Exploring the Mechanisms Regulating Toroid Formation by Adipose-Derived Stem Cells Cultured on 3D Collagen Hydrogels
Dr. Matthew Stern
College of Arts and Sciences
Department of Biology
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Mesenchymal stem cells (MSCs) are a huge topic of interest to many researchers due to their therapeutic potential. MSCs can be harvested from various body tissues, including bone marrow, blood, and adipose tissue. Adipose-derived mesenchymal stem cells (ADSCs) are of particular therapeutic interest due to their great abundance and ease of accessibility relative to other types of MSCs. We have observed that ADSCs will migrate and self-organize into a toroid when applied to the top of a 3D type I collagen hydrogel. ADSCs fail to form toroids when embedded within collagen hydrogels, which raises the question of what specific environmental factors and cellular mechanisms regulate toroid formation? The binding of the ligand CXCL12 to the chemokine receptor CXCR4 initiates chemotactic signals in ADSCs. The goal of this study is to determine if the CXCL12:CXCR4 signaling axis is essential to the migration and self-organization required for ADSCs to achieve toroid formation. We hypothesized that the binding of the ligand CXCL12 to the chemokine receptor CXCR4 is essential for toroid formation by the telomerase immortalized human ADSCs used in our culture model. The selective inhibitor AMD3100 can be used to block the interaction between CXCR4 and CXCL12. To test our hypothesis, we compared toroid formation by ADSCs cultured in two concentrations of AMD3100 to control conditions. We used phase-contrast microscopy to qualitatively monitor toroid formation and integrated software to measure the geometry of any structures formed 24 hours after plating. We found that there was no observable effect caused by the inhibitor. These results suggest that the CXCL12:CXCR4 signaling axis is not essential for toroid formation under the conditions tested. Future directions include testing different numbers and sources of ADSCs in our system and using selective inhibitors of downstream pathways known to be important for cellular migration and self-organization.
Cobb, Mary-Catherine, "Exploring the Mechanisms Regulating Toroid Formation by Adipose-Derived Stem Cells Cultured on 3D Collagen Hydrogels" (2020). S.U.R.E Posters. 11.
South Carolina EPSCoR/IDeA GEAR Collaborative Research Program
South Carolina INBRE (NIH-NIGMS P20GM103499)