Hao-Hao Wang

Durable Mesenchymal Stem Cell Labelling by Using Polyhedral Superparamagnetic Iron Oxide Nanoparticles

Small polyhedral superparamagnetic iron oxide (SPIO) nanoparticles (<10 nm) coated with a thin layer of silica were prepared (SPIO@SiO(2) and SPIO@SiO(2)-NH(2)). Surface modification of the small polyhedral silica-coated SPIO nanoparticles with amines led to substantially higher mesenchymal stem cell (MSC) labelling efficiency without the use of additional transfecting agents. Therefore, amine surface-modified nanoparticles (SPIO@ SiO(2)-NH(2)) appeared to be the preferred candidate for MSC labelling. In vitro studies demonstrated that controlled labelling of SPIO@SiO(2) and SPIO@SiO(2)-NH(2) did not cause MSC death or proliferation inhibition. MSCs labelled with SPIO@SiO(2)-NH(2) nanoparticles retained differentiation potential and showed osteogenic, adipogenic and chondrogenic differentiations. The noncytotoxic polyhedral SPIO@SiO(2)-NH(2) nanoparticle-labelled MSCs were successfully implanted in rabbit brain and erector spinae muscle, and demonstrated long-lasting, durable MRI labelling efficacy after 8-12 weeks.

Biological and Magnetic Contrast Evaluation of Shape-Selective Mn–Fe Nanowires

One-dimensional composite Mn-Fe oxide nanostructures of different sizes (nanoneedles, nanorods, and nanowires) were prepared by a linker-induced organization of manganese-doped iron oxide nanoparticles. The nanostructures were obtained by the treatment of MnFe2O4 nanoparticles in the presence of cystamine. The average lengths of nanoneedle, nanorod, and nanowire are approximately 400, 800, and 1000 nm, respectively. High-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray (EDX) spectroscopy, and inductively coupled plasma-optical emission spectroscopy (ICP-OES) were employed to characterize the morphologies and the elemental contents of the nanostructures. As an example of their potential applications, these nanostructures were explored as the cell-labeling agents for magnetic resonance imaging (MRI). The magnetic contrast properties of the nanostructures were characterized by a 1.5 T (Tesla) whole body MR system. 10 mug/mL of the nanostructures caused substantial negative contrast. After in vitro incubation, the nanostructures could be effectively incorporated into the cells of a monocyte/macrophage cell line (RAW264.7). These cellspsila viability and proliferation potential were not affected when the labeling concentration was less than 50 mug/mL.

Efficacy and Durability in Direct Labeling of Mesenchymal Stem Cells Using Ultrasmall Superparamagnetic Iron Oxide Nanoparticles with Organosilica, Dextran, and PEG Coatings

We herein report a comparative study of mesenchymal stem cell (MSC) labeling using spherical superparamagnetic iron oxide (SPIO) nanoparticles containing different coatings, namely, organosilica, dextran, and poly(ethylene glycol) (PEG). These nanomaterials possess a similar SPIO core size of 6–7 nm. Together with their coatings, the overall sizes are 10–15 nm for all SPIO@SiO2, SPIO@dextran, and SPIO@PEG nanoparticles. These nanoparticles were investigated for their efficacies to be uptaken by rabbit bone marrow-derived MSCs without any transfecting agent. Experimentally, both SPIO@SiO2 and SPIO@PEG nanoparticles could be successfully uptaken by MSCs while the SPIO@dextran nanoparticles demonstrated limited labeling efficiency. The labeling durability of SPIO@SiO2 and SPIO@PEG nanoparticles in MSCs after three weeks of culture were compared by Prussian blue staining tests. SPIO@SiO2 nanoparticles demonstrated more blue staining than SPIO@PEG nanoparticles, rendering them better materials for MSCs labeling by direct uptake when durable intracellullar retention of SPIO is desired.

Low‐intensity pulsed ultrasound increases cellular uptake of superparamagnetic iron oxide nanomaterial: Results from human osteosarcoma cell line U2OS

To determine whether low‐intensity pulsed ultrasound (LIPUS) is able to facilitate the uptake of a superparamagnetic iron oxide (SPIO) nanomaterial by cells that do not express high endocytosis capacity.

