An MRI-visible mesenchymal stem cell therapy reinvigorates T lymphocytes in glioblastoma

Motivation: Immunotherapy resistance in glioblastoma (GBM) has been linked to a paucity of tumor-infiltrating T lymphocytes and concurrent T-cell dysfunction. Goal(s): This research aims to determine whether MRI-visible mesenchymal stem cells (MSCs) could be employed for GBM immunotherapy. Approach: CXCL10-Nrf2-FTH-MSCs with enhanced T lymphocyte recruitment (Cxcl10 gene), oxidative stress tolerance (Nrf2 gene), and MRI visibility (Fth gene) were genetically engineered. With the guidance of FTH-MRI, these MSCs were injected into the tumor periphery of orthotopic GL261 GBMs in mice. Results: In vivo MRI monitoring and histology examinations demonstrated that CXCL10-Nrf2-FTH-MSCs can significantly limit GBM growth by reviving T lymphocytes within the tumor. Impact: FTH-MRI is a practical method for guiding intracranial stem cell transplantation. MRI-guided peritumoral implantation of CXCL10-Nrf2-FTH-MSCs provides a novel immunotherapeutic approach based on tumoricidal stem cells for the treatment of GBM.