The progress of using gadolinium (Gd)-based nanoparticles in cellular tracking lags behind that of superparamagnetic iron oxide (SPIO) nanoparticles in magnetic resonance imaging (MRI). Here, dual functional Gd-fluorescein isothiocyanate mesoporous silica nanoparticles (Gd-Dye@MSN) that possess green fluorescence and paramagnetism are developed in order to evaluate their potential as effective T1-enhancing trackers for human mesenchymal stem cells (hMSCs). hMSCs are labeled efficiently with Gd-Dye@MSN via endocytosis. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes, osteocytes, and chondrocytes, which can still be readily MRI detected. Imaging, with a clinical 1.5-T MRI system and a low incubation dosage of Gd, low detection cell numbers, and short incubation times is demonstrated on both loaded cells and hMSC-injected mouse brains. This study shows that the advantages of biocompatibility, durability, high internalizing efficiency, and pore architecture make MSNs an ideal vector of T1-agent for stem-cell tracking with MRI.
Parkinson's disease (PD) is a prevalent neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons. With their migration capacity toward the sites of diseased DA neurons in the PD brain, mesenchymal stem cells (MSCs) have the potential to differentiate to DA neurons for the replacement of damaged neurons and to secrete neurotrophic factors for the protection and regeneration of diseased DA neurons; therefore MSCs show promise for the treatment of PD. In this study, for the first time, we demonstrate that dextran-coated iron oxide nanoparticles (Dex-IO NPs) can improve the therapeutic efficacy of human MSCs (hMSCs) in a mouse model of PD induced by a local injection of 6-hydroxydopamine (6-OHDA). In situ examinations not only show that Dex-IO NPs can improve the rescue effect of hMSCs on the loss of host DA neurons but also demonstrate that Dex-IO NPs can promote the migration capacity of hMSCs toward lesioned DA neurons and induce the differentiation of hMSCs to DA-like neurons at the diseased sites. We prove that in vitro Dex-IO NPs can enhance the migration of hMSCs toward 6-OHDA-damaged SH-SY5Y-derived DA-like cells, induce hMSCs to differentiate to DA-like neurons in the conditioned media derived from 6-OHDA-damaged SH-SY5Y-derived DA-like cells and promote the protection/regeneration effects of hMSCs on 6-OHDA-damaged SH-SY5Y-derived DA-like cells. We confirm the potential of MSCs for cell-based therapy for PD. Dex-IO NPs can be used as a tool to accelerate and optimize MSC therapeutics for PD applicable clinically.
Superparamagnetic iron oxide (SPIO) nanoparticles show promise as labels for cellular magnetic resonance imaging (MRI) in the application of stem cell-based therapy. However, the unaddressed concerns about the impact of SPIO nanoparticles on stem cell attributes make the feasibility of SPIO labeling uncertain. Here, we show that the labeling of human mesenchymal stem cells (hMSCs) with ferucarbotran can induce epidermal growth factor receptor (EGFR) overexpression. Labeled hMSCs with their overexpressed EGFR were attracted by tumorous EGF and more effectively migrated toward tumor than unlabeled cells, resulting in more potent intrinsic antitumor activity. Moreover, the captured binding of tumorous EGF by overexpressed EGFR of labeled hMSCs blocked EGF/EGFR signaling-derived tumor growth, tumorous angiogenesis, and tumorous VEGF expression also responsible for tumor progression and development. Our results show that the impact of SPIO nanoparticles on stem cell attributes is not necessarily harmful but can be cleverly used to be beneficial to stem cell-based therapy.
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