Acquired mitochondria confer chemoresistance to Glioblastoma stem cells

Glioblastomas are heterogeneous tumors with high metabolic plasticity. Their poor prognosis is linked to glioblastoma stem cells (GSCs) which acquire resistance to temozolomide (TMZ) chemotherapy. We show that mesenchymal stem cells (MSCs) transfer mitochondria to GSCs through tunneling nanotubes and that MSC mitochondria enhance GSCs survival to TMZ. MSC mitochondria disrupt GSC transcriptional response to TMZ, especially for DNA damage and metabolism, and alter metabolism of TMZ-treated GSCs. This results in increased OXPHOS and a shift in nutrient use from glucose to glutamine. Therefore, MSC mitochondria are a master trigger of cancer cell chemoresistance through metabolic remodeling.