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

Taguchi et al., 2019

Elita Genetics 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.