Generation, Characterization, and Multilineage Potency of Mesenchymal-Like Progenitors Derived from Equine Induced Pluripotent Stem Cells.
Abstract: Multipotent mesenchymal stromal cells (MSCs) are more and more frequently used to treat orthopedic injuries in horses. However, these cells are limited in their expandability and differentiation capacity. Recently, the first equine-induced pluripotent stem cell (iPSC) lines were reported by us [ 1 ]. In vitro differentiation of iPSCs into MSC-like cells is an attractive alternative to using MSCs derived from other sources, as a much larger quantity of patient-specific cells with broad differentiation potential could be generated. However, the differentiation capacity of iPSCs to MSCs and the potential for use in tissue engineering have yet to be explored. In this study, equine iPSCs were induced to differentiate into an MSC-like population. Upon induction, the iPSCs changed morphology toward spindle-shaped cells similar to MSCs. The ensuing iPSC-MSCs exhibited downregulation of pluripotency-associated genes and an upregulation of MSC-associated genes. In addition, the cells expressed the same surface markers as MSCs derived from equine umbilical cord blood. We then assessed the multilineage differentiation potential of iPSC-MSCs. Although chondrogenesis was not achieved after induction with transforming growth factor-beta 3 (TGFβ3) and/or bone morphogenic protein 4 (BMP-4) in 3D pellet culture, mineralization characteristic of osteogenesis and lipid droplet accumulation characteristic of adipogenesis were observed after chemical induction. We demonstrate a protocol for the derivation of MSC-like progenitor populations from equine iPS cells.
Publication Date: 2015-11-05 PubMed ID: 26414480DOI: 10.1089/scd.2014.0409Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study discusses the generation of mesenchymal-like progenitors from horse pluripotent stem cells. These cells are similar to stromal cells found in bone marrow, which are often used in equine orthopedic treatments. The research team was able to manipulate the pluripotent stem cells to differentiate them into an analogous cell type – a process that promises to yield a larger pool of cells for medical use.
Generating Mesenchymal-Like Progenitors from Induced Pluripotent Stem Cells
- This research is working on a solution to a challenge in equine orthopedic treatments using multipotent mesenchymal stromal cells (MSCs): these cells have limited expandability and differentiation capacity.
- This limitation led the researchers to explore the possibility of generating mesenchymal-like progenitors from induced pluripotent stem cells (iPSCs).
- iPSCs hold great potential because of their ability to differentiate into nearly any type of cell, which means that a large quantity of patient-specific cells can be generated.
- The research team have induced the iPSCs to differentiate resulting in cells that are morphologically similar to MSCs. The generated cells also exhibit a downregulation of pluripotent genes and an upregulation of MSC-associated genes.
Characterization of the iPSC-MSCs
- The new cells were further characterized by the presence of surface markers similar to those of MSCs derived from equine umbilical cord blood.
- This similarity confirms that the new cells are indeed MSCs.
- The research also assessed whether these new cells have the same multilineage differentiation potential as MSCs, which are capable of differentiating into various types of cells.
- While they noticed that chondrogenesis (formation of cartilage) was not achieved even after chemical induction, they did observe mineralization, characteristic of osteogenesis (bone formation), and lipid droplet accumulation, indicating adipogenesis (fat cell formation).
Potency of the iPSC-MSCs
- Despite the challenges, the researchers were able to demonstrate a protocol for deriving mesenchymal-like progenitors from equine iPS cells.
- This process, once fine-tuned and improved, has potential value in the field of therapeutic treatments for equine orthopedic injuries.
- More research, however, is required to fully understand and utilize the potential of these generated MSC-like cells.
Cite This Article
APA
Lepage SI, Nagy K, Sung HK, Kandel RA, Nagy A, Koch TG.
(2015).
Generation, Characterization, and Multilineage Potency of Mesenchymal-Like Progenitors Derived from Equine Induced Pluripotent Stem Cells.
Stem Cells Dev, 25(1), 80-89.
https://doi.org/10.1089/scd.2014.0409 Publication
Researcher Affiliations
- 1 Department of Biomedical Sciences, University of Guelph , Guelph, Ontario, Canada .
- 2 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital , Toronto, Ontario, Canada .
- 2 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital , Toronto, Ontario, Canada .
- 3 Institute of Biomaterials and Biomedical Engineering, University of Toronto , Toronto, Ontario, Canada .
- 4 Pathology and Experimental Medicine, Mount Sinai Hospital , Toronto, Ontario, Canada .
- 2 Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital , Toronto, Ontario, Canada .
- 5 Department of Obstetrics and Gynecology and Institute of Medical Science, University of Toronto , Toronto, Ontario, Canada .
- 1 Department of Biomedical Sciences, University of Guelph , Guelph, Ontario, Canada .
- 6 Department of Clinical Studies, Orthopedic Research Lab, Aarhus University , Aarhus, Denmark .
MeSH Terms
- Adipogenesis / physiology
- Animals
- Cell Culture Techniques / veterinary
- Cell Differentiation
- Cell Separation
- Cells, Cultured
- Cellular Reprogramming
- Chondrogenesis / physiology
- Horses
- Induced Pluripotent Stem Cells / cytology
- Induced Pluripotent Stem Cells / physiology
- Mesenchymal Stem Cells / cytology
- Mesenchymal Stem Cells / physiology
- Mice
- Osteogenesis / physiology
- Tissue Engineering / veterinary
Grant Funding
- MOP102575 / Canadian Institutes of Health Research
Citations
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- Lu Y, Kats ER, Hines SE, Shang J, Kamijo S, Liu JJ, Liu S, Hogan MV, Lin H. Long-term evaluation of human iPSC-derived cartilage for repairing chondral defects. NPJ Regen Med 2025 Dec 25;11(1):3.
- Weeratunga P, Harman RM, Jager MC, Van de Walle GR. Footprint-free induced pluripotent stem cells can be successfully differentiated into mesenchymal stromal cells in the feline model. Stem Cell Res Ther 2025 Apr 20;16(1):195.
- Roberts EL, Abraham BD, Dang T, Gysel E, Mehrpouyan S, Alizadeh AH, Koch TG, Kallos MS. Computer controlled expansion of equine cord blood mesenchymal stromal cells on microcarriers in 3 L vertical-wheel(®) bioreactors. Front Bioeng Biotechnol 2023;11:1250077.
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