Pretreating Mesenchymal Stem Cells with Cancer Conditioned‐Media or Proinflammatory Cytokines Changes the Tumor and Immune Targeting by Nanoghosts Derived from these Cells. Issue 10 (9th April 2019)

• Record Type: Journal Article
• 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
• Is Part Of: Advanced healthcare materials. Volume 8:Issue 10(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-04-09
• Subjects: conditioned‐media -- cytokines -- drug delivery -- nanoghosts -- nanovesicles; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201801589
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: 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. Abstract : 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.