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Tytuł pozycji:

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

Tytuł:
Scalable Enrichment of Immunomodulatory Human Acute Myeloid Leukemia Cell Line-Derived Extracellular Vesicles.
Autorzy:
Binder HM; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Maeding N; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Wolf M; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Cronemberger Andrade A; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Vari B; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Krisch L; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.; Department of Transfusion Medicine and SCI-TReCS, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Gomes FG; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Blöchl C; Department of Biosciences, Paris Lodron University, 5020 Salzburg, Austria.
Muigg K; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Poupardin R; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Raninger AM; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Heuser T; Vienna BioCenter Core Facilities GmbH, 1030 Vienna, Austria.
Obermayer A; Department of Biosciences, Paris Lodron University, 5020 Salzburg, Austria.
Ebner-Peking P; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Pleyer L; 3rd Medical Department with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University, 5020 Salzburg, Austria.; Salzburg Cancer Research Institute (SCRI) Center for Clinical Cancer and Immunology Trials (CCCIT) and Cancer Cluster Salzburg (CCS), 5020 Salzburg, Austria.; Austrian Group for Medical Tumor Therapy (AGMT) Study Group, 1180 Vienna, Austria.
Greil R; 3rd Medical Department with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University, 5020 Salzburg, Austria.; Salzburg Cancer Research Institute (SCRI) Center for Clinical Cancer and Immunology Trials (CCCIT) and Cancer Cluster Salzburg (CCS), 5020 Salzburg, Austria.; Austrian Group for Medical Tumor Therapy (AGMT) Study Group, 1180 Vienna, Austria.
Huber CG; Department of Biosciences, Paris Lodron University, 5020 Salzburg, Austria.
Schallmoser K; Department of Transfusion Medicine and SCI-TReCS, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Strunk D; Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Cell Therapy Institute, Paracelsus Medical University (PMU), 5020 Salzburg, Austria.
Źródło:
Cells [Cells] 2021 Nov 26; Vol. 10 (12). Date of Electronic Publication: 2021 Nov 26.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI
MeSH Terms:
Immunomodulation*
Extracellular Vesicles/*metabolism
Leukemia, Myeloid, Acute/*immunology
Cell Line, Tumor ; Cell Proliferation ; Extracellular Vesicles/ultrastructure ; Humans ; Immunosuppression Therapy ; Killer Cells, Natural/immunology ; T-Lymphocytes/immunology
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Contributed Indexing:
Keywords: MISEV; acute myeloid leukemia (AML); extracellular vesicles (EV); immunomodulation
Entry Date(s):
Date Created: 20211224 Date Completed: 20220120 Latest Revision: 20220120
Update Code:
20240105
PubMed Central ID:
PMC8699161
DOI:
10.3390/cells10123321
PMID:
34943829
Czasopismo naukowe
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.
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