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Binder HM, Maeding N, Wolf M, et al. Scalable Enrichment of Immunomodulatory Human Acute Myeloid Leukemia Cell Line-Derived Extracellular Vesicles. Cells. 2021;10(12)doi: 10.3390/cells10123321.
Binder, H. M., Maeding, N., Wolf, M., Cronemberger Andrade, A., Vari, B., Krisch, L., Gomes, F. G., Blöchl, C., Muigg, K., Poupardin, R., Raninger, A. M., Heuser, T., Obermayer, A., Ebner-Peking, P., Pleyer, L., Greil, R., Huber, C. G., Schallmoser, K., & Strunk, D. (2021). Scalable Enrichment of Immunomodulatory Human Acute Myeloid Leukemia Cell Line-Derived Extracellular Vesicles. Cells, 10(12), . https://doi.org/10.3390/cells10123321
Binder, Heide-Marie, et al. "Scalable Enrichment of Immunomodulatory Human Acute Myeloid Leukemia Cell Line-Derived Extracellular Vesicles." Cells vol. 10,12 (2021). doi: https://doi.org/10.3390/cells10123321
Binder HM, Maeding N, Wolf M, Cronemberger Andrade A, Vari B, Krisch L, Gomes FG, Blöchl C, Muigg K, Poupardin R, Raninger AM, Heuser T, Obermayer A, Ebner-Peking P, Pleyer L, Greil R, Huber CG, Schallmoser K, Strunk D. Scalable Enrichment of Immunomodulatory Human Acute Myeloid Leukemia Cell Line-Derived Extracellular Vesicles. Cells. 2021 Nov 26;10(12). doi: 10.3390/cells10123321. PMID: 34943829.
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Cells. 2021 Nov 26;10(12). doi: 10.3390/cells10123321.

Scalable Enrichment of Immunomodulatory Human Acute Myeloid Leukemia Cell Line-Derived Extracellular Vesicles.

Cells

Heide-Marie Binder, Nicole Maeding, Martin Wolf, André Cronemberger Andrade, Balazs Vari, Linda Krisch, Fausto Gueths Gomes, Constantin Blöchl, Katharina Muigg, Rodolphe Poupardin, Anna M Raninger, Thomas Heuser, Astrid Obermayer, Patricia Ebner-Peking, Lisa Pleyer, Richard Greil, Christian G Huber, Katharina Schallmoser, Dirk Strunk

Affiliations

  1. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
  2. Department of Transfusion Medicine and SCI-TReCS, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
  3. Department of Biosciences, Paris Lodron University, 5020 Salzburg, Austria.
  4. Vienna BioCenter Core Facilities GmbH, 1030 Vienna, Austria.
  5. 3rd Medical Department with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University, 5020 Salzburg, Austria.
  6. Salzburg Cancer Research Institute (SCRI) Center for Clinical Cancer and Immunology Trials (CCCIT) and Cancer Cluster Salzburg (CCS), 5020 Salzburg, Austria.
  7. Austrian Group for Medical Tumor Therapy (AGMT) Study Group, 1180 Vienna, Austria.

PMID: 34943829 DOI: 10.3390/cells10123321

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.

Keywords: MISEV; acute myeloid leukemia (AML); extracellular vesicles (EV); immunomodulation

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