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. 2024 Jun 18;13(1):61.
doi: 10.1186/s40164-024-00526-2.

Reconstructed colorectal cancer model to dissect the anti-tumor effect of mesenchymal stromal cells derived extracellular vesicles

Edoardo D'Angelo  1   2 , Sarah Tassinari  3 , Andrea Biccari  4 , Sara Crotti  5 , Francesca Sensi  5   6 , Asia Marangio  4 , Ombretta Repetto  7 , Giuseppe Corona  7 , Linda Bellucci  8   9 , Federica Antico  3 , Federico Caicci  10 , Gaya Spolverato  4 , Giovanni Montini  8   9   11 , Benedetta Bussolati  3 , Marco Agostini #  4   5 , Federica Collino #  12   13   14
Affiliations

Reconstructed colorectal cancer model to dissect the anti-tumor effect of mesenchymal stromal cells derived extracellular vesicles

Edoardo D'Angelo et al. Exp Hematol Oncol. .
No abstract available

Keywords: 3D model; Colorectal cancer; Extracellular vesicles; Mesenchymal stromal cells.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
MSC-EVs active uptake in the 3D-CRC model and proteome analysis of DM and RM samples. (A) Representative immunofluorescence images of CRC biopsies repopulated with ZSGreen-HT29 CRC cell line incubated with EVs-DiL or PBS-DiL. Cell nuclei were counterstained using DAPI. Scale bar=20 μm (left panel). 3D reconstruction of EVs-DiL or PBS-DiL (red) diffusion in decellularized CRC biopsies repopulated with ZSGreen-HT29 CRC cell line (green, right panel; scale bar = 20 μm). (B) Schematic representation of proteome and secretome analysis in DM and RM samples in which differentially abundant proteins were investigated in DM (upper panel) or RM (lower panel) after EV-treatment or not. Matrix samples were divided into four groups: (i) decellularized CRC biopsies, EV-untreated (DM-CTRL) or (ii) EV-treated (DM-EV); (iii) decellularized CRC biopsies repopulated with HT29 cancer cell line, EV-untreated (RM-CTRL) or (iv) decellularized CRC biopsies repopulated with HT29 cancer cell line EV-treated (RM-EV). Supernatants (S) of each condition (labelled in red) were also collected. Volcano plots of the comparison between the proteomic profile of RM and DM after incubation with MSC-EVs (C) or control medium (D); up-regulated proteins (red squares) and down-regulated proteins (green squares) between RM-EV vs. DM-EV and RM-CTRL vs. DM-CTRL. Venn diagrams of exclusively up-regulated (E) or down-regulated (F) proteins in RM-CTRL and RM-EVs groups. Up-regulated proteins specific of CTRL group are labelled in blue, those specific of EVs treated-group are in red and the up-regulated proteins shared by the two groups are in dark red. Down-regulated proteins specific of CTRL group are labelled in pink, those specific of EVs treated-group are in yellow and the down-regulated proteins shared by the two groups are in orange. (G-H) Functional annotation of the respectively up-regulated proteins in RM-CTRL and RM-EV using DAVID Bioinformatics Resources for Biological processes
Fig. 2
Fig. 2
Biological effect on cell cycle and apoptosis of the MSC-EVs treatment in the 3D-CRC model and secretome analysis of RM samples. (A) Representative H&E images of 3D-CRC untreated (RM) or treated (RM-EV) with MSC-EVs (left panel). The apoptotic cells were detected using TUNEL assay, the DNA fragmentation is indicated by ApopTag Plus Peroxidase positive staining (brown) (right panel). Scale bar = 20 μm. (B) Quantification of apoptotic cells in the 3D-CRC model treated or untreated with MSC-EVs and expressed as apoptotic cells/field. Gene expression level of apoptosis and cell cycle-related genes in the 3D-CRC model treated or untreated with MSC-EVs: (C) BCL-2 and BAK1. (D) C-MYC, KI-67, CCND2, CCNE1 and CDKN1A. P< 0,05 vs. RM, unpaired two-sided Student’s t-test. (E) Volcano plots of the comparison between the secretome profile of RM-EV vs. RM-CTRL, The up-regulated proteins (red squares) and down-regulated proteins (green squares) in the RM-EV secretome in respect to the RM-CTRL were defined. The 23 secreted proteins up-regulated in RM-EV were functionally annotated using DAVID Bioinformatics Resources in (F) Biological processes, (G) Molecular functions and (H) Cellular components
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