Differentiation of equine induced pluripotent stem cells into mesenchymal lineage for therapeutic use.
Abstract: In previous work, we established an equine induced pluripotent stem cell line (E-iPSCs) from equine adipose-derived stem cells (ASCs) using a lentiviral vector encoding four transcription factors: Oct4, Sox2, Klf4, and c-Myc. In the current study, we attempted to differentiate these established E-iPSCs into mesenchymal stem cells (MSCs) by serial passaging using MSC-defined media for stem cell expansion. Differentiation of the MSCs was confirmed by analyzing expression levels of the MSC surface markers CD44 and CD29, and the pluripotency markers Nanog and Oct4. Results indicated that the E-iPSC-derived MSCs (E-iPSC-MSCs) retained the characteristics of MSCs, including the ability to differentiate into chondrogenic, osteogenic, or myogenic lineages. E-iPSC-MSCs were rendered suitable for therapeutic use by inhibiting immune rejection through exposure to transforming growth factor beta 2 (TGF-β2) in culture, which down-regulated the expression of major histocompatibility complex class I (MHC class I) proteins that cause immune rejection if they are incompatible with the MHC antigen of the recipient. We reported 16 cases of E-iPSC-MSC transplantations into injured horses with generally positive effects, such as reduced lameness and fraction lines. Our findings indicate that E-iPSC-MSCs can demonstrate MSC characteristics and be safely and practically used in the treatment of musculoskeletal injuries in horses.
Publication Date: 2019-09-11 PubMed ID: 31505996PubMed Central: PMC6791704DOI: 10.1080/15384101.2019.1664224Google Scholar: Lookup
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- Journal Article
- Biotechnology
- Cell Culture
- Cell Proliferation
- Equine Diseases
- Equine Health
- Equine model
- Equine Science
- Genetics
- Horses
- Immunology
- In Vitro Research
- Major Histocompatibility Complex (MHC)
- Mesenchymal Cells
- Musculoskeletal System
- Stem Cells
- Therapeutic Intervention
- Veterinary Care
- Veterinary Medicine
- Veterinary Research
Summary
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This research explores the differentiation of horse-induced pluripotent stem cells into mesenchymal stem cells for therapeutic application, notably for treating musculoskeletal injuries in horses. Results indicated positive outcomes when transplanted into injured horses.
Introduction to the Study
- This research was a continuation of an earlier study that established an equine induced pluripotent stem cell line (E-iPSCs) using equine adipose-derived stem cells (ASCs). In this study, the researchers attempt to differentiate these stem cells into mesenchymal stem cells (MSCs).
- The importance of this research lies in its potential for therapeutic applications, particularly for the treatment of musculoskeletal injuries in horses. Stem cell therapies hold great promise in the field of regenerative medicine due to their ability to replace damaged cells and promote tissue regeneration.
Methodology and Results
- Differentiation was achieved by serial passaging using a specific media designed for MSCs. The researchers checked for successful differentiation by assessing the presence of characteristic MSC markers CD44 and CD29, while looking for the absence of pluripotency markers like Nanog and Oct4. This was necessary to ensure that the stem cells had differentiated successfully into the intended MSCs.
- Results showed that the E-iPSC-derived MSCs retained the characteristics of MSCs. This includes their ability to further differentiate into different types of cells such as cartilage cells (chondrogenic), bone cells (osteogenic), or muscle cells (myogenic). The retaining of these characteristics is critical to their usefulness in therapeutic applications.
- The researchers also took measures to make E-iPSC-MSCs suitable for transplantation. This was achieved by exposing the cells to a substance called transforming growth factor beta 2 (TGF-β2), which reduced their expression of MHC class I proteins. These proteins can potentially cause immune rejection if transplanted, as they may be incompatible with the recipient’s immune system.
Therapeutic Applications and Conclusion
- The study reports the transplantation of these E-iPSC-MSCs into 16 injured horses. Reported improvements included reduced limpness and fraction lines, suggesting a promising role for E-iPSC-MSCs in treating musculoskeletal injuries in horses.
- Overall, the findings indicate that E-iPSC-MSCs can mimic MSC characteristics and potentially be safely and effectively used for therapeutic applications in horses. This is a significant finding that contributes to the on-going development of regenerative medicine techniques in the veterinary field.
Cite This Article
APA
Chung MJ, Park S, Son JY, Lee JY, Yun HH, Lee EJ, Lee EM, Cho GJ, Lee S, Park HS, Jeong KS.
(2019).
Differentiation of equine induced pluripotent stem cells into mesenchymal lineage for therapeutic use.
Cell Cycle, 18(21), 2954-2971.
https://doi.org/10.1080/15384101.2019.1664224 Publication
Researcher Affiliations
- College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.
- Stem Cell Therapeutic Research Institute, Kyungpook National University , Daegu , Republic of Korea.
- College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.
- Stem Cell Therapeutic Research Institute, Kyungpook National University , Daegu , Republic of Korea.
- College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.
- Stem Cell Therapeutic Research Institute, Kyungpook National University , Daegu , Republic of Korea.
- College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.
- Stem Cell Therapeutic Research Institute, Kyungpook National University , Daegu , Republic of Korea.
- College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.
- Stem Cell Therapeutic Research Institute, Kyungpook National University , Daegu , Republic of Korea.
- College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.
- College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.
- College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.
- Cell Engineering For Origin , Seoul , Republic of Korea.
- Cell Engineering For Origin , Seoul , Republic of Korea.
- College of Veterinary Medicine, Kyungpook National University , Daegu , Republic of Korea.
- Stem Cell Therapeutic Research Institute, Kyungpook National University , Daegu , Republic of Korea.
MeSH Terms
- Adipocytes / cytology
- Adipose Tissue / cytology
- Animals
- Bone Development / physiology
- Cell Differentiation / physiology
- Cell- and Tissue-Based Therapy / methods
- Cells, Cultured
- Chondrocytes / cytology
- Chondrogenesis / physiology
- Graft Rejection / immunology
- Graft Rejection / prevention & control
- Horses
- Induced Pluripotent Stem Cells / cytology
- Kruppel-Like Factor 4
- Mesenchymal Stem Cell Transplantation / methods
- Mesenchymal Stem Cells / cytology
- Muscle Cells / cytology
- Muscle Development / physiology
- Muscle, Skeletal / injuries
- Osteocytes / cytology
- Transforming Growth Factor beta2 / metabolism
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Citations
This article has been cited 6 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.
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