The cellular response to extracellular vesicles is dependent on their cell source and dose.

Autor: Hagey DW; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden., Ojansivu M; Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden., Bostancioglu BR; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden., Saher O; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden.; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt., Bost JP; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden., Gustafsson MO; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden., Gramignoli R; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden., Svahn M; NextCell Pharma AB, Stockholm, Sweden., Gupta D; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden.; Department of Paediatrics, University of Oxford, Oxford OX3 7TY, UK., Stevens MM; Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.; Department of Materials, Department of Bioengineering, Institute of Biomedical Engineering, Imperial College London, London, UK., Görgens A; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden.; Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., El Andaloussi S; Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.; Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Sep; Vol. 9 (35), pp. eadh1168. Date of Electronic Publication: 2023 Sep 01.
DOI: 10.1126/sciadv.adh1168
Abstrakt: Extracellular vesicles (EVs) have been established to play important roles in cell-cell communication and shown promise as therapeutic agents. However, we still lack a basic understanding of how cells respond upon exposure to EVs from different cell sources at various doses. Thus, we treated fibroblasts with EVs from 12 different cell sources at doses between 20 and 200,000 per cell, analyzed their transcriptional effects, and functionally confirmed the findings in various cell types in vitro, and in vivo using single-cell RNA sequencing. Unbiased global analysis revealed EV dose to have a more significant effect than cell source, such that high doses down-regulated exocytosis and up-regulated lysosomal activity. However, EV cell source-specific responses were observed at low doses, and these reflected the activities of the EV's source cells. Last, we assessed EV-derived transcript abundance and found that immune cell-derived EVs were most associated with recipient cells. Together, this study provides important insights into the cellular response to EVs.
Databáze: MEDLINE