Poly (dopamine) coated superparamagnetic iron oxide nanocluster for noninvasive labeling, tracking, and targeted delivery of adipose tissue-derived stem cells.

Naishun Liao,Youshi Zheng,Fan Pan,Xiaolong Liu,Da Zhang,Jun Peng,Jiumao Lin,Yingchao Wang,Ming Wu,Jingfeng Liu,Zuanfang Li

doi:10.1038/srep18746

Abstract

Tracking and monitoring of cells in vivo after transplantation can provide crucial information for stem cell therapy. Magnetic resonance imaging (MRI) combined with contrast agents is believed to be an effective and non-invasive technique for cell tracking in living bodies. However, commercial superparamagnetic iron oxide nanoparticles (SPIONs) applied to label cells suffer from shortages such as potential toxicity, low labeling efficiency, and low contrast enhancing. Herein, the adipose tissue-derived stem cells (ADSCs) were efficiently labeled with SPIONs coated with poly (dopamine) (SPIONs cluster@PDA), without affecting their viability, proliferation, apoptosis, surface marker expression, as well as their self-renew ability and multi-differentiation potential. The labeled cells transplanted into the mice through tail intravenous injection exhibited a negative enhancement of the MRI signal in the damaged liver-induced by carbon tetrachloride, and subsequently these homed ADSCs with SPIONs cluster@PDA labeling exhibited excellent repair effects to the damaged liver. Moreover, the enhanced target-homing to tissue of interest and repair effects of SPIONs cluster@PDA-labeled ADSCs could be achieved by use of external magnetic field in the excisional skin wound mice model. Therefore, we provide a facile, safe, noninvasive and sensitive method for external magnetic field targeted delivery and MRI based tracking of transplanted cells in vivo.

Highlights

Resonance imaging (MRI)[11,12,13,14], have been used to track the stem cells after transplanting in vivo
We have succeeded in the synthesis of a core-shell nanocomposite of clusters of superparamagnetic iron oxide nanoparticles coated with poly (SPIONs clusters@PDA) as a highly sensitive and biocompatible magnetic resonance imaging (MRI) contrast for cancer cells[24]
We investigated the cell apoptosis of adipose tissue-derived stem cells (ADSCs) to further confirm the non-cytotoxicity of SPIONs cluster@PDA, which was determined by flow cytometry using Annexin-V-FITC/PI staining

Summary

Introduction

Resonance imaging (MRI)[11,12,13,14], have been used to track the stem cells after transplanting in vivo. The usage of FLI and BLI have been limited due to low tissue penetrating depth as well as photo attenuation and scattering[15,16]; on the other hand, both PET and SPECT have the disadvantage of being ionizing radiation[17] Among these imaging modalities, MRI is an ideal tool for stem cell tracking because of its inherent soft-tissue contrast, high perforated depth and non-ionizing radiation[11], and it has been successfully used for clinical evaluation of stem cell therapies[12,13]. In addition to the high MRI contrast enhancing ability, the SPIONs cluster@PDA nanocomposites have been demonstrated to respond rapidly to external magnetic field gradients in our previous work Followed by this advantage, we further established a mouse model of excisional skin wound to investigate the targeted guiding of cell homing to the wound by an external magnetic field and subsequently the curative effects of the SPIONs cluster@PDA labeled ADSCs

Methods

Results

Conclusion