Pretreating Mesenchymal Stem Cells with Cancer Conditioned‐Media or Proinflammatory Cytokines Changes the Tumor and Immune Targeting by Nanoghosts Derived from these Cells

Pretreating Mesenchymal Stem Cells with Cancer Conditioned‐Media or Proinflammatory Cytokines Changes the Tumor and Immune Targeting by Nanoghosts Derived from these Cells

Nanoghosts (NGs) are nanovesicles reconstructed from the cytoplasmic membranes of mesenchymal stem cells (MSCs). By retaining MSC membranes, the NGs retain the ability of these cells to home in on multiple tumors, laying the foundations, thereby, for the development of a targeted drug delivery platf...

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Bibliographic Details
Published in:Advanced healthcare materials Vol. 8; no. 10; pp. e1801589 - n/a
Main Authors: Lupu‐Haber, Yael, Bronshtein, Tomer, Shalom‐Luxenburg, Hagit, D'Atri, Domenico, Oieni, Jacopo, Kaneti, Limor, Shagan, Alona, Hamias, Shani, Amram, Liat, Kaneti, Galoz, Cohen Anavy, Noa, Machluf, Marcelle
Format: Journal Article
Language:English
Published: Germany Wiley Subscription Services, Inc 01-05-2019
Subjects:
Cancer
conditioned‐media
Conditioning
Cytokines
Cytoplasmic membranes
Drug delivery
Drug delivery systems
Endothelial cells
Immune system
Inflammation
Membrane proteins
Membranes
Mesenchymal stem cells
Mesenchyme
nanoghosts
nanovesicles
Protein composition
Stem cells
Tumor necrosis factor
Tumors
conditioned-media
cytokines
nanoghosts
drug delivery
nanovesicles
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Summary:Nanoghosts (NGs) are nanovesicles reconstructed from the cytoplasmic membranes of mesenchymal stem cells (MSCs). By retaining MSC membranes, the NGs retain the ability of these cells to home in on multiple tumors, laying the foundations, thereby, for the development of a targeted drug delivery platform. The susceptibility of MSCs to functional changes, following their exposure to cytokines or cancer‐derived conditioned‐media (CM), presents the opportunity to modify the NGs by conditioning their source cells. This opportunity is investigated by comparing the membrane protein composition and the tumor uptake of NGs derived from naïve MSCs (N‐NG) against conditioned NGs made from MSCs pre‐treated with conditioned‐media (CM‐NG) or with a mix of the proinflammatory cytokines TNF‐α and IL‐1β (Cyto‐NG). CM‐NGs are found to be more targeted towards immune cells than Cyto‐ or N‐NGs, while Cyto‐NGs are the most tumor‐targeted ones, with similar immune‐targeting capacity as N‐NGs but with a higher affinity towards endothelial cells. Proteomic variations were wider in the CM‐NGs, with exceptionally higher levels of ICAM‐1 compared to N‐ and Cyto‐NGs. From a translational point of view, the data show that the tumor‐targeting ability of the NGs, and possibly that of other MSC‐derived extracellular vesicles, can be enhanced by simple conditioning of their source cells. Wide variations are detected in the in vitro and in vivo fate and the proteomic composition between naïve nanoghosts (N‐NGs, as seen in the background), media‐conditioned nanoghosts (CM‐NG), and cytokine‐conditioned nanoghosts (Cyto‐NG) that are produced from naïve mesenchymal stem cells (MSCs), MSCs conditioned with media from cancer cells, or MSC pretreated with TNF‐alpha and IL1‐beta, respectively.
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ISSN:2192-2640
2192-2659
DOI:10.1002/adhm.201801589