Monitoring of implanted stem cell migration <i>in vivo</i> : A highly resolved <i>in vivo</i> magnetic resonance imaging investigation of experimental stroke in rat

TLDR

In vivo monitoring of grafted stem cells is essential to understand their migration, differentiation, and regenerative potential, yet prior studies relied on invasive histology rather than live imaging. The study aims to demonstrate that stem cell migration can be observed noninvasively over time within individual animals. Embryonic stem cells expressing GFP were labeled with an MRI contrast agent, implanted into rat brains after inducing focal ischemia, and tracked with 78‑μm isotropic MRI, confirmed by GFP registration. Over three weeks the labeled cells migrated along the corpus callosum to the ventricular walls and densely populated the contralateral lesion border, showing high migrational dynamics and validating the MRI approach for noninvasive tracking of migration, engraftment, and differentiation.

Abstract

In vivo monitoring of stem cells after grafting is essential for a better understanding of their migrational dynamics and differentiation processes and of their regeneration potential. Migration of endogenous or grafted stem cells and neurons has been described in vertebrate brain, both under normal conditions from the subventricular zone along the rostral migratory stream and under pathophysiological conditions, such as degeneration or focal cerebral ischemia. Those studies, however, relied on invasive analysis of brain sections in combination with appropriate staining techniques. Here, we demonstrate the observation of cell migration under in vivo conditions, allowing the monitoring of the cell dynamics within individual animals, and for a prolonged time. Embryonic stem (ES) cells, constitutively expressing the GFP, were labeled by a lipofection procedure with a MRI contrast agent and implanted into rat brains. Focal cerebral ischemia had been induced 2 weeks before implantation of ES cells into the healthy, contralateral hemisphere. MRI at 78-μm isotropic spatial resolution permitted the observation of the implanted cells with high contrast against the host tissue, and was confirmed by GFP registration. During 3 weeks, cells migrated along the corpus callosum to the ventricular walls, and massively populated the borderzone of the damaged brain tissue on the hemisphere opposite to the implantation sites. Our results indicate that ES cells have high migrational dynamics, targeted to the cerebral lesion area. The imaging approach is ideally suited for the noninvasive observation of cell migration, engraftment, and morphological differentiation at high spatial and temporal resolution.