Isolation of adipose-derived mesenchymal stromal cells expressing soluble forms of GAS1 and PTEN for experimental cell therapy for glioblastoma.

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.