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Donor age effects on in vitro chondrogenic and osteogenic differentiation performance of equine bone marrow- and adipose tissue-derived mesenchymal stromal cells.
Abstract: Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stromal cells (MSCs) have shown potential as cell-based therapies for cartilage and bone injuries and are used increasingly in human and veterinary practice to facilitate the treatment of orthopedic conditions. However, human and rodent studies have documented a sharp decline in chondrogenic and osteogenic differentiation potential with increasing donor age, which may be problematic for the important demographic of older orthopedic patients. The aim of this study was to identify the effect of donor age on the chondrogenic and osteogenic differentiation performance of equine BM- and AT-MSCs in vitro. BM- and AT-MSCs and dermal fibroblasts (biological negative control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15-17 months), adult (5-8 years), middle-aged (12-18 years), and geriatric (≥ 22 years). Chondrogenic differentiation performance was assessed quantitatively by measuring pellet size, matrix proteoglycan levels, and gene expression of articular cartilage biomarkers. Osteogenic differentiation performance was assessed quantitatively by measuring alkaline phosphatase activity, calcium deposition, and gene expression of bone biomarkers. Results: Chondrogenic and osteogenic differentiation performance of equine BM- and AT-MSCs declined with increasing donor age. BM-MSCs had a higher chondrogenic differentiation performance. AT-MSCs showed minimal chondrogenic differentiation performance in all age groups. For osteogenesis, alkaline phosphatase activity was also higher in BM-MSCs, but BM-MSCs calcium deposition was affected by donor age earlier than AT-MSCs. Chondrogenic and osteogenic differentiation performance of BM-MSCs exhibited a decline as early as between the newborn and yearling samples. Steady state levels of mRNA encoding growth factors, chondrogenic, and osteogenic biomarkers were lower with increasing donor age in both MSC types. Conclusions: The data showed that chondrogenic and osteogenic differentiation performance of equine BM-MSCs declined already in yearlings, and that AT-MSCs showed minimal chondrogenic potential, but were affected later by donor age with regards to osteogenesis (calcium deposition). The results highlight the importance of donor age considerations and MSC selection for cell-based treatment of orthopedic injuries and will help inform clinicians on when to implement or potentially cryopreserve cells. Moreover, the study provides molecular targets affected by donor age.
© 2022. The Author(s).
Publication Date: 2022-11-03 PubMed ID: 36329434PubMed Central: PMC9632053DOI: 10.1186/s12917-022-03475-2Google 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
Summary
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The research article investigates the effects of aging on the ability of horse-derived bone marrow and fat cells to differentiate into cartilage and bone cells. Results showed that this ability decreases with donor age, which has implications for cell-based therapies for bone and cartilage injuries.
Research Objective
The primary goal of this study was to understand how donor age impacts the potential of bone marrow and adipose tissue-derived mesenchymal stromal cells (MSCs) to differentiate into cartilage (chondrogenic) and bone (osteogenic) cells. Prior studies with human and rodent subjects revealed a significant decrease in this potential as donor age increased, prompting concerns for older patients requiring orthopedic care.
Methodology
- Bone marrow MSCs, adipose tissue MSCs, and dermal fibroblasts (as a biological negative control) were collected from horses belonging to five age groups: newborns, yearlings, adults, middle-aged, and geriatric.
- The chondrogenic differentiation performance was quantitively measured via pellet size, matrix proteoglycan levels, and the gene expression of articular cartilage biomarkers.
- The osteogenic differentiation performance was assessed by measuring alkaline phosphatase activity, calcium deposition, and the gene expression of bone biomarkers.
Results
- The study’s data revealed that both chondrogenic and osteogenic differentiation abilities of BM- and AT-MSCs dropped with increasing donor age.
- Bone marrow MSCs demonstrated better chondrogenic performance compared to adipose tissue-derived MSCs, which showed minimal chondrogenic potential across all age groups.
- For osteogenesis, while BM-MSCs had higher alkaline phosphatase activity, it’s calcium deposition was impacted by donor age earlier compared to AT-MSCs.
- BM-MSCs’ differentiation declined between the newborn and yearling age group.
- Steady state levels of mRNA encoding growth factors, chondrogenic, and osteogenic biomarkers were lower with increasing donor age in both MSC types.
Conclusions
This research demonstrated that the ability of equine BM- and AT-MSCs to differentiate into bone and cartilage cells reduces as the donor ages. This information is significant for clinicians who use cell-based therapies to treat orthopedic injuries. This study not only reveals the importance of considering donor age when choosing MSCs but also offers insight into the molecular targets affected by aging.
Cite This Article
APA
Bagge J, Berg LC, Janes J, MacLeod JN.
