Abstract
Stem Cell (SC) therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1) the main physical parameters of SPIOn were maintained over time; 2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not influence mice survival.
Highlights
The evidence that Amyotrophic Lateral Sclerosis (ALS) involves areas apart from the motor system supports the idea of a multisystemic disease, affecting multiple cell types, which requires therapeutic treatments able to provide an healthy environment for degenerating motor neurons and capable of enhancing endogenous repair [1]
We described for the first time the paramagnetic labeling of hAFCs and their subsequent long-term tracking in a chronic neuro-degenerative/inflammatory environment, such as wobbler mice brains
We demonstrated that hAFC survival was not altered by the presence of double tracers, permitting substantial correlations between in vivo and ex vivo data at different times
Summary
The evidence that Amyotrophic Lateral Sclerosis (ALS) involves areas apart from the motor system supports the idea of a multisystemic disease, affecting multiple cell types, which requires therapeutic treatments able to provide an healthy environment for degenerating motor neurons and capable of enhancing endogenous repair [1]. To intravenous delivery [7], no migration towards the spinal cord was observed, confirming that the beneficial role of transplanted cells is independent from their permanence in the site of administration and their distribution in degenerating host tissues. In spite of the encouraging cell grafting results in murine models of ALS, a careful investigation into the interaction between transplanted cells and host tissues is an interesting missing part of preclinical studies. In this context, several SC labeling strategies have been proposed. Super Paramagnetic Iron Oxides nanoparticles (SPIOn) appeared promising for tracking different types of SCs [13]
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