Adipose-Derived Mesenchymal Stromal Cells Co-Cultured with Primary Mixed Glia to Reduce Prion-Induced Inflammation
August 11th, 2023
Adipose-derived mesenchymal stromal cells (AdMSCs) have potent immunomodulatory properties useful for treating diseases associated with inflammation. We demonstrate how to isolate and culture murine AdMSCs and primary mixed glia, stimulate AdMSCs to upregulate anti-inflammatory genes and growth factors, assess migration of AdMSCs, and co-culture AdMSCs with primary mixed prion-infected glia.
Our work focuses on prion diseases, which are fatal neurodegenerative diseases caused by the misfolding of the prion protein in the brain. Few studies have focused on the impact of glial cells on neuronal death. We want to understand if halting inflammation caused by glial cells can be a therapeutic approach.
There has been a recent discovery in the mesenchymal stromal cell field, revealing that the protective properties stem from the extracellular vesicles they release. We aim to delve deeper into the contents of these vesicles and understand how they provide protection against prion-induced glial inflammation. Currently in the field of neurodegeneration, there are a few avenues that are successful at halting neuroinflammation.
These include small molecules and genetic modulation using adeno or lentiviruses. However, none have been able to fully reduce inflammation, specifically in large areas of the brain. The most significant finding that we have been able to establish is that through cell therapy, we are able to slow prion-disease progression through inhibition of glial inflammation.
The use of a combined with the primary glial-cell model of disease will allow us to continue to ask about cellular stress pathways important in neuroprotection, in a more efficient and direct matter than the use of solely in-vivo models.
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Overview
This study investigates the therapeutic potential of adipose-derived mesenchymal stromal cells (AdMSCs) for prion diseases, focusing on their immunomodulatory effects and the role of glial inflammation in neurodegeneration. By isolating, culturing, and co-culturing murine AdMSCs with primary mixed glial cells, the research aims to explore mechanisms behind inflammation and neuroprotection.
Key Study Components
Area of Science
- Neurodegenerative Diseases
- Immunomodulation
- Cell Therapy
Background
- Prion diseases are fatal neurodegenerative disorders caused by misfolded proteins.
- Inflammation from glial cells contributes to neuronal death.
- Current therapies have not fully addressed neuroinflammation effectively.
- AdMSCs have shown promise due to their capacity for releasing protective extracellular vesicles.
Purpose of Study
- To evaluate the potential of AdMSCs in modulating inflammation in prion diseases.
- To explore the effects of AdMSCs on glial cells and their protective mechanisms.
- To assess the efficacy of AdMSCs in slowing prion disease progression.
Methods Used
- Culture of adipose-derived mesenchymal stromal cells (AdMSCs) and primary mixed glia.
- No specific multiomics workflows were mentioned.
- Assessment of migration and co-culture with prion-infected glia were key steps.
- Stimulation of AdMSCs to upregulate anti-inflammatory genes was performed.
Main Results
- Demonstrated that AdMSCs can slow the progression of prion disease by inhibiting glial inflammation.
- Findings suggest that the protective effects are linked to the extracellular vesicles released by AdMSCs.
- Showed that halting inflammation could provide a new therapeutic approach for neuroprotection.
Conclusions
- This study highlights the role of AdMSCs in neuroprotection against prion diseases.
- The findings underscore the potential for using cell therapy to address glial inflammation.
- Implications are significant for understanding the mechanisms of neurodegeneration and potential therapeutic interventions.
