Neurotransplantation of magnetically labeled oligodendrocyte progenitors: Magnetic resonance tracking of cell migration and myelination

Abstract

Demyelination is a common pathological finding in human neurological diseases and frequently persists as a result of failure of endogenous repair. Transplanted oligodendrocytes and their precursor cells can (re)myelinate axons, raising the possibility of therapeutic intervention. The migratory capacity of transplanted cells is of key importance in determining the extent of (re)myelination and can, at present, be evaluated only by using invasive and irreversible procedures. We have exploited the transferrin receptor as an efficient intracellular delivery device for magnetic nanoparticles, and transplanted tagged oligodendrocyte progenitor cells into the spinal cord of myelin-deficient rats. Cell migration could be easily detected by using three-dimensional magnetic resonance microscopy, with a close correlation between the areas of contrast enhancement and the achieved extent of myelination. The present results demonstrate that magnetic resonance tracking of transplanted oligodendrocyte progenitors is feasible; this technique has the potential to be easily extended to other neurotransplantation studies involving different precursor cell types. Demyelination is an important pathological component of multiple sclerosis and other neurological disorders. Recent research has suggested that it is possible to promote (re)myelination in animal models of abnormal myelination or demyelination (1-3), either by endogenous oligodendrocytes or exogenous myelinating cells. The latter repair mechanism has received particular attention, because it has been shown that transplanted oligodendrocyte precursor cells can myelinate large areas in the central nervous system (4). A similar therapeutic approach in humans may be pursued and is supported by the safety and effectiveness of human neurotransplantation studies (5, 6). The clinical outcome of such studies will be directly determined by the extent of myelination, and thus by the immediate dispersion, migratory capacity, and long-term survival of grafted cells. A technique that could monitor the grafted cell migration continuously and noninvasively is crucial to guide further advances in neurotransplantation research. We hypothesized that tagging grafted cells with a magnetic label might allow magnetic resonance (MR) tracking of their migratory capacity, not unlike an earlier MR microscopy study that used labeled progeny cells to follow cell movements and lineages in the developing embryo (7). Magnetically labeled cells previously have received interest to study neural grafting procedures (8, 9) and cellular trafficking (10-13) by MR imaging.Oligodendrocyte progenitors have a greater migratory and myelinating capacity than mature glial cells (14, 15). We therefore chose the rat oligodendrocyte progenitor cell line 17) as the graft, with the myelin-deficient (md) rat as a recipient, because the migration pattern of LacZ ϩ CG-4 cells has been documented in detail with this model (18). The md rat carries an X-linked recessive mutation in the proteolipid protein gene and is characteriz...

Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging

“…27 Bulte and coworkers utilized anti-transferrin receptor antibodies conjugated to nanoparticles in order to observe oligodendrocyte migration postneurotransplantation. 19 The SPIO did not interfere with the cells' ability to myelinate in vivo, and histological evaluation of the cells with nanoparticles revealed cell migration up to 10 mm in 14 days.…”

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

“…Only very small movement of the transplanted cells was detected between 1 and 6 weeks (compare Figures 2E with 2F and 2G for cell localization). Expanded dark areas (such as a and b in Figures 2F and 2G) appeared at later time points (between 2 and 6 weeks) for all cell treated animals and this indicated that the grafted cells were alive (Bulte et al, 1999;Zhang et al, 2003a). Double immunohistochemistry staining revealed that Prussian blue positive cells within the ischemic boundary zone were not co-localized to EBA positive vessels (Figures 3A-3C) and GFAP positive cells (Figures 3D-3F).…”

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

“…Other strategies for developing MR contrast agents that are easy to detect include the utilization of viral protein cages 44 or the use of internalizing monoclonal antibodies. 45 Cells in suspension can be labeled using magnetoelectroporation. 46 The Use of MSCs in the Treatment of CNS Disorders Preclinical studies.…”