Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI

TLDR

Noninvasive monitoring of stem cells using high‑resolution molecular imaging will be instrumental to improve clinical neural transplantation strategies. Knowledge of migration patterns and implementation of noninvasive stem cell tracking might help to improve the design of future clinical neural stem cell transplantation. Magnetic‑nanoparticle labeling of human CNS stem cells does not impair survival, migration, differentiation, or electrophysiology, and MRI tracking reveals that transplanted cells adapt to neonatal, adult, or injured brain environments with distinct migration patterns, survive long‑term, differentiate site‑specifically like unlabeled cells, and that graft location influences migration while MR signals characterize cell death and clearance.

Abstract

Noninvasive monitoring of stem cells, using high-resolution molecular imaging, will be instrumental to improve clinical neural transplantation strategies. We show that labeling of human central nervous system stem cells grown as neurospheres with magnetic nanoparticles does not adversely affect survival, migration, and differentiation or alter neuronal electrophysiological characteristics. Using MRI, we show that human central nervous system stem cells transplanted either to the neonatal, the adult, or the injured rodent brain respond to cues characteristic for the ambient microenvironment resulting in distinct migration patterns. Nanoparticle-labeled human central nervous system stem cells survive long-term and differentiate in a site-specific manner identical to that seen for transplants of unlabeled cells. We also demonstrate the impact of graft location on cell migration and describe magnetic resonance characteristics of graft cell death and subsequent clearance. Knowledge of migration patterns and implementation of noninvasive stem cell tracking might help to improve the design of future clinical neural stem cell transplantation.