Some cell phones come equipped with global positioning systems that inform parents of their child's location. Clinicians would benefit from similar information about stem cells. Stem cell grafts are proposed treatments for Parkinson's disease, Huntington's disease and stroke, but there is currently no way to track the progress of stem cells once they are implanted. Now Guzman et al. report non-invasive imaging of human stem cells implanted in the mouse brain in a recent article in Proceedings of the National Academy of Sciences.
Superparamagnetic iron oxide (SPIO) nanoparticles are contrast agents for magnetic resonance imaging (MRI). Feridex is a dextran-coated SPIO agent that has been approved by the Food and Drug Administration for use in humans.
Neurospheres are non-adherent aggregates of neural precursor cells. The authors labeled neurospheres derived from human central nervous system stem cells (hCNS-SCns) with Feridex. Feridex- and vehicle-treated neurospheres showed similar viability and proliferation. With each round of cell division, cellular SPIO content reduced by half. After exposure to differentiating conditions, current injection produced identical action potentials in Feridex- and vehicle-treated cells, suggesting that SPIO did not adversely affect hCNS-SCns.
In the mouse olfactory system, the progeny from endogenous stem cells migrate from the subventricular zone to the olfactory bulb along the rostral migratory stream. Do exogenous stem cells migrate similarly? The authors implanted hCNS-SCns in the newborn mouse brain. Three weeks later, T2-weighted MRI showed SPIO-labeled cells in the rostral migratory stream. Subsequent MRIs showed SPIO-labeled hCNS-SCns cells in the olfactory glomerulus as well as the corpus callosum, hippocampus and cortex. Consistent with these findings, the authors also found cells positive for the human-specific antigen SC121 in these brain regions. SC121 did not colocalize with the panmonocytic marker Iba-1, suggesting that implanted hCNS-SCns were not cleared by macrophages.
In the adult brain, implanted stem cells migrate only following injury. The authors implanted hCNS-SCns in the adult mouse brain seven days after a stroke. Five weeks later, T2-weighted MRI showed hCNS-SCns migrating toward the injury site. In contrast, hCNS-SCns did not migrate in animals that received grafts many millimeters away from the injury site. Post-stroke survival rates were similar for mice treated with SPIO-labeled and control grafts.
MRI showed the clearance of dead stem cells. The authors subjected hCNS-SCns to several cycles of freezing and thawing. They implanted these cells in the left striatum and viable hCNS-SCns in the right striatum. Although both left and right striatum initially looked similar in T2-weighted MRI images, signal intensity declined in the left relative to the right striatum over the 35-day observation period, suggesting that this method could be used to quantify the viability of stem cell transplants over time. Similarly, striatal Feridex injections might allow clinicians to quantify disease progress by assessing the viability of dopaminergic cells in people with Parkinson's disease.