Journal Article

Transcriptional landscape of the interaction of human Mesenchymal Stem Cells with Glioblastoma in bioprinted co-cultures

Landais, Yuna, Vallette, François M., Gratas, Catherine, Serandour, Aurelien, Oliver, Lisa, Paris, François, Heymann, Dominique, Cartron, Pierre-François

2024

Overview

Background The interaction between mesenchymal stem cells (MSC) and Glioblastoma (GBM), although potentially of the highest importance, is ill-understood. This is due, in part, to the lack of relevant experimental models. The similarity between the in vitro situations and the in vivo situation can be improved by 3D co-culture as it reproduces key cell–cell interactions between the tumor microenvironment (TME) and cancer cells. Methods MSC Can acquired characteristics of cancer associated fibroblasts (CAF) by being cultured with conditioned medium from GBM cultures and thus are called MSC CAF . We co Cultured MSC CAF with patient derived GBM in a scaffold 3D bioprinted model. We studied the response to current GBM therapy (e.g. Temozolomide + /Radiation) on the co cultures by bulk transcriptomic (RNA Seq) and epigenetic (ATAC Seq) analyses Results The transcriptomic modifications induced by standard GBM treatment in bioprinted scaffolds of mono- or co-cultures of GBM ± MSC can be analyzed. We found that mitochondrial encoded OXPHOS genes are overexpressed under these conditions and are modified by both co-culture and treatment (chemotherapy ± radiation). We have identified two new markers of MSC/GBM interactions, one epigenetically regulated (i.e. TREM-1) associated with an increased overall survival in GBM patients and another implicated in post-transcriptional regulation (i.e. the long non-coding RNA, miR3681HG), which is associated with a reduced overall survival in GBM patients.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: 3D tumor model / Analysis / Anopheles / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Bioprinting / Bioprinting - methods / Brain Neoplasms - genetics / Brain Neoplasms - metabolism / Brain Neoplasms - pathology / Cancer / Cancer-Associated Fibroblasts - metabolism / Cancer-Associated Fibroblasts - pathology / Cell Biology / Cell Communication / Chemotherapy / Co-culture / Coculture Techniques / Epigenetic inheritance / Genes / Genetic aspects / Genetic transcription / Glioblastoma / Glioblastoma - genetics / Glioblastoma - metabolism / Glioblastoma - pathology / Glioblastoma multiforme / Humans / Life Sciences / Mesenchymal Stem Cells - cytology / Mesenchymal Stem Cells - metabolism / Mesenchymal stromal/stem cell / Regenerative Medicine/Tissue Engineering / Response to treatment / Stem Cells / Temozolomide - pharmacology / Temozolomide - therapeutic use / Tumor Microenvironment