3D culturing as a promising strategy to enhance the angiogenic potential of adipose stem cell-derived secretome: insights into the role of miR-145-5p/ANGPT2 axis DOI Creative Commons
Giulia Gerini, Emanuela Mari, Paola Pontecorvi

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 28, 2025

Adipose-derived mesenchymal stem cells (ASCs) represent a valid therapeutic option for clinical application in several diseases, mostly due to the paracrine activity of their secretome, exerting pro-angiogenic, antinflammatory and immunosuppressive effects. Recently, 3D culturing models has been shown significantly influence intrinsic characteristics these cells, gene expression secretome's composition, thus affecting ASC effects potential. This study aims investigate feasibility exploiting as tool improve secretome efficacy. ASCs were cultured monolayers via conventional two-dimensional (2D) methods or induced form spheroids by seeding them on 96-well ultra-low attachment (ULA) plates. The phenotypical characterization 3D-ASCs was performed through immunofluorescence analyses. composition angiogenic potential 3D-ASC-derived assessed means protein array functional tube formation assay, respectively. We analyzed profile 92 angiogenesis-related genes 2D versus cultures qRT-PCR array, GO term enrichment analysis followed network applied identify top hub genes. specific angiomiRs qRT-PCR. role miR-145-5p investigated transfection with mimics/anti-miR. showed increased stemness, cell-cell cell-ECM interactions respect 2D-cultured cells. secretion cytokines involved promotion angiogenesis, resulting improved HUVEC Mechanistically, data indicated downregulation angiopoietin-2 (ANGPT2) key factor 3D-ASC-secretome-induced angiogenesis. In addition, ANGPT2 recognized predicted target miR-145-5p, one found upregulated 3D-ASCs. Depletion altered All findings corroborate our hypothesis that is able positively modulate terms pro-angiogenic Indeed, contributes shed light miR-145-5p/ANGPT2 axis this process, opening way innovative potentiation strategies implement secretome-based therapies, broad applications.

Language: Английский

3D culturing as a promising strategy to enhance the angiogenic potential of adipose stem cell-derived secretome: insights into the role of miR-145-5p/ANGPT2 axis DOI Creative Commons
Giulia Gerini, Emanuela Mari, Paola Pontecorvi

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 28, 2025

Adipose-derived mesenchymal stem cells (ASCs) represent a valid therapeutic option for clinical application in several diseases, mostly due to the paracrine activity of their secretome, exerting pro-angiogenic, antinflammatory and immunosuppressive effects. Recently, 3D culturing models has been shown significantly influence intrinsic characteristics these cells, gene expression secretome's composition, thus affecting ASC effects potential. This study aims investigate feasibility exploiting as tool improve secretome efficacy. ASCs were cultured monolayers via conventional two-dimensional (2D) methods or induced form spheroids by seeding them on 96-well ultra-low attachment (ULA) plates. The phenotypical characterization 3D-ASCs was performed through immunofluorescence analyses. composition angiogenic potential 3D-ASC-derived assessed means protein array functional tube formation assay, respectively. We analyzed profile 92 angiogenesis-related genes 2D versus cultures qRT-PCR array, GO term enrichment analysis followed network applied identify top hub genes. specific angiomiRs qRT-PCR. role miR-145-5p investigated transfection with mimics/anti-miR. showed increased stemness, cell-cell cell-ECM interactions respect 2D-cultured cells. secretion cytokines involved promotion angiogenesis, resulting improved HUVEC Mechanistically, data indicated downregulation angiopoietin-2 (ANGPT2) key factor 3D-ASC-secretome-induced angiogenesis. In addition, ANGPT2 recognized predicted target miR-145-5p, one found upregulated 3D-ASCs. Depletion altered All findings corroborate our hypothesis that is able positively modulate terms pro-angiogenic Indeed, contributes shed light miR-145-5p/ANGPT2 axis this process, opening way innovative potentiation strategies implement secretome-based therapies, broad applications.

Language: Английский

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