musculoskeletal conditions in horses ( 60 – 63 , 88 , 127 – 129 ) and for neurological and cardiovascular conditions in dogs ( 67 , 95 , 130 – 133 ). In terms of disease modeling, equine iPSCs can also be used for neurological conditions ( 58 , 134 ).…”

Section: Applications Of Ipscs In Companion Animalsmentioning

confidence: 99%

“…In equines, based on the interest in treating recurrent sport injuries, the majority of studies focused on generating iPSC-derived cell types clinically relevant for musculoskeletal and wound healing injuries. In this regard, equine iPSCs have been differentiated into several cell types including osteoblasts ( 129 ), chondrocytes ( 60 ), tenocytes ( 62 , 63 , 127 ), myocytes ( 128 ), and keratinocytes ( 85 ). In spite of the in vitro evidence of iPSC differentiation potential, the functionality of the obtained cells has only been demonstrated to certain extents and would need to be further tested in the clinical setting.…”

Section: Applications Of Ipscs In Companion Animalsmentioning

confidence: 99%

“…However, only neurons and myocytes have shown functional properties such as depolarization and contraction ( 128 , 134 ). Equine tenocytes are apparently challenging to obtain ( 127 ) but mechanical loading can improve differentiation ( 63 ), and osteoblasts derivation can be promoted in 3D scaffolds that would also facilitate clinical application ( 129 ). Obtainment of chondrocytes from equine iPSCs has been limited and non-conclusive.…”

Section: Applications Of Ipscs In Companion Animalsmentioning

confidence: 99%

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Induced pluripotent stem cells in companion animals: how can we move the field forward?

et al. 2023

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Following a one medicine approach, the development of regenerative therapies for human patients leads to innovative treatments for animals, while pre-clinical studies on animals provide knowledge to advance human medicine. Among many different biological products under investigation, stem cells are among the most prominent. Mesenchymal stromal cells (MSCs) are extensively investigated, but they present challenges such as senescence and limited differentiation ability. Embryonic stem cells (ESCs) are pluripotent cells with a virtually unlimited capacity for self-renewal and differentiation, but the use of embryos carries ethical concerns. Induced pluripotent stem cells (iPSCs) can overcome all of these limitations, as they closely resemble ESCs but are derived from adult cells by reprogramming in the laboratory using pluripotency-associated transcription factors. iPSCs hold great potential for applications in therapy, disease modeling, drug screening, and even species preservation strategies. However, iPSC technology is less developed in veterinary species compared to human. This review attempts to address the specific challenges associated with generating and applying iPSCs from companion animals. Firstly, we discuss strategies for the preparation of iPSCs in veterinary species and secondly, we address the potential for different applications of iPSCs in companion animals. Our aim is to provide an overview on the state of the art of iPSCs in companion animals, focusing on equine, canine, and feline species, as well as to identify which aspects need further optimization and, where possible, to provide guidance on future advancements. Following a “step-by-step” approach, we cover the generation of iPSCs in companion animals from the selection of somatic cells and the reprogramming strategies, to the expansion and characterization of iPSCs. Subsequently, we revise the current applications of iPSCs in companion animals, identify the main hurdles, and propose future paths to move the field forward. Transferring the knowledge gained from human iPSCs can increase our understanding in the biology of pluripotent cells in animals, but it is critical to further investigate the differences among species to develop specific approaches for animal iPSCs. This is key for significantly advancing iPSC application in veterinary medicine, which at the same time will also allow gaining pre-clinical knowledge transferable to human medicine.

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Equine induced pluripotent stem cells

Guest

2021

iPSCs From Diverse Species

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Biocompatible Three-Dimensional Printed Thermoplastic Scaffold for Osteoblast Differentiation of Equine Induced Pluripotent Stem Cells

Cited by 8 publications

References 45 publications

Equine induced pluripotent stem cells are responsive to inflammatory cytokines before and after differentiation into musculoskeletal cell types

Equine induced pluripotent stem cells are responsive to inflammatory cytokines before and after differentiation into musculoskeletal cell types

Induced pluripotent stem cells in companion animals: how can we move the field forward?

Equine induced pluripotent stem cells

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