Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age.
Authors: Bagge Jasmin, MacLeod James N, Berg Lise C
Journal: Frontiers in veterinary science
Summary
Mesenchymal stem cells (MSCs) harvested from bone marrow and adipose tissue are increasingly used in equine practice for autologous cell therapy, yet therapeutic protocols typically require 10–100 million cells, necessitating in vitro expansion—a process that may be compromised in older horses, as documented in human and rodent models. Bagge and colleagues examined proliferation capacity in both cell types across five age cohorts (newborn through geriatric; ≥22 years) using EdU incorporation assays and targeted mRNA analysis for proliferation, ageing, and senescence markers. Both BM- and AT-derived MSCs demonstrated significantly reduced cellular proliferation in the geriatric group compared with younger horses, with mRNA profiling revealing upregulation of tumour suppressors and apoptotic genes alongside downregulation of pro-cycling genes in cells from aged donors. The findings suggest that practitioners should approach autologous MSC therapy with particular caution in horses aged 18 years and older, as cell expansion may prove more challenging—potentially requiring longer culture periods or alternative sourcing strategies to meet therapeutic cell counts. Whilst this work establishes an important age-related threshold for MSC proliferation capacity in equines, further investigation into functional parameters relevant to clinical efficacy (differentiation potential, immunomodulatory activity, migration capacity) would strengthen recommendations for geriatric patients requiring regenerative therapy.
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Practical Takeaways
- •Autologous MSC therapy may be less effective in geriatric horses (≥22 years) due to reduced cell proliferation capacity, potentially requiring alternative sourcing or treatment approaches for older patients
- •MSC harvesting and expansion protocols should be optimized for horses over 18 years old, as standard cell expansion targets (10-100 million cells) may be difficult to achieve
- •Consider sourcing MSCs from younger donor horses or exploring alternative cell therapy options when treating older patients requiring cell-based therapy
Key Findings
- •Cellular proliferation of both bone marrow and adipose tissue-derived MSCs declined significantly in geriatric horses (≥22 years) compared to younger age groups
- •MSCs from horses aged below 18 years maintained high proliferation capacity in vitro
- •Geriatric MSCs showed upregulation of tumor suppressors and apoptotic genes with downregulation of pro-cycling genes, indicating cellular senescence
- •Bone marrow and adipose tissue MSCs were equally affected by donor age