Large Animal Models for the Clinical Application of Human Induced Pluripotent Stem Cells.
Abstract: Induced pluripotent stem cell (iPSC) technology offers a practically infinite and ethically acceptable source to obtain a variety of somatic cells. Coupled with the biotechnologies of cell therapy or tissue engineering, iPSC technology will enormously contribute to human regenerative medicine. Before clinical application, such human iPSC (hiPSC)-based therapies should be assessed using large animal models that more closely match biological or biomechanical properties of human patients. Therefore, it is critical to generate large animal iPSCs, obtain their iPSC-derived somatic cells, and preclinically evaluate their therapeutic efficacy and safety in large animals. During the past decade, the establishment of iPSC lines of a series of large animal species has been documented, and the acquisition and preclinical evaluation of iPSC-derived somatic cells has also been reported. Despite this progress, significant obstacles, such as obtaining or preserving the bona fide pluripotency of large animal iPSCs, have been encountered. Simultaneously, studies of large animal iPSCs have been overlooked in comparison with those of mouse and hiPSCs, and this field deserves more attention and support due to its important preclinical relevance. Herein, this review will focus on the large animal models of pigs, dogs, horses, and sheep/goats, and summarize current progress, challenges, and potential future directions of research on large animal iPSCs.
Publication Date: 2019-08-28
PubMed ID: 31359827DOI: 10.1089/scd.2019.0136Google Scholar: Lookup
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Summary
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The research article explores the use of large animal models to evaluate the application of human-induced pluripotent stem cells (iPSCs) for regenerative medicine. It summarizes the progress, challenges, and potential future directions of this approach.
Overview of the study on large animal models for iPSC applications
- The research discusses the potential of Induced pluripotent stem cell (iPSC) technology as a rich and ethically acceptable source for obtaining a variety of human somatic cells. This can be paired with cell therapy or tissue engineering technologies to contribute significantly to regenerative medicine.
- The article emphasizes the need for rigorous preclinical testing of iPSC-based therapies on large animal models, as they more closely mimic the biological or biomechanical properties of humans.
- The researchers make note of advancements from the past decade towards the establishment of iPSC lines from various large animal species. Their aim was to assess the therapeutic efficacy and safety of iPSC-derived somatic cells before they can be clinically applied to humans.
Challenges and Future Directions
- Despite notable progress, the researchers point out significant barriers, such as the difficulty in acquiring or maintaining the true pluripotency of large animal iPSCs. True pluripotency refers to the characteristic of stem cells being able to evolve into any cell type in the body.
- The researchers also note that while efforts have been made to advance large animal iPSC research, it has often been overshadowed by the focus on mouse and human iPSCs. They argue that more attention and support should be given to this field due to its direct applicability to preclinical studies, which is vital to moving forward with clinical trials.
- The review specifically highlights progress in large animal iPSC research involving pigs, dogs, horses, and sheep/goats. These animal models represent a realistic platform for assessing the utility of iPSC-based therapies in regenerative medicine.
Recommendations
- The researchers advocate for more robust support and attention to large animal iPSC research, given its potential to contribute immensely to regenerative medicine once the challenges of stem cell pluripotency preservation are overcome.
- This review serves as a call to action for raising the profile of iPSC work in large animals and underscores the critical importance of this field in bringing iPSC-based therapies from concept to clinical application.
Cite This Article
APA
Cong X, Zhang SM, Ellis MW, Luo J.
(2019).
Large Animal Models for the Clinical Application of Human Induced Pluripotent Stem Cells.
Stem Cells Dev, 28(19), 1288-1298.
https://doi.org/10.1089/scd.2019.0136
Publication
Researcher Affiliations
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.
- Department of Cardiology, Bethune First Hospital of Jilin University, Changchun, China.
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.
- Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut.
- Section of Cardiovascular Medicine, Department of Internal Medicine, Yale Cardiovascular Research Center, Yale School of Medicine, New Haven, Connecticut.
- Yale Stem Cell Center, New Haven, Connecticut.
MeSH Terms
- Animals
- Bibliometrics
- Biomarkers / metabolism
- Cell Line
- Cell- and Tissue-Based Therapy / methods
- Dogs
- Goats
- Horses
- Humans
- Induced Pluripotent Stem Cells / cytology
- Induced Pluripotent Stem Cells / physiology
- Mice
- Models, Animal
- Regenerative Medicine / methods
- Sheep
- Species Specificity
- Stem Cell Transplantation / methods
- Swine
- Tissue Engineering / methods
- Treatment Outcome
Citations
This article has been cited 7 times.- Barrachina L, Arshaghi TE, O'Brien A, Ivanovska A, Barry F. Induced pluripotent stem cells in companion animals: how can we move the field forward?. Front Vet Sci 2023;10:1176772.
- Recchia K, Machado LS, Botigelli RC, Pieri NCG, Barbosa G, de Castro RVG, Marques MG, Pessu00f4a LVF, Fantinato Neto P, Meirelles FV, de Souza AF, Martins SMMK, Bressan FF. In vitro induced pluripotency from urine-derived cells in porcine.. World J Stem Cells 2022 Mar 26;14(3):231-244.
- Dobson LK, Zeitouni S, McNeill EP, Bearden RN, Gregory CA, Saunders WB. Canine Mesenchymal Stromal Cell-Mediated Bone Regeneration is Enhanced in the Presence of Sub-Therapeutic Concentrations of BMP-2 in a Murine Calvarial Defect Model.. Front Bioeng Biotechnol 2021;9:764703.
- Gao Y, Pu J. Differentiation and Application of Human Pluripotent Stem Cells Derived Cardiovascular Cells for Treatment of Heart Diseases: Promises and Challenges.. Front Cell Dev Biol 2021;9:658088.
- Kumar D, Talluri TR, Selokar NL, Hyder I, Kues WA. Perspectives of pluripotent stem cells in livestock.. World J Stem Cells 2021 Jan 26;13(1):1-29.
- de Castro RVG, Pieri NCG, Fantinato Neto P, Grizendi BM, Du00f3ria RGS, Meirelles FV, Smith LC, Garcia JM, Bressan FF. In Vitro Induction of Pluripotency from Equine Fibroblasts in 20% or 5% Oxygen.. Stem Cells Int 2020;2020:8814989.
- Gimeno BF, Bariani MV, Laiz-Quiroga L, Martu00ednez-Leu00f3n E, Von-Meyeren M, Rey O, Mutto Au00c1, Osycka-Salut CE. Effects of In Vitro Interactions of Oviduct Epithelial Cells with Frozen-Thawed Stallion Spermatozoa on Their Motility, Viability and Capacitation Status.. Animals (Basel) 2021 Jan 3;11(1).