SYSTEMIC IMMUNOMODULATION OF MYELOID-DERIVED SUPPRESSOR CELLS IN A MODEL OF MUSCULOSKELETAL TRAUMA USING ALL-TRANS RETINOIC ACID
| dc.contributor.advisor | Guldberg, Bob | |
| dc.contributor.advisor | Guyer, Tyler | |
| dc.contributor.advisor | Munger, Lisa | |
| dc.contributor.author | Gill, Dylan | |
| dc.date.accessioned | 2024-09-20T18:53:10Z | |
| dc.date.available | 2024-09-20T18:53:10Z | |
| dc.date.issued | 2024-05 | |
| dc.description | 38 pages | |
| dc.description.abstract | Musculoskeletal trauma remains a significant challenge clinically, often leading to complications such as bone nonunion, infection, prolonged hospitalization, high treatment costs, and potential disabilities. The current standard treatment, autologous bone grafting, has limitations including donor site morbidity and limited bone availability, necessitating exploration of alternative approaches. Immune responses play a critical role in musculoskeletal healing, with distinct phases of inflammation and regenerative/anti-inflammatory processes. The transition from M1 to M2 macrophages is crucial for soft and hard callus formation during bone healing. However, dysregulated immune responses, characterized by prolonged elevation of pro- and anti-inflammatory mediators, can hinder healing and tissue repair. Recent research has focused on systemic immune responses following trauma, highlighting the balance between circulating pro-inflammatory and anti-inflammatory markers to prevent tissue damage and promote healing. Immune suppressor cells like myeloid-derived suppressor cells (MDSCs) play a pivotal role in immune dysregulation post-trauma and may be a factor in poor healing. Targeting MDSCs presents a complex challenge due partly to their heterogeneity, necessitating innovative therapeutic strategies. Here, we tested several treatment methods for MDSC depletion previously developed for use in cancer models to examine their effects on MDSCs in vitro in blood sourced from a trauma model. All-Trans Retinoic Acid (ATRA) in particular showed promise in modulating MDSCs initially in vitro and in subsequent in vivo experiments. ATRA is also known to have effects on bone growth and may alter osteoclastogenesis, giving it further potential as a novel therapeutic intervention in musculoskeletal trauma. Further research into the intricate interplay of immune responses following trauma and particularly therapeutic modulation of aberrant cells such as MDSCs is essential for advancing treatment strategies and improving outcomes in musculoskeletal trauma patients. | |
| dc.identifier.uri | https://hdl.handle.net/1794/30085 | |
| dc.language.iso | en_US | |
| dc.publisher | University of Oregon | |
| dc.subject | immunomodulation | |
| dc.subject | myeloid derived suppressor cells | |
| dc.subject | all-trans retinoic acid | |
| dc.subject | musculoskeletal | |
| dc.subject | immunotherapeutics | |
| dc.title | SYSTEMIC IMMUNOMODULATION OF MYELOID-DERIVED SUPPRESSOR CELLS IN A MODEL OF MUSCULOSKELETAL TRAUMA USING ALL-TRANS RETINOIC ACID | |
| dc.type | Thesis |