Induced pluripotent stem cells (iPSCs) s form cancerous teratomas when implanted in vivo have limited the application of iPSC and iPSC-derived cell transplant therapies. With the recent development of transdifferentiation (TD), where somatic cells are directly reprogrammed into an alternate lineage bypassing dedifferentiation into a pluripotent state, reprogramming technology now stands poised to achieve safe personalized cell transplant therapy.
The newest addition to the cell types created by TD is neural stem cells (NSCs), called induced NSCs (iNSCs). iNSCs were found to express nestin and differentiate into astrocytes, neurons and oligodendrocytes similar to brain-derived NSCs. Yet, unlike NSCs derived from embryonic stem cells or iPSCs, iNSCs showed no cancerous teratoma formation in vivo. This suggests that iNSCs can provide safe, routine, patient-specific cell transplantation therapy to treat disorders of the central nervous system (CNS). However, the efficacy of iNSC-based therapy remains to be defined.
Researchers in the journal Nature Communications provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer.
They find that iNSCs genetically engineered with optical reporters and tumoricidal gene products retain the capacity to differentiate and induced apoptosis in co-cultured human glioblastoma cells. Time-lapse imaging shows that iNSCs are tumoritropic, homing rapidly to co-cultured glioblastoma cells and migrating extensively to distant tumur foci in the murine brain.
Multimodality imaging reveals that iNSC delivery of the anticancer molecule TRAIL decreases the growth of established solid and diffuse patient-derived orthotopic glioblastoma xenografts 230- and 20-fold, respectively, while significantly prolonging the median mouse survival.
These findings establish a strategy for creating autologous cell-based therapies to treat patients with aggressive forms of brain cancer.