Abstract
Stem cells are capable of replication and differentiation so that they are widely studied for its potential application for tissue engineering and transplantation.Once stem cells are delivered into human body,it is hard to detect its existence and trace its migration route between different organs.Paramagnetic and superparamagnetic substances are used for labeling stem cells that could be visualized under magnetic resonance imaging(MRI).However,the efficacy,sensitivity and feasibility between paramagnetic and superparamagnetic substances labeling are not fully investigated. We investigated paramagnetic and superparamagnetic substance labeling by choosing clinically widely used gadolinium chelates as choice for paramagnetic contrast agent and iron oxide nanoparticles as candidate for superparamagnetic substance because the toxicity and adverse effects to the cells are previously widely studied.The gadolinium chelates and iron oxide nanoparticles are labeled into human mesenchymal stem cell line at different concentration and the optimized concentration was determined by maintaining cell viability the same as cells without labeling.Under optimized concentration,labeled cells at numbers from 1000 to 2×10~5 are placed into test tubes for MRI visualization.The minimal cell numbers that could be detected by clinical MRI was determined.These cells are further injected into bilateral flank of living mouse.Under clinical 1.5 Tesla MRI scanning,the images are evaluated for stem cell detecting ability. We found there is 8 fold sensitivity increases in cells labeled with iron oxide nanoparticles,which has detecting limit of 12500 cells whereas only 50000 or more cells could be detected in gadolinium chelates labeled cells.Under living animal study,although iron oxide nanoparticle labeled stem cells could be detected 8 times more sensitive,the magnetic susceptibility artifact interrupted the visualization of adjacent organ structures.We conclude that labeling stem cells with superparamagnetic substance is more efficacious,but in case evaluation of organ structure is critical,paramagnetic labeling is more favorable.These finding would be beneficial for development of stem cell biology and tissue engineering.