Dual Mode Sensing of Binding and Blocking of Cancer Exosomes to Biomimetic Human Primary Stem Cell Surfaces.
Authors
Traberg, Walther C
Hama, Adel
Druet, Victor
Ooi, Amanda
Huerta, Miriam
Publication Date
2021-12-13Journal Title
ACS Biomater Sci Eng
ISSN
2373-9878
Publisher
American Chemical Society (ACS)
Number
acsbiomaterials.1c01056
Language
en
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Uribe, J., Traberg, W. C., Hama, A., Druet, V., Mohamed, Z., Ooi, A., Pappa, A., et al. (2021). Dual Mode Sensing of Binding and Blocking of Cancer Exosomes to Biomimetic Human Primary Stem Cell Surfaces.. ACS Biomater Sci Eng, (acsbiomaterials.1c01056) https://doi.org/10.1021/acsbiomaterials.1c01056
Abstract
Cancer-derived exosomes (cEXOs) facilitate transfer of information between tumor and human primary stromal cells, favoring cancer progression. Although the mechanisms used during this information exchange are still not completely understood, it is known that binding is the initial contact established between cEXOs and cells. Hence, studying binding and finding strategies to block it are of great therapeutic value. However, such studies are challenging for a variety of reasons, including the need for human primary cell culture, the difficulty in decoupling and isolating binding from internalization and cargo delivery, and the lack of techniques to detect these specific interactions. In this work, we created a supported biomimetic stem cell membrane incorporating membrane components from human primary adipose-derived stem cells (ADSCs). We formed the supported membrane on glass and on multielectrode arrays to offer the dual option of optical or electrical detection of cEXO binding to the membrane surface. Using our platform, we show that cEXOs bind to the stem cell membrane and that binding is blocked when an antibody to integrin β1, a component of ADSC surface, is exposed to the membrane surface prior to cEXOs. To test the biological outcome of blocking this interaction, we first confirm that adding cEXOs to cultured ADSCs leads to the upregulation of vascular endothelial growth factor, a measure of proangiogenic activity. Next, when ADSCs are first blocked with anti-integrin β1 and then exposed to cEXOs, the upregulation of proangiogenic activity and cell proliferation are significantly reduced. This biomimetic membrane platform is the first cell-free label-free in vitro platform for the recapitulation and study of cEXO binding to human primary stem cells with potential for therapeutic molecule screening as it is compatible with scale-up and multiplexing.
Sponsorship
a research grant
from King Abdullah University of Science and Technology
under contract OSR-2018-CRG7-3709 to S.I., R.M.O, and S.D.
W.T. acknowledges funding from the Cambridge Trust.
Funder references
King Abdullah University of Science and Technology (KAUST) (OSR-2018-CRG7-3709)
Embargo Lift Date
2022-11-21
Identifiers
External DOI: https://doi.org/10.1021/acsbiomaterials.1c01056
This record's URL: https://www.repository.cam.ac.uk/handle/1810/331076
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