Cellular multiparametric MRI of neural stem cell therapy in a rat glioma model

Cellular multiparametric magnetic resonance imaging (MRI) provided an in vivo visualisation of neural stem cells' (NSCs) tropism for gliomas in the rat brain. NSCs were magnetically labelled in vitro with the bimodal gadolinium-based contrast agent, gadolinium rhodamine dextran (GRID), and injected into the contralateral hemisphere to the developing tumour. Contrast-to-noise measurements showed that GRID-labelled cells induced a signal attenuation on both T2-, T2*weighted images, and a modest signal gain on TI-weighted images. Tumour development and progression were longitudinally monitored in vivo by serial MR scanning. Measurements of turnour volume and turnour progression over time in terms of tumour doubling time showed a tendency towards a reduced tumour growth in NSC-treated animals. MR findings of migration and infiltration of turnours by labelled NSCs were corroborated with immunohistopathology, where labelled cells were detected in the corpus callosurn at the tumour border and dispersed in the solid turnour tissue. Immunohistopathology also revealed that macrophages invaded the tumour tissue and in some cases engulfed GRID-labelled stem cells. No significant difference in macrophage recruitment between NSC-treated and vehicle-treated animals were detected, indicating that magnetically labelled NSC do not increase macrophage invasion of tumour tissue. Our findings demonstrate that cellular multiparametric MRI provides a valuable tool for in vivo dynamic monitoring of tumour-directed neural stem cell migration as well as therapeutic efficacy. (c) 2007 Elsevier Inc. All rights reserved.