Stmc-33. differential migration pathways of therapeutic stem cell carriers to glioma after intranasal delivery

Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) possess natural tropism to brain tumors. The unique stem cell intranasal delivery strategy bypasses the blood brain barrier and was recently demonstrated to convey therapeutic benefits in xenograft mouse models in conjunction with radiation and oncolytic virotherapy. It is imperative to understand the tumor tropism of therapeutic stem cells delivered intranasally to formulate optimal therapeutic strategies. To overcome the limitations of in vivo tracing of small number of stem cells delivered intranasally, we leveraged our mesoporous nanoparticle (MSN)-based radiolabeling technology to analyze NSCs and MSCs with MSN-Zr89 enabled Positron Emission Tomography (PET) with high sensitivity. PET imaging and immunocytochemistry demonstrated striking differences in the primary migration routes of MSCs and NSCs, in that MSCs predominantly migrated toward glioma xenografts through the caudal regions of the mouse brain, such as trigeminal ganglia, whereas NSCs predominantly migrated through the rostral regions of the brain, especially the olfactory bulbs. We hypothesize that the chemotaxic cytokine receptor profiles of NSCs and MSCs are major determinants in the migratory path in response to diverse brain micro-environmental cues, and genetic editing can augment tumor tropism. Mouse cytokine array analysis of brain tissue lysates collected from the olfactory bulbs and trigeminal ganglia showed EGF as a top candidate of responsib...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: STEM CELLS Source Type: research