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

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-m 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.embryonic stem cells ͉ cerebral ischemia ͉ cell labeling S everal studies have been able to demonstrate the migrational capacity of endogenous stem or progenitor cells in rat and mouse brains during normal (1, 2) and pathophysiological conditions (3, 4). The therapeutical potential of stem cell grafting has recently been studied in various pathological conditions of the brain showing extensive cell migration after implantation. However, all investigations so far have required the invasive analysis of brain sections postmortem in various groups of animals for different survival periods. A recent investigation described the detection of labeled cells, injected into rats, but reported no specific cell migration in the in vivo MRI data (5). All other studies have investigated the potential of MRI to detect pretreated cells (5-7) by registering the MRI data ex vivo, thus permitting observation of only one time point. In the present investigation we demonstrate sufficient spatial and temporal resolution of experimental MRI at high fields to allow longitudinal studies on individual animals after stem cell implantation into the brain. We have investigated the spatial dynamics of implanted embryonic stem (ES) cells and demonstrated their high migrational potential from the implantation site in the normal brain hemisphere toward the ischemic le...

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

“…This leads to the hypothesis that therapeutic neovascularization may be required to achieve optimal "take" of transplanted neuronal precursors in the setting of ischemia. Although the current data bear most directly on the endogenous neuronal response to cerebrovascular ischemia, it is possible that enhanced formation of neovasculature may also be important for survival of embryonic (39) and neural (40) stem cell transplants in other circumstances, such as neurodegenerative disorders.…”

Migration, fate and in vivo imaging of adult stem cells in the CNS

“…35 On the day that nanoparticles were withdrawn, the efficiency of both rat or human MSC labeling (i.e., how many cells out of the total number of analyzed cells were labeled) was 50-70%. Another labeling approach is based on combining a commercially available dextran-coated SPIO, such as Feridex s36 or Sinerem s , 37 and a commercially available transfection agent, for example, Superfectt poly-L-lysine, Lipofectamin or Fugenet. 35,38 Transfection agents effectively transport nanoparticles into cells through electrostatic interactions.…”

Ischemic Cerebral Tissue Response to Subventricular Zone Cell Transplantation Measured by Iterative Self-Organizing Data Analysis Technique Algorithm

“…Magnetic resonance imaging (MRI) provides a noninvasive and dynamic means to monitor the hemodynamic and biophysical events in cerebral tissue (Jiang et al, 2000(Jiang et al, , 1998 and can track magnetically labeled cells in vivo (Zhang et al, 2003a, b;Hoehn et al, 2002;Bulte et al, 1999). ISODATA (Iterative Self-Organizing Data Analysis Technique Algorithm) is a data processing technique based on cluster analysis in the feature space (Ball and Hall, 1967).…”