International Journal of Nanomedicine (Mar 2018)
A promising magnetic resonance stem cell tracer based on natural biomaterials in a biological system: manganese (II) chelated to melanin nanoparticles
Abstract
Shi-Jie Liu,1,2,* Ling-Jie Wang,1,* Ying Qiao,1 Hua Zhang,1 Li-Ping Li,1 Jing-Hua Sun,1 Sheng He,1 Wen Xu,1,2 Xi Yang,1 Wen-Wen Cai,2 Jian-Ding Li,1 Bin-Quan Wang,3 Rui-Ping Zhang2 1Medical Imaging Department, First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, China; 2Imaging Department, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; 3Department of Otolaryngology, Head & Neck Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China *These authors contributed equally to the paper Background: Melanin and manganese are both indispensable natural substances that play crucial roles in the human body. Melanin has been used as a multimodality imaging nanoplatform for biology science research because of its natural binding ability with metal ions (eg, 64Cu2+, Fe3+, and Gd3+). Because of its effects on T1 signal enhancement, Mn-based nanoparticles have been used in magnetic resonance (MR) quantitative cell tracking in vivo. Stem cell tracking in vivo is an essential technology used to characterize engrafted stem cells, including cellular viability, biodistribution, differentiation capacity, and long-term fate.Methods: In the present study, manganese(II) ions chelated to melanin nanoparticles [MNP-Mn(II)] were synthesized. The characteristics, stem cell labeling efficiency, and cytotoxicity of the nanoparticles were evaluated. MR imaging of the labeled stem cells in vivo and in vitro were also further performed. In T1 relaxivity (r1), MNP-Mn(II) were significantly more abundant than Omniscan. Bone marrow-derived stem cells (BMSCs) can be labeled easily by coincubating with MNP-Mn(II), suggesting that MNP-Mn(II) had high biocompatibility.Results: Cell Counting Kit-8 assays revealed that MNP-Mn(II) had almost no cytotoxicity when used to label BMSCs, even with a very high concentration (1,600 µg/mL). BMSCs labeled with MNP-Mn(II) could generate a hyperintense T1 signal both in vitro and in vivo, and the hyperintense T1 signal in vivo 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. Keywords: melanin, manganese, magnetic resonance imaging, mesenchymal stem cells, cell tracer