Cytotherapy · 2026
Isolation of adipose-derived mesenchymal stromal cells expressing soluble forms of GAS1 and PTEN for experimental cell therapy for glioblastoma.
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Tovar-Medina Gisela, Florán-Hernández Carla Daniela, Avalos-Fuentes José Arturo, Rodríguez-Cruz Fanny, Segovia José
Аннотация
BACKGROUND AIMS: Glioblastoma is the most frequent primary brain tumor, and its current treatment mainly prolongs survival, highlighting the need for more effective second-line therapies to improve patient prognosis. Stem cells represent a promising platform for developing cell-based therapies due to their biological characteristics, which enable the delivery of antitumoral agents. Still, there are some limitations, such as invasive delivery methods to overcome the blood-brain barrier, and the need for repeated administration, among others. Here, we propose a cellular therapy based on a stable adipose-derived mesenchymal stem cell line (Ad-MSC) genetically engineered to express the therapeutic genes tGAS1 and PTEN-L, tumor suppressors that interfere with signaling pathways associated with glioblastoma growth and survival, under tetracycline regulation.
METHODS: The therapeutic strategy was evaluated in both in vitro and in vivo glioblastoma models, with engineered Ad-MSCs administered intranasally in vivo to target glioblastoma tumors.
RESULTS: The therapeutic system showed tropism toward intracranially implanted tumors, inducible expression and release of tGAS1 and PTEN-L, and a significant reduction in tumor volume (p < 0.0001).
CONCLUSIONS: Thus, our data indicates that intranasal administration of Ad-MSC expressing inducible tGAS1 and PTEN-L, represents a promising alternative to overcome the limitations of therapies for glioblastoma.
METHODS: The therapeutic strategy was evaluated in both in vitro and in vivo glioblastoma models, with engineered Ad-MSCs administered intranasally in vivo to target glioblastoma tumors.
RESULTS: The therapeutic system showed tropism toward intracranially implanted tumors, inducible expression and release of tGAS1 and PTEN-L, and a significant reduction in tumor volume (p < 0.0001).
CONCLUSIONS: Thus, our data indicates that intranasal administration of Ad-MSC expressing inducible tGAS1 and PTEN-L, represents a promising alternative to overcome the limitations of therapies for glioblastoma.