A Safe and Effective Magnetic Labeling Protocol for MRI-Based Tracking of Human Adult Neural Stem Cells

Frontiers in Neuroscience

Roland Coras¹  Ingmar Blümcke¹  Claus Zimmer²  Annette Förschler²  Donald Lobsien³  Jürgen Schlegel⁴  Saida Zoubaa⁴  Albrecht Stroh⁵  Jenny Kressel⁶  Johannes Boltze⁸  Wenke Fröhlich⁹  Antje Y. Dreyer⁹ 

[1] Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany;Department of Neuroradiology, Technical University Munich, Munich, Germany;Department of Neuroradiology, University Hospital Leipzig, Leipzig, Germany;Division of Neuropathology, Institute of Pathology, Technical University of Munich, Munich, Germany;German Resilience Center, Mainz, Germany;Helmholtz Center Munich, Institute for Biological and Medical Imaging, Munich, Germany;Institute for Pathophysiology, Mainz University, Mainz, Germany;School of Life Sciences, University of Warwick, Coventry, United Kingdom;Translational Center for Regenerative Medicine, Fraunhofer Institute for Cell Therapy and Immunology, University of Leipzig, Leipzig, Germany;

关键词: human adult stem cells;    magnetic labeling;    MRI;    cell tracking;    CNS – disorder;   

DOI  :  10.3389/fnins.2019.01092

来源: DOAJ

【 摘 要 】

Magnetic resonance imaging (MRI) provides a unique tool for in vivo visualization and tracking of stem cells in the brain. This is of particular importance when assessing safety of experimental cell treatments in the preclinical or clinical setup. Yet, specific imaging requires an efficient and non-perturbing cellular magnetic labeling which precludes adverse effects of the tag, e.g., the impact of iron-oxide-nanoparticles on the critical differentiation and integration processes of the respective stem cell population investigated. In this study we investigated the effects of very small superparamagnetic iron oxide particle (VSOP) labeling on viability, stemness, and neuronal differentiation potential of primary human adult neural stem cells (haNSCs). Cytoplasmic VSOP incorporation massively reduced the transverse relaxation time T2, an important parameter determining MR contrast. Cells retained cytoplasmic label for at least a month, indicating stable incorporation, a necessity for long-term imaging. Using a clinical 3T MRI, 1 × 103 haNSCs were visualized upon injection in a gel phantom, but detection limit was much lower (5 × 104 cells) in layer phantoms and using an imaging protocol feasible in a clinical scenario. Transcriptional analysis and fluorescence immunocytochemistry did not reveal a detrimental impact of VSOP labeling on important parameters of cellular physiology with cellular viability, stemness and neuronal differentiation potential remaining unaffected. This represents a pivotal prerequisite with respect to clinical application of this method.

【 授权许可】

Unknown