Influence of Donor's Age on Immunomodulatory Properties of Canine Adipose Tissue-Derived Mesenchymal Stem Cells

Elita Summary
As stem cell therapies gain traction in veterinary practice, understanding the biological characteristics of the cells we work with becomes increasingly important, particularly in the context of autologous use.
This 2019 study by Taguchi et al. explored a specific and clinically relevant question: Does donor age affect the immunomodulatory function of adipose-derived mesenchymal stem cells (AD-MSCs) in dogs? The short answer is yes, and the implications are important for how and when we consider stem cell collection and use.
Study Design at a Glance
- Groups: AD-MSCs were harvested from young (≤3 years) and old (≥8 years) healthy dogs.
- Focus: The team assessed the MSCs’ ability to suppress lymphocyte proliferation and evaluated the expression of key immunomodulatory genes.
- Assays: Co-culture assays with stimulated lymphocytes were used to measure immunosuppressive function, alongside qPCR for gene expression analysis (e.g., IDO, IL-6, HGF, and TGF-β).
Key Findings
- Reduced immunosuppression in older donors: AD-MSCs from aged dogs showed significantly lower suppression of lymphocyte proliferation than those from young donors.
- Altered gene expression: MSCs from older dogs exhibited lower expression of key immunomodulatory genes, including IDO and HGF, which are known to modulate immune responses and inflammation.
- Reduced response to inflammatory stimuli: When exposed to pro-inflammatory cytokines (IFN-γ and TNF-α), MSCs from older dogs showed a weaker upregulation of immunomodulatory genes, suggesting impaired responsiveness to inflammatory environments.
- Although the AD-MSCs from younger dogs had higher activated T cell suppression ability, the levels of secreted PGE2 and IDO were not different compared to older dogs. However, study size of N=18 is likely not enough to see a difference between the two groups (see error bars in Figure 5).
Why This Matters Clinically
- Autologous therapy may be less effective in aged dogs: The findings suggest that even if MSCs can be successfully harvested and expanded from older dogs, their functional potency, especially in modulating immune or inflammatory responses, may be diminished.
- Supports early collection: Younger donor cells appear to have a broader and more adaptable immunomodulatory profile, making a strong case for early banking of stem cells, particularly in breeds predisposed to chronic inflammatory or degenerative conditions.
- Potential relevance for autoimmune and inflammatory use cases: In indications where immune modulation is key (e.g., immune-mediated arthritis or IBD), donor age may have even greater implications for treatment outcomes.
Limitations and Considerations
- In vitro data: While compelling, the study is bench-based. Clinical correlation (i.e. in vivo immunomodulatory efficacy) remains to be established.
- Sample size: A relatively small number of donors were used, though the experimental design was rigorous and reproducible.
- Focus on adipose MSCs only: While relevant to veterinary practice, similar studies on bone marrow or other cell sources would be valuable for broader context.
Implications for Elita
This study reinforces our internal research direction and product strategy. We're actively working to ensure that the cells we bank are collected at a time when they’re at their functional best, not just viable, but potent. As we continue evaluating cell composition and responsiveness, age-related metrics will remain a core part of our approach to quality and long-term clinical utility.