Potent tumor tropism of induced pluripotent stem cells and induced pluripotent stem cell-derived neural stem cells in the mouse intracerebral glioma model

Abstract

Although neural and mesenchymal stem cells have been well-known to have a strong glioma tropism, this activity in induced pluripotent stem cells (iPSCs) has not yet been fully studied. In the present study, we tested tumor tropic activity of mouse iPSCs and neural stem cells derived from the iPSC (iPS-NSCs) using in vitro Matrigel invasion chamber assay and in vivo mouse intracranial tumor model. Both iPSC and iPS-NSC had a similar potent in vitro tropism for glioma conditioned media. The migrated iPSCs to the gliomas kept expressing Nanog-GFP gene, suggesting no neuronal or glial differentiation. iPSCs or iPS-NSCs labeled with 5-bromo-2-deoxyuridine were intracranially implanted in the contralateral hemisphere to the GL261 glioma cell implantation in the allogeneic C57BL/6 mouse. Active migration of both stem cells was observed 7 days after implantation. Again, the iPSCs located in the tumor area expressed Nanog-GFP gene, suggesting that the migrated cells were still iPSCs. These findings demonstrated that both iPSCs and iPS-NSCs had potent glioma tropism and could be candidates as vehicles in stem cell-based glioma therapy.

Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies

“…Our studies indicate that ipNSCs and hiPNSCs secreting S‐TRAIL have strong anti‐tumor capacity, suggesting their resemblance to already existing NSC‐based therapies . These findings are generally in coherence with the findings of others . However, our studies are the first to demonstrate that combined expression of S‐TRAIL and HSV‐TK by sECM encapsulated NSCs generated from iPSCs have anti‐tumor efficacy in vivo.…”

Bi-specific molecule against EGFR and death receptors simultaneously targets proliferation and death pathways in tumors

“…We and others have previously shown that NSC and MSC migrate extensively toward tumors and therefore have an enormous therapeutic potential as gene delivery vehicles 43–47 . Most of the cancer cell lines used in this study were specifically chosen based on their unresponsiveness to death receptor agonist, TRAIL.…”

Stem Cell-Based Therapies for Cancer

“…Additionally, the iPSCs did not differentiate during migration. These findings suggest that iPSCs and their derivatives can be feasible candidates as vehicles in stem cell-based gene therapy for brain tumors (Yamazoe et al, 2015).…”