MRI/PAI Dual-modal Imaging-guided Precise Tracking of Bone Marrow-derived Mesenchymal Stem Cells Labeled with Nanoparticles for Treating Liver Cirrhosis

Feng-Yong Liu; Ming Shi; Xin Li; Hong-Jun Yuan; Xiao-Mei Tian; Yi-Mao Xia; Min Zhou; Fu-Sheng Wang

doi:10.14218/JCTH.2021.00580

MRI/PAI Dual-modal Imaging-guided Precise Tracking of Bone Marrow-derived Mesenchymal Stem Cells Labeled with Nanoparticles for Treating Liver Cirrhosis

J Clin Transl Hepatol. 2023 Apr 28;11(2):382-392. doi: 10.14218/JCTH.2021.00580. Epub 2022 May 27.

Authors

Feng-Yong Liu^{1

2

3}, Ming Shi², Xin Li³, Hong-Jun Yuan³, Xiao-Mei Tian^{1

3}, Yi-Mao Xia^{1

3}, Min Zhou⁴, Fu-Sheng Wang^{1

2}

Affiliations

¹ Chinese PLA Medical School, Beijing, China.
² Senior Department of Infectious Diseases, Fifth Medical Center of PLA General Hospital, Beijing, China.
³ Department of Interventional Radiology, Senior Department of Oncology, Fifth Medical Center of PLA General Hospital, Beijing, China.
⁴ Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Abstract

Background and aims: Stem cell transplantation is a potential treatment option for liver cirrhosis (LC). Accurately and noninvasively monitoring the distribution, migration, and prognosis of transplanted stem cells using imaging methods is important for in-depth study of the treatment mechanisms. Our study aimed to develop Au-Fe₃O₄ silica nanoparticles (NPs) as tracking nanoplatforms for dual-modal stem cell imaging.

Methods: Au-Fe₃O₄ silica NPs were synthesized by seed-mediated growth method and co-precipitation. The efficiency and cytotoxicity of the NPs-labeled bone marrow-derived mesenchymal stem cells (BM-MSCs) were evaluated by Cell Counting Kit-8 assays, ICP-MS, phenotypic characterization, and histological staining. The biodistribution of labeled BM-MSCs injected through different routes (the hepatic artery or tail vein) into rats with LC was detected by magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and Prussian blue staining.

Results: Synthesized Au-Fe₃O₄ silica NPs consisted of a core (star-shaped Au NPs) and an outside silica layer doped with Fe₃O₄ NPs. After 24 h coincubation with 2.0 OD concentration of NPs, the viability of BM-MSCs was 77.91%±5.86% and the uptake of Au and Fe were (22.65±1.82) µg/mL and (234.03±11.47) µg/mL, respectively. The surface markers of labeled BM-MSCs unchanged significantly. Labeled BM-MSCs have osteogenic and adipogenic differentiation potential. Post injection in vivo, rat livers were hypointense on MRI and hyperintense on PAI. Prussian blue staining showed that more labeled BM-MSCs accumulated in the liver of the hepatic artery group. The severity of LC of the rats in the hepatic artery group was significantly alleviated.

Conclusions: Au-Fe₃O₄ silica NPs were suitable MRI/PAI dual-modal imaging nanoplatforms for stem cell tracking in regenerative medicine. Transhepatic arterial infusion of BM-MSCs was the optimal route for the treatment of LC.

Keywords: Bone marrow-derived mesenchymal stem cells; Dual-modal imaging; Liver cirrhosis; Nanoparticles; Stem cell tracking.