Tracking of Autologous VSOP-Labeled Mesenchymal Stem Cells in the Sheep Brain Using 3.0 T MRI
Assessment of biodistribution and monitoring of cell migration processes in vivo are essential for the safety of novel cell-based therapies for ischemic stroke and early-stage clinical trials, but are mainly lacking investigation in large animal models which are closer to the situation found in human patients. This chapter reports a series of experiments which establish a MRI-sensitive labeling procedure for autologous ovine mesenchymal stem cells (MSC) and the assessment of in vivo and in vitro detection limits of the cells at 3.0 T. Cell migration was monitored after intravenous transplantation following experimental stroke in sheep. Cell detection was feasible at 3.0 T with detection lim…
Optogenetics in Stem Cell Research: Focus on the Central Nervous System
Stem cell-based therapies of CNS disorders represent a promising approach in translational and regenerative medicine. Stem cell-based tissue replacement and regeneration would, for the first time, offer a causal treatment strategy which is most likely not bound to a specific time window. Therapeutic strategies relying on this paradigm would require administration of exogenous stem cells to the CNS and/or the augmentation of endogenous stem cell capabilities. However, it remains unclear whether tissue replacement or bystander effects are required to induce such effects. Conventional experimental techniques will not be able to causally reveal such information, due to the complexity and coinci…
A Safe and Effective Magnetic Labeling Protocol for MRI-Based Tracking of Human Adult Neural Stem Cells
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 differentiatio…
Imaging of VSOP labeled stem cells in agarose phantoms with susceptibility weighted and T2* weighted MR Imaging at 3T: determination of the detection limit.
Objectives This study aimed to evaluate the detectability of stem cells labeled with very small iron oxide particles (VSOP) at 3T with susceptibility weighted (SWI) and T2* weighted imaging as a methodological basis for subsequent examinations in a large animal stroke model (sheep). Materials and Methods We examined ovine mesenchymal stem cells labeled with VSOP in agarose layer phantoms. The experiments were performed in 2 different groups, with quantities of 0–100,000 labeled cells per layer. 15 different SWI- and T2*-weighted sequences and 3 RF coils were used. All measurements were carried out on a clinical 3T MRI. Images of Group A were analyzed by four radiologists blinded for the num…