Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement

Abstract

As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd2O3) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd2O3 nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd2O3 nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd2O3 nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r1 and r2 at 1.5 T and 21°C, for Gd2O3 nanoparticles in different cell samples were 3.6–5.3 s-1 mM-1 and 9.6–17.2 s-1 mM-1, respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd2O3 nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd2O3 nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed.<p>funding agencies|Swedish Research Council| 621-2007-3810 621-2009-5148 521-2009-3423 |VINNOVA| 2009-00194 |Center in Nanoscience and Technology at LiTH (CeNano)||</p

Tracking and Quantification of Magnetically Labeled Stem Cells Using Magnetic Resonance Imaging

“…For example, Gd 2 O 3 nanoparticles were used to label and monitor hematopoietic cells. [19] Another study enabled monitoring of the anatomical migration and the survival period of transplanted stem cells by using gadolinium for up to 1 month. [20] They reported that gadolinium in the cells was rapidly eliminated from the site and excreted upon cell death, and endothelial progenitor cells transplanted into the femoral muscle of rats migrated distally through the knee after hind limb ischemia.…”

The Emerging Role of Nanotechnology in Cell and Organ Transplantation

“…As a result, a variety of nanoparticles and nanodevices have been created using a variety of materials including iron, carbon, gold, silica, and silicon [11]. Nanoparticles have been designed to serve multiple functions: drug delivery [12], receptor mediated targeting [13], environmentally-triggered release [14], thermal ablation [15], molecular imaging [16], and magnetism [17]. On the other hand, nano-fluidic systems and nano-membranes have been developed for the selective filtration of fluids [18], diagnoses [19], and sustained delivery of drugs [20].…”

Seeing Stem Cells at Work In Vivo

“…If dechelated, the gadolinium ion can be deposited in organs. Gadolinium has been used to label different types of stem cells, such as hematopoietic progenitor cells, monocytic cells, endothelial progenitor cells, and MSCs for cell tracking [25–27]. However the long-term presence of gadolinium in engrafted cells may affect cell function and hence the therapeutic benefit of cell therapy.…”