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MSC in Tendon and Joint Disease: The Context-Sensitive Link Between Targets and Therapeutic Mechanisms
Susanne Pauline Roth1, Janina Burk2, Walter Brehm1
1Veterinary Teaching Hospital, Department for Horses, Veterinary Faculty, University of Leipzig, Leipzig, Germany.
Abstract:
Mesenchymal stromal cells (MSC) represent a promising treatment option for tendon disorders and joint diseases, primarily osteoarthritis. Since MSC are highly context-sensitive to their microenvironment, their therapeutic efficacy is influenced by their tissue-specific pathologically altered targets. These include not only cellular components, such as resident cells and invading immunocompetent cells, but also components of the tissue-characteristic extracellular matrix. Although numerous in vitro models have already shown potential MSC-related mechanisms of action in tendon and joint diseases, only a limited number reflect the disease-specific microenvironment and allow conclusions about well-directed MSC-based therapies for injured tendon and joint-associated tissues. In both injured tissue types, inflammatory processes play a pivotal pathophysiological role. In this context, MSC-mediated macrophage modulation seems to be an important mode of action across these tissues. Additional target cells of MSC applied in tendon and joint disorders include tenocytes, synoviocytes as well as other invading and resident immune cells. It remains of critical importance whether the context-sensitive interplay between MSC and tissue- and disease-specific targets results in an overall promotion or inhibition of the desired therapeutic effects. This review presents the authors' viewpoint on disease-related targets of MSC therapeutically applied in tendon and joint diseases, focusing on the equine patient as valid animal model.
Insights
Mesenchymal stromal cells (MSC) show therapeutic potential for tendon and joint diseases by modulating the microenvironment. Understanding MSC interactions with specific cellular and matrix targets is crucial for effective equine therapies.
Area of Science:
- Veterinary Medicine
- Regenerative Medicine
- Cell Biology
Background:
- Mesenchymal stromal cells (MSC) are investigated for treating tendon and joint disorders like osteoarthritis.
- MSC efficacy depends on their interaction with the pathologically altered microenvironment, including resident and immune cells, and the extracellular matrix.
- Existing in vitro models often fail to fully replicate disease-specific microenvironments for tendon and joint tissues.
Purpose of the Study:
- To review disease-related targets of MSC in equine tendon and joint diseases.
- To highlight the importance of the tissue-specific microenvironment in MSC therapeutic efficacy.
- To discuss MSC-mediated macrophage modulation as a key mechanism.
Main Methods:
- Review of existing literature on MSC mechanisms in tendon and joint diseases.
- Focus on cellular targets (tenocytes, synoviocytes, immune cells) and extracellular matrix components.
- Consideration of the equine patient as a model for these conditions.
Main Results:
- MSC therapeutic effects are context-sensitive, influenced by interactions with specific cellular and matrix targets.
- Macrophage modulation by MSC is a significant mechanism of action in inflammatory joint and tendon conditions.
- The interplay between MSC and disease-specific targets can either promote or inhibit therapeutic outcomes.
Conclusions:
- Further research is needed to elucidate the complex interactions between MSC and their targets in specific disease contexts.
- Optimizing MSC-based therapies requires a deep understanding of the microenvironmental influences.
- The equine model offers valuable insights into MSC applications for tendon and joint pathologies.
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