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- Title
Scalable Enrichment of Immunomodulatory Human Acute Myeloid Leukemia Cell Line-Derived Extracellular Vesicles.
- Authors
Binder, Heide-Marie; Maeding, Nicole; Wolf, Martin; Cronemberger Andrade, André; Vari, Balazs; Krisch, Linda; Gomes, Fausto Gueths; Blöchl, Constantin; Muigg, Katharina; Poupardin, Rodolphe; Raninger, Anna M.; Heuser, Thomas; Obermayer, Astrid; Ebner-Peking, Patricia; Pleyer, Lisa; Greil, Richard; Huber, Christian G.; Schallmoser, Katharina; Strunk, Dirk
- Abstract
Acute myeloid leukemia (AML) cells can secrete trophic factors, including extracellular vesicles (EVs), instructing the stromal leukemic niche. Here, we introduce a scalable workflow for purification of immunomodulatory AML-EVs to compare their phenotype and function to the parental AML cells and their secreted soluble factors. AML cell lines HL-60, KG-1, OCI-AML3, and MOLM-14 released EVs with a peak diameter of approximately 80 nm in serum-free particle-reduced medium. We enriched EVs >100x using tangential flow filtration (TFF) and separated AML-derived soluble factors and cells in parallel. EVs were characterized by electron microscopy, immunoblotting, and flow cytometry, confirming the double-membrane morphology, purity and identity. AML-EVs showed significant enrichment of immune response and leukemia-related pathways in tandem mass-tag proteomics and a significant dose-dependent inhibition of T cell proliferation, which was not observed with AML cells or their soluble factors. Furthermore, AML-EVs dose-dependently reduced NK cell lysis of third-party K-562 leukemia targets. This emphasizes the peculiar role of AML-EVs in leukemia immune escape and indicates novel EV-based targets for therapeutic interventions.
- Subjects
ACUTE myeloid leukemia; VESICLES (Cytology); EXTRACELLULAR vesicles; MYELOID cells; LYSIS; KILLER cells
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 12, p3321
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10123321