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.
|Original language||English (US)|
|Journal||ACS Biomaterials Science & Engineering|
|State||Published - Nov 21 2021|
Bibliographical noteKAUST Repository Item: Exported on 2021-11-24
Acknowledged KAUST grant number(s): OSR-2018-CRG7-3709
Acknowledgements: We wish to acknowledge Zixuan Henry Lu for his assistance with the electrical measurements, Achilleas Savva for his assistance with the EEC modeling, and Anil Koklu for his assistance in MAE design and fabrication. This work was supported by the National Science Foundation Graduate Research Fellowship (grant number DGE-1650441), the Sloan Foundation (grant number 70481) to J.U., and 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. This work was performed in part at the Cornell NanoScale Facility, an NNCI member supported by the NSF grant NNCI-2025233. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of any of the funding institutions.