Equine Induced Pluripotent Stem Cells have a Reduced Tendon Differentiation Capacity Compared to Embryonic Stem Cells.
Abstract: Tendon injuries occur commonly in horses and their repair through scar tissue formation predisposes horses to a high rate of re-injury. Pluripotent stem cells may provide a cell replacement therapy to improve tendon tissue regeneration and lower the frequency of re-injury. We have previously demonstrated that equine embryonic stem cells (ESCs) differentiate into the tendon cell lineage upon injection into the damaged horse tendon and can differentiate into functional tendon cells in vitro to generate artificial tendons. Induced pluripotent stem cells (iPSCs) have now been derived from horses but, to date, there are no reports on their ability to differentiate into tendon cells. As iPSCs can be produced from adult cell types, they provide a more accessible source of cells than ESCs, which require the use of horse embryos. The aim of this study was to compare tendon differentiation by ESCs and iPSCs produced through two independent methods. In two-dimensional differentiation assays, the iPSCs expressed tendon-associated genes and proteins, which were enhanced by the presence of transforming growth factor-β3. However, in three-dimensional (3D) differentiation assays, the iPSCs failed to differentiate into functional tendon cells and generate artificial tendons. These results demonstrate the utility of the 3D in vitro tendon assay for measuring tendon differentiation and the need for more detailed studies to be performed on equine iPSCs to identify and understand their epigenetic differences from pluripotent ESCs prior to their clinical application.
Publication Date: 2015-11-16 PubMed ID: 26664982PubMed Central: PMC4672282DOI: 10.3389/fvets.2015.00055Google Scholar: Lookup
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Summary
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The study investigates the viability of using induced pluripotent stem cells (iPSCs) from horses to repair tendon injuries. It showed that while these cells can show characteristics of tendon-associated genes and proteins, they were unable to successfully differentiate into functional tendon cells and create artificial tendons like their embryonic stem cell (ESCs) counterparts.
The Research Context
- Horses frequently suffer from tendon injuries that often heal with scar tissue, making them susceptible to re-injury.
- A potential therapeutic approach to improve tendon tissue regeneration and reduce re-injury rates might involve the use of pluripotent stem cells.
- Previously, the study team demonstrated that equine embryonic stem cells (ESCs) could differentiate into tendon cells and form functional artificial tendons in vitro.
- Induced pluripotent stem cells (iPSCs), which are derived from adult cells, present a more accessible source of cells than ESCs, which require horse embryos.
- The main aim of the study was to compare the ability of ESCs and iPSCs to differentiate into tendon cells.
In-depth Study Findings
- The researchers carried out two types of differentiation assays – two-dimensional (conventional cell culture techniques) and three-dimensional (3D).
- In the two-dimensional assays, iPSCs indicated expression of tendon-associated genes and proteins, particularly when the growth factor transforming growth factor-β3 was present.
- However, in the three-dimensional assays, which more fully replicated the physical and biochemical environment of a tendon, iPSCs failed to differentiate into functional tendon cells and generate artificial tendons.
- This difference between the outcomes of 2D and 3D assays underscored the importance of a 3D in vitro tendon assay for examining tendon differentiation.
Conclusion and Future Considerations
- The findings revealed important distinctions between iPSCs and ESCs in terms of differentiation into functional tendon cells.
- While iPSCs did express tendon-associated genes and proteins under certain circumstances, they did not differentiate into functional tendon cells or generate artificial tendons in a three-dimensional environment.
- This suggests a need to investigate the epigenetic differences between iPSCs and pluripotent ESCs in greater detail before iPSCs derived from horses can be effectively used in clinical application for tendon repair.
Cite This Article
APA
Bavin EP, Smith O, Baird AE, Smith LC, Guest DJ.
(2015).
Equine Induced Pluripotent Stem Cells have a Reduced Tendon Differentiation Capacity Compared to Embryonic Stem Cells.
Front Vet Sci, 2, 55.
https://doi.org/10.3389/fvets.2015.00055 Publication
Researcher Affiliations
- Centre for Preventive Medicine, Animal Health Trust , Newmarket , UK.
- Département de biomédecine vétérinaire, Faculté de médecine vétérinaire, Université de Montréal , Saint-Hyacinthe, QC , Canada.
- Centre for Preventive Medicine, Animal Health Trust , Newmarket , UK.
- Département de biomédecine vétérinaire, Faculté de médecine vétérinaire, Université de Montréal , Saint-Hyacinthe, QC , Canada.
- Centre for Preventive Medicine, Animal Health Trust , Newmarket , UK.
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