Transcriptional Factors Related to Cellular Kinetics, Apoptosis, and Tumorigenicity in Equine Adipose-Derived Mesenchymal Stem Cells (ASCs) Are Influenced by the Age of the Donors.
Abstract: The impact of donor age on Adipose-derived mesenchymal stem cell (ASC) functionality and safety remains insufficiently characterized, particularly in equine models. This study investigates the influence of age on ASCs proliferation dynamics and the expression of tumorigenic and apoptosis-related markers. Equine ASCs were isolated from juvenile (<5 years), middle-aged (5-15 years), and geriatric (>15 years) horses and assayed across multiple passages. The relative mRNA expressions of pluripotency (Oct4), tumorigenic (CA9), and apoptosis-related (Bax and Bcl 2) markers were evaluated. The Gompertz growth model, population doubling time (PDT), and tissue non-specific ALP activity also followed. The expression of pluripotency and tumorigenic markers showed passage-dependent up-regulation, raising concerns about prolonged culture expansion. Apoptotic regulation displayed a shift with aging, as evidenced by alterations in the Bax/Bcl2 ratio, suggesting compromised cell survival in older ASCs. An age-associated decline in proliferation rates was established, as evidenced by declining alkaline phosphatase (ALP) activity. These findings underscore the necessity for stringent age-based selection criteria in equine stem cell therapies and the challenges associated with using autologous stem cells for regenerative therapies in aged horses. Future research should focus on molecular interventions to mitigate age-related functional decline, ensuring the safety and efficacy of ASCs-based regenerative medicine in equine practice.
Publication Date: 2025-06-28 PubMed ID: 40646808PubMed Central: PMC12249217DOI: 10.3390/ani15131910Google Scholar: Lookup
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Summary
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This research article examines the impact of donor age on the functioning and safety of Adipose-derived mesenchymal stem cells (ASCs) using equine models. The study specifically analyses how age influences cell proliferation, and how tumorigenic and apoptosis-related markers are expressed.
Introduction
- The premise of the study is based on previous understanding that the functions of Adipose-derived mesenchymal stem cells (ASCs) are affected by the age of the donor animal. However, this relationship hasn’t been sufficiently explored, particularly in equine models.
- To address this gap, the researchers sought to examine the influence of age on ASC proliferation, as well as the expression of tumorigenic (cancer-causing) and apoptosis-related (regulating cell death) markers in these cells.
Methods
- The study used equine ASCs harvested from three categories of horses: juveniles (less than 5 years old), middle-aged (5-15 years), and geriatric (over 15 years).
- These harvested ASCs were then subjected to multiple passages (or cycles of growth in a lab setting).
- The researchers evaluated the relative mRNA expressions of pluripotency (via a marker called Oct4), tumorigenicity (through the marker CA9), and of apoptosis-regulation (via markers Bax and Bcl2).
- Additional parameters such as the Gompertz growth model, a statistical representation of growth over time, and population doubling time (PDT), signifying rate of proliferation, were also considered. Tissue non-specific ALP activity, indicating vital cellular processes, was monitored as well.
Findings
- The study found that expression of pluripotency and tumorigenic markers showed an increase with each passage. This implies possible safety concerns with prolonged lab culture of these cells.
- The regulation of apoptosis (cell death) altered with the age of the horse from which ASCs were derived. These changes were evident in the varying Bax/Bcl2 ratio, hinting at compromised cell survival in ASCs from older horses.
- Lastly, the research established a decline in proliferation rates with increasing horse age, as shown by decreased alkaline phosphatase (ALP) activity.
- The authors of the study argue these findings highlight the need for stricter age-based selection criteria when employing stem cells in equine therapy. They also flag the challenges of using autologous stem cells (those derived from the same individual receiving the therapy) in regenerative treatments for older horses.
Future Implications
- The researchers suggest future studies aim at exploring molecular interventions that can help offset the functional decline seen in ASCs with donor age.
- Such research could enhance the safety and effectiveness of regenerative therapies based on ASCs in equine medicine.
Cite This Article
APA
Vachkova E, Arnhold S, Petrova V, Heimann M, Koynarski T, Simeonova G, Piperkov P.
(2025).
Transcriptional Factors Related to Cellular Kinetics, Apoptosis, and Tumorigenicity in Equine Adipose-Derived Mesenchymal Stem Cells (ASCs) Are Influenced by the Age of the Donors.
Animals (Basel), 15(13), 1910.
https://doi.org/10.3390/ani15131910 Publication
Researcher Affiliations
- Department of Pharmacology, Animal Physiology, Biochemistry and Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria.
- Institute of Veterinary Anatomy, Histology and Embryology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
- Department of Pharmacology, Animal Physiology, Biochemistry and Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria.
- Institute of Veterinary Anatomy, Histology and Embryology, Justus-Liebig-University of Giessen, 35392 Giessen, Germany.
- Department of General Animal Husbandry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria.
- Department of Veterinary Surgery, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria.
- Department of Mathematical Analysis and Applications, Faculty of Mathematics and Informatics, University of Veliko Tarnovo, 5003 Veliko Tarnovo, Bulgaria.
Grant Funding
- Project N 9/23 / Faculty of Veterinary Medicine, Trakia University, Stara Zagora, Bulgaria
- grant No.WE 4319/4-1 / German Research Foundation (DFG)
- grant No. AR 333/11-1 / German Research Foundation (DFG)
Conflict of Interest Statement
The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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