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Review
. 2020 Nov;9(11):1310-1330.
doi: 10.1002/sctm.20-0161. Epub 2020 Jun 15.

Cross talk between mesenchymal and glioblastoma stem cells: Communication beyond controversies

Adriana Bajetto  1 , Stefano Thellung  1 , Irene Dellacasagrande  1 , Aldo Pagano  2   3 , Federica Barbieri  1 , Tullio Florio  1   3
Affiliations
Review

Cross talk between mesenchymal and glioblastoma stem cells: Communication beyond controversies

Adriana Bajetto et al. Stem Cells Transl Med. 2020 Nov.

Abstract

Mesenchymal stem cells (MSCs) can be isolated from bone marrow or other adult tissues (adipose tissue, dental pulp, amniotic fluid, and umbilical cord). In vitro, MSCs grow as adherent cells, display fibroblast-like morphology, and self-renew, undergoing specific mesodermal differentiation. High heterogeneity of MSCs from different origin, and differences in preparation techniques, make difficult to uniform their functional properties for therapeutic purposes. Immunomodulatory, migratory, and differentiation ability, fueled clinical MSC application in regenerative medicine, whereas beneficial effects are currently mainly ascribed to their secretome and extracellular vesicles. MSC translational potential in cancer therapy exploits putative anti-tumor activity and inherent tropism toward tumor sites to deliver cytotoxic drugs. However, controversial results emerged evaluating either the therapeutic potential or homing efficiency of MSCs, as both antitumor and protumor effects were reported. Glioblastoma (GBM) is the most malignant brain tumor and its development and aggressive nature is sustained by cancer stem cells (CSCs) and the identification of effective therapeutic is required. MSC dualistic action, tumor-promoting or tumor-targeting, is dependent on secreted factors and extracellular vesicles driving a complex cross talk between MSCs and GBM CSCs. Tumor-tropic ability of MSCs, besides providing an alternative therapeutic approach, could represent a tool to understand the biology of GBM CSCs and related paracrine mechanisms, underpinning MSC-GBM interactions. In this review, recent findings on the complex nature of MSCs will be highlighted, focusing on their elusive impact on GBM progression and aggressiveness by direct cell-cell interaction and via secretome, also facing the perspectives and challenges in treatment strategies.

Keywords: cancer stem cells; extracellular vesicles; glioblastoma; mesenchymal stem cells; secretoma.

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Conflict of interest statement

The authors declared no potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Cell‐cell interaction events in 2D monolayer cocultures of UC‐MSCs and GSCs mediated by the release of EVs by UC‐MSCs. Confocal fluorescence image of Dil‐stained UC‐MSC (red) cocultured with GSCs transfected with GFP (green): orange vesicles are found in some GSCs (white arrows)
FIGURE 2
FIGURE 2
Diagrammatic representation of the interactions between mesenchymal stem cells and glioblastoma cells, also involving other nonmalignant stromal and immune cells within the tumor microenvironment. In the figure, the critical pathways that may support or impair tumor growth via a variety of mechanisms are highlighted
See this image and copyright information in PMC

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