(2022).
Donor age effects on in vitro chondrogenic and osteogenic differentiation performance of equine bone marrow- and adipose tissue-derived mesenchymal stromal cells.
BMC Vet Res, 18(1), 388.
https://doi.org/10.1186/s12917-022-03475-2 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, University of Copenhagen, Agrovej 8, 2630, Taastrup, Denmark.
- Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, 1400 Nicholasville Rd, Lexington, KY, 40546, USA.
- Department of Veterinary Clinical Sciences, University of Copenhagen, Agrovej 8, 2630, Taastrup, Denmark.
- Department of Veterinary Science, University of Kentucky Veterinary Diagnostic Laboratory, University of Kentucky, 1490 Bull Lea Rd, Lexington, KY, 40511, USA.
- Department of Veterinary Science, Maxwell H. Gluck Equine Research Center, University of Kentucky, 1400 Nicholasville Rd, Lexington, KY, 40546, USA. jnmacleod@uky.edu.
MeSH Terms
- Horses
- Humans
- Animals
- Osteogenesis
- Bone Marrow
- Alkaline Phosphatase
- Calcium / metabolism
- Cells, Cultured
- Mesenchymal Stem Cells
- Cell Differentiation
- Bone Marrow Cells
Conflict of Interest Statement
The authors declare that they have no competing interests.
References
This article includes 70 references
Citations
This article has been cited 11 times.- Bagge J, Hölmich P, Hammer FA, Nehlin JO, Vomstein K, Blønd L, Hölmich LR, Barfod KW. Successful isolation of viable stem cells from cryopreserved microfragmented human adipose tissue from patients with knee osteoarthritis - a comparative study of isolation by tissue explant culture and enzymatic digestion. J Exp Orthop 2023 Mar 23;10(1):31.
- Hart DA. Use of Brain-Derived Stem/Progenitor Cells and Derived Extracellular Vesicles to Repair Damaged Neural Tissues: Lessons Learned from Connective Tissue Repair Regarding Variables Limiting Progress and Approaches to Overcome Limitations. Int J Mol Sci 2023 Feb 8;24(4).
- DeNotta S, McFarlane D. Immunosenescence and inflammaging in the aged horse. Immun Ageing 2023 Jan 6;20(1):2.
- Zhao F, Tang Q, Liu J. Functional impacts of lactylation in Hypoxia‒primed mesenchymal stromal cells. Front Cell Dev Biol 2025;13:1678282.
- Meng Q, Zheng Y, Chen X, Mu J, Li C, Gao Y, Liu W, Wang Y. Mesenchymal Stem Cells Senescence: Mechanism and Rejuvenation Interventions. Int J Med Sci 2025;22(14):3692-3708.
- Heyman E, Olenic M, De Vlieghere E, De Smet S, Devriendt B, Thorrez L, De Schauwer C. Donor age and breed determine mesenchymal stromal cell characteristics. Stem Cell Res Ther 2025 Feb 28;16(1):99.
- Bagge J, Mahmood H, Janes J, Vomstein K, Blønd L, Hölmich LR, Freude K, Nehlin JO, Barfod KW, Hölmich P. Chondrogenic and Osteogenic In Vitro Differentiation Performance of Unsorted and Sorted CD34(+), CD146(+), and CD271(+) Stem Cells Derived from Microfragmented Adipose Tissue of Patients with Knee Osteoarthritis. J Clin Med 2025 Feb 11;14(4).
- Farach-Carson MC, Wu D, França CM. Proteoglycans in Mechanobiology of Tissues and Organs: Normal Functions and Mechanopathology. Proteoglycan Res 2024 Apr-Jun;2(2).
- Liu Y, Sun L, Li Y, Holmes C. Mesenchymal stromal/stem cell tissue source and in vitro expansion impact extracellular vesicle protein and miRNA compositions as well as angiogenic and immunomodulatory capacities. J Extracell Vesicles 2024 Aug;13(8):e12472.
- Hammer FA, Hölmich P, Nehlin JO, Vomstein K, Blønd L, Hölmich LR, Barfod KW, Bagge J. Microfragmented abdominal adipose tissue-derived stem cells from knee osteoarthritis patients aged 29-65 years demonstrate in vitro stemness and low levels of cellular senescence. J Exp Orthop 2024 Jul;11(3):e12056.
- Ferreira-Baptista C, Ferreira R, Fernandes MH, Gomes PS, Colaço B. Influence of the Anatomical Site on Adipose Tissue-Derived Stromal Cells' Biological Profile and Osteogenic Potential in Companion Animals. Vet Sci 2023 Nov 24;10(12).
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