3155 - Injectable Adipose-Derived Mesenchymal Stem Cell Exosome-Hydrogel System for Enhancing Radiosensitivity in Hepatocellular Carcinoma: Mechanisms and Effects
Presenter(s)
L. Wu, J. Yang, K. Jiang, and S. Yan; Department of Radiation Oncology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Purpose/Objective(s): To develop an injectable adipose-derived mesenchymal stem cell exosome (ASCEXOs)-hydrogel system for enhancing radiosensitivity in hepatocellular carcinoma (HCC) and to investigate its underlying mechanisms.
Materials/Methods: ASCEXOs were isolated and characterized using transmission electron microscopy and Western blot. An injectable hydrogel system was developed using natural polymers and loaded with ASCEXOs via microfluidic technology. The ASCEXOs-hydrogel system was characterized by infrared spectroscopy and spectrometry. In vitro and in vivo studies were conducted to evaluate the system's effects on HCC radiosensitivity. High-throughput sequencing and RT-PCR were used to identify and validate key microRNAs in ASCEXOs. The system's imaging capabilities and biosafety were assessed in animal models.
Results: The ASCEXOs-hydrogel system demonstrated sustained exosome release and enhanced retention in tumor tissues. It significantly increased radiosensitivity of HCC cells in vitro and improved tumor control in mouse xenograft models when combined with radiotherapy. MiRNA-127 was identified as highly enriched in ASCEXOs. The hydrogel component provided contrast enhancement for image-guided radiotherapy. No significant toxicity was observed in animal studies.
Conclusion: This novel ASCEXOs-hydrogel system shows promise in enhancing HCC radiosensitivity while enabling image guidance. It represents a potential strategy to improve radiotherapy outcomes for HCC patients. Further studies are warranted to elucidate the exact mechanisms and optimize the system for clinical translation.