Mesenchymal stem cell intracellular labeling using silica-coated superparamagnetic iron oxide nanoparticles with amine functional peripheries

Two types of superparamagnetic iron oxide nanoparticles designed for mesenchymal stem cell labeling and magnetic resonance imaging in vivo tracking were constructed in our laboratories. Both types of nanoparticles have an iron oxide core and a thin layer of silica coating, one of them has additional surface modification with amine. The overall particle size was around 8 nanometers. The in vitro study results demonstrated that, without the application of a transfection agent, both nanoparticles could be incorporated into bone marrow derived mesenchymal stem cells and located in lysosomes. Surface modification with amine significantly increased mesenchymal stem cell labeling efficiency, leading to an increased magnetic resonance imaging detection sensitivity of 2-5 folds.

Pitfalls in interpreting rat knee joint magnetic resonance images and their histological correlation.

Background: Magnetic resonance (MR) imaging has been increasingly used as an investigational tool for assessing the structure and function of animal joint disease models, while to date MR tomographic knowledge of laboratory animal skeletal microanatomy remains limited. Purpose: To describe pitfalls in interpreting rat knee joint MR images and their histological correlation. Material and Methods: MR scans of the right knee of five 3-month-old Sprague-Dawley (SD) rats were carried out using a 4.7T magnet, using a fat-suppressed three-dimensional (3D) gradient echo sequence with a spatial resolution of 59×117×234 µm. Histology assessment with hematoxylin and eosin staining and Safranin O staining was carried out in the five 3-month-old SD rats and two SD rats of 1 month and 6 months old, respectively. MR images were analyzed by a radiologist, and histology data were assessed by a radiologist and a pathologist. Results: Though the MR images were acquired in normal rats, many signs unfamiliar to radiologists were noted, including notch-like bright signal areas in the epiphysis, gray signal areas in the epiphysis, and fuzzy joint surface of the epiphysis of the femur and tibia. Detailed inspection of the histology specimen showed more unfamiliar features of rat knee microanatomy, including curvy or dipped surface of the femur/tibia epiphysis, areas composed of a mixture of cartilage and bone components, normal notch structure, cyst-like structure, and cavity between cortical lamellae under the joint cartilage. Conclusion: There are a number of normal microstructures of the rat knee joint that can be potentially misinterpreted as arthritic changes on MR images. Recognizing these rat knee microstructures can help correct image reading during biomedical research.

Fossa Trochanterica of the Proximal Femur in Rabbits: An Anatomic Structure for Potential Misinterpretation on Magnetic Resonance Images

Background: Magnetic resonance imaging (MRI) has been increasingly used as an investigational tool for assessing the structure and function of animal skeletal disease models. However, to date, MRI tomographic knowledge of laboratory animal skeletal anatomy and pathology remains limited. Purpose: To demonstrate that fossa trochanterica of the proximal femur in rabbits can potentially be misinterpreted as a bone lesion on MR images. Material and Methods: Twenty 28–30-week-old male New Zealand white rabbits were used in the study. Corticosteroid-induced osteonecrosis induction was carried out with a combined administration of lipopolysaccharide and methylprednisolone. In this animal model, it is known that osteonecrosis commonly occurs in the proximal femur. MRI at 1.5T was performed before osteonecrosis induction, and at 1 and 2 weeks post-osteonecrosis induction. For anatomical imaging of the proximal femur, coronal sectional images were obtained to align the femoral head, neck, and proximal shaft in a single plane. Volumetric computed tomography (CT) comprised continuous axial acquisitions through the bilateral hip joints and femurs and was performed on one age- and sex-matched New Zealand white rabbit to correlate MRI anatomical findings. Results: In 30% of the acquired normal data sets, a low-signal area surrounded by high-signal bone marrow was observed slightly distal to the femoral head and medial to the third trochanter. This dark, low-signal area resembled an osteonecrosis lesion on MR images. Volumetric CT clarified that the low MR signal was due to the deep fossa trochanterica structure in the rabbit proximal femur. Conclusion: Improved understanding of the cross-sectional anatomy of the fossa trochanterica in the rabbit proximal femur will prevent misinterpretation as a bone lesion on MR images.

Novel one-dimensional Mn—Fe oxide nanowires for cell labeling and magnetic resonance imaging

Novel one-dimensional Mn-Fe oxide nanowires, which were prepared by a ligand-induced self-organization of Mn-Fe oxide nanoparticles, were employed as contrast agents for magnetic resonance imaging and cell labeling. The magnetic properties of the nanowires were characterized by a 1.5 Tesla whole body magnetic resonance imaging (MRI) machine, which revealed a substantial change in MRI signal at particle concentration of 100 mug/mL, and considerably change in MRI signal at particle concentration of 10 mug/mL. After incubation in vitro, the nanowires were effectively incorporated into the macrophage cells.