A Promising Magnetic Resonance Stem Cell Tracer Based On Natural Biomaterials In A Biological System:Manganese(Ⅱ) Chelated To Melanin Nanoparticles

Objective:To understand the distribution,differentiation and survival status of stem cells in the host,they need to be monitored by the imaging equipment.Magnetic resonance imaging technology has no ionizing radiation,high resolution and widely clinical application,may be an ideal method to monitor stem cells.To identify stem cells within the tissue on the image,the cells need to be labeled with a tracer.Both melanin and manganese are natural substances indispensable to human body.In this study,melanin nanoparticles（MNPs）were chelated with manganese ions(Mn²⁺)to obtain a low toxicity nanometer stem cell tracer.Methods:In this study,melanin nanoparticles（MNPs）were successfully chelated with manganese ions(Mn²⁺)to obtain melanin-manganese nanoparticles[MNP-Mn（Ⅱ）];Their morphology and size was observed by transmission electron microscopy（TEM）;dynamic light scattering（DLS）was used to determined their hydration particle size and distribution characteristics;Determination of MNP-Mn（Ⅱ）solution T1 relaxation rate;Determination of stem cell labeling efficiency and cytotoxicity,and the intracellular distribution of MNP-Mn（Ⅱ）in the labeled stem cells;Magnetic resonance（MR）imaging of labeled stem cells in vitro and in vivo.Results:TEM images and sizes distribution of DLS showed monodispersed spherical nanoparticles of approximately 5 nm.The relaxation efficiency was high and the relaxation rate of T1 was 19.916mM^-1S^-1.MNP-Mn²⁺was almost non-toxic to stem cells;MNP-Mn（Ⅱ）labeled BMSCs produced high signal T1 signal both in vitro and in vivo,and in vivo high signal persisted for at least 28 days.Conclusion:Taken together,our results showed that MNP-Mn（Ⅱ）possessed many excellent properties for potential quantitative stem cell tracking in vivo.