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Blebbisomes are large, organelle-rich extracellular vesicles with cell-like properties

  • bgtaylor1
  • Nov 4, 2025
  • 2 min read

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Date:

March 2025

PMID:

Category:

N/A

Authors:

Dennis K Jeppesen, Zachary C Sanchez, Noah M Kelley, James B Hayes, Jessica Ambroise, Emma N Koory, Evan Krystofiak, Nilay Taneja, Qin Zhang, Matthew M Dungan, Olivia L Perkins, Matthew J Tyska, Ela W Knapik, Kevin M Dean, Amanda C Doran, Robert J Coffey, Dylan T Burnette

Abstract:

39984653


Cells secrete a large variety of extracellular vesicles (EVs) to engage in cell-to-cell and cell-to-environment intercellular communication. EVs are functionally involved in many physiological and pathological processes by interacting with cells that facilitate transfer of proteins, lipids and genetic information. However, our knowledge of EVs is incomplete. Here we show that cells actively release exceptionally large (up to 20 µm) membrane-enclosed vesicles that exhibit active blebbing behavior, and we, therefore, have termed them blebbisomes. Blebbisomes contain an array of cellular organelles that include functional mitochondria and multivesicular endosomes, yet lack a definable nucleus. We show that blebbisomes can both secrete and internalize exosomes and microvesicles. Blebbisomes are released from normal and cancer cells, can be observed by direct imaging of cancer cells in vivo and are present in normal bone marrow. We demonstrate that cancer-derived blebbisomes contain a plethora of inhibitory immune checkpoint proteins, including PD-L1, PD-L2, B7-H3, VISTA, PVR and HLA-E. These data identify a very large, organelle-containing functional EV that act as cell-autonomous mobile communication centres capable of integrating and responding to signals in the extracellular environment.


Acknowledgements:

The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, or the National Institute of Health.


The Translational and Basic Science Research in Early Lesions (TBEL) Research Consortia is supported and funded by grants from the National Cancer Institute and the National Institutes of Health under the following award numbers:


Project Number:

Awardee Organization

U54CA274374

Fred Hutchinson Cancer Center

U54CA274375

Houston Methodist Research Institute

U54CA274370

Johns Hopkins University

U54CA274371

UT MD Anderson Cancer Center

U54CA274367

Vanderbilt University Medical Center


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