Biocompatible fluorescent nanoparticles forin vivostem cell tracking

Abstract

Efficient application of stem cells to the treatment of neurodegenerative diseases requires safe cell tracking to follow stem cell fate over time in the host environment after transplantation. In this work, for the first time, fluorescent and biocompatible methyl methacrylate (MMA)-based nanoparticles (fluoNPs) were synthesized through a free-radical co-polymerization process with a fluorescent macromonomer obtained by linking Rhodamine B and hydroxyethyl methacrylate. We demonstrate that the fluoNPs produced by polymerization of MMA-Rhodamine complexes (1) were efficient for the labeling and tracking of multipotent human amniotic fluid cells (hAFCs); (2) did not alter the main biological features of hAFCs (such as viability, cell growth and metabolic activity); (3) enabled us to determine the longitudinal bio-distribution of hAFCs in different brain areas after graft in the brain ventricles of healthy mice by a direct fluorescence-based technique. The reliability of our approach was furthermore confirmed by magnetic resonance imaging analyses, carried out by incubating hAFCs with both superparamagnetic iron oxide nanoparticles and fluoNPs. Our data suggest that these finely tunable and biocompatible fluoNPs can be exploited for the longitudinal tracking of stem cells.

Tracking of Fluorescently Labeled Polymer Particles Reveals Surface Effects during Shear-Controlled Aggregation

“…Synthesis and Purification of the Rh B-HEMA Precursor. The synthesis method was adapted from the study of Cova et al 19 The Rh B-HEMA precursor was synthesized by Steglich esterification. In a flask, 4 g of Rh B was dissolved in 80 mL of acetonitrile.…”

Soft fluorescent nanomaterials for biological and biomedical imaging

“…Surfactants such as PEG and Tween 80 also are used to stabilize the polymerized organic NPs which give good biocompatibility for nonspecific imaging. 54, 56, 57 …”

“…The particles are stabilized by either surfactants, 43, 56 amphiphilic polymers 78 or PEG 41, 93 . By tracking the fluorescent trail of organic NPs, objects of interest can be imaged in vivo .…”

“…For example, human amniotic fluid cells labeled with RhB-doped polymer NPs were grafted in the brain ventricles of healthy mice, and the longitudinal bio-distribution of the human amniotic fluid cells in different brain areas were determined by fluorescence imaging. 56 …”

Technology Advancement for Integrative Stem Cell Analyses

“…113,114 With continuous improvements in labeling technologies for molecular imaging and approaches to track specific cellular components, the long-term monitoring of signals, instead of being restricted to discrete time points, will enable tracing of cellular behaviors for both in vitro and in vivo processes. [115][116][117] In vitro experimental design has the disadvantage of shortterm observation ( <48 h) due to the limited space. This spatial problem fundamentally cannot be avoided when analyzing events that occur over long-term periods from hours to a few weeks, such as differentiation of stem cells.…”