Comparison of iron oxide labeling properties of hematopoietic progenitor cells from umbilical cord blood and from peripheral blood for subsequent in vivo tracking in a xenotransplant mouse model XXX.
ABSTRACT To compare and optimize ferumoxides labeling of human hematopoietic progenitor cells from umbilical cord blood and from peripheral blood for subsequent in vivo tracking with a clinical 1.5 T MR scanner.
Human hematopoietic progenitor cells, derived from umbilical cord blood or peripheral blood, were labeled with Ferumoxides by simple incubation or lipofection. Cellular iron uptake was quantified with spectrometry. Then, 3 x 10(7)-labeled cells were injected into the tail vein of 12 female nude Balb/c mice. The mice underwent magnetic resonance imaging before and 24 hours after injection. Precontrast and postcontrast signal intensities of liver, spleen, and bone marrow were measured and tested for significant differences with the t-test. Immunostains served as a histopathologic standard of reference.
After labeling by simple incubation, only umbilical cord blood cells, but not peripheral blood cells, showed a significant iron uptake and could be tracked in vivo with magnetic resonance imaging. Using lipofection, both cell types could be tracked in vivo. A significant decline in signal intensity was observed in liver, spleen, and bone marrow at 24 hours after injection of efficiently labeled ferumoxides cells (P < .05). Histopathology proved the distribution of iron oxide-labeled cells to these organs.
Hematopoietic progenitor cells from umbilical cord blood can be labeled by simple incubation with an Food and Drug Administration-approved magnetic resonance contrast agent with sufficient efficiency to provide an in vivo cell tracking at 1.5 T. Progenitor cells from peripheral blood need to be labeled with adjunctive transfection techniques to be depicted in vivo at 1.5 T.
[Show abstract] [Hide abstract]
ABSTRACT: Mesoporous silica nanoparticles (MSNs) are used in drug delivery and cell tracking applications. As Mn(2+) is already implemented as a "positive" cell contrast agent in preclinical imaging procedures (in the form of MnCl2 for neurological studies), the introduction of Mn in the porous network of MSNs would allow labelling cells and tracking them using MRI. These particles are in general internalized in endosomes, an acidic environment with high saline concentration. In addition, the available MSN porosity could also serve as a carrier to deliver medical/therapeutic substances through the labelled cells. In the present study, manganese oxide was introduced in the porous network of MCM-48 silica nanoparticles (Mn-M48SNs). The particles exhibit a narrow size distribution (∼140 nm diam.) and high porosity (∼60% vol.), which was validated after insertion of Mn. The resulting Mn-M48SNs were characterized by TEM, N2 physisorption, and XRD. Evidence was found with H2-TPR, and XPS characterization, that Mn(ii) is the main oxidation state of the paramagnetic species after suspension in water, most probably in the form of Mn-OOH. The colloidal stability as a function of time was confirmed by DLS in water, acetate buffer and cell culture medium. In NMR data, no significant evidence of Mn(2+) leaching was found in Mn-M48SNs in acidic water (pH 6), up to 96 hours after suspension. High longitudinal relaxivity values of r1 = 8.4 mM(-1) s(-1) were measured at 60 MHz and 37 °C, with the lowest relaxometric ratios (r2/r1 = 2) reported to date for a Mn-MSN system. Leukaemia cells (P388) were labelled with Mn-M48SNs and nanoparticle cell internalization was confirmed by TEM. Finally, MRI contrast enhancement provided by cell labelling with escalated incubation concentrations of Mn-M48SNs was quantified at 1 T. This study confirmed the possibility of efficiently confining Mn into M48SNs using incipient wetness, while maintaining an open porosity and relatively high pore volume. Because these Mn-labelled M48SNs express strong "positive" contrast media properties at low concentrations, they are potentially applicable for cell tracking and drug delivery methodologies.Nanoscale 10/2013; 5(23). DOI:10.1039/c3nr02969g · 6.74 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Mesenchymal stem cells, which are poorly immunogenic and have potent immunosuppressive activities, have emerged as promising cellular therapeutics for the treatment of several diseases. Mesenchymal-like cells derived from Wharton's Jelly, called umbilical cord matrix stem cells (UCMSCs), reportedly secrete a variety of cytokines and growth factors, acting as trophic suppliers. Here, we used UCMSCs to treat premature ovarian failure (POF). Ovarian function was evaluated by ovulation and the number of follicles. Apoptosis of the granulosa cells (GC) was analyzed by TUNEL staining. We found that after transplantation of the UCMSCs, apoptosis of cumulus cells in the ovarian damage model was reduced and the function of the ovary had been recovered. The sex hormone level was significantly elevated in mice treated with UCMSCs. The number of follicles in the treated group was higher than in the control group. Our results demonstrate that UCMSCs can effectively restore ovary functionality and reduce apoptosis of granulosa cells. We compared the RNA expression of the UCMSCs treated group with the POF model and wild-type control group and found that the UCMSC group is most similar to the wild-type group. Our experiments provide new information regarding the treatment of ovarian function failure.08/2013; 2013:690491. DOI:10.1155/2013/690491
[Show abstract] [Hide abstract]
ABSTRACT: Tracking the fate of cells after infusion would be a valuable asset for many stem cell therapies, but very few (cell) labels are approved for human therapeutic use. Superparamagnetic iron oxide particles (SPIO) can be internalized into stem cells in vitro to allow real-time tracking with gradient echo magnetic resonance imaging, but SPIO are approved for (diagnostic) imaging and not for (therapeutic) cell labeling in vivo. In this study, we investigated the possibility of labeling stem cells with an SPIO approved for patient use, albeit in a novel manner by enhancing uptake with the use of a transfection agent, also approved for patient use. Although there are many reports of hematopoietic stem cells being labeled with SPIO, there is some controversy regarding the efficiency of this and whether undifferentiated CD34+ progenitor (stem) cells are able to take up iron in the absence of a transfection agent to enhance the process. Human CD34+ cells were treated in vitro as follows: incubation with (i) medium only (control), (ii) ferumoxide (Endorem) and (iii) ferumoxide (Endorem) plus exposure to a transfection agent (protamine sulfate). Cells were incubated for 2, 4 and 24 hours and assessed for viability, differentiation capacity and visualized in vitro with 3-T magnetic resonance imaging. The cells were also analyzed by means of flow cytometry and morphology examined by electron microscopy. CD34+ hematopoietic progenitor cells can internalize ferumoxide (Endorem) independently of a transfection agent. However, uptake of ferumoxide is enhanced after exposure to protamine sulfate. Iron labeling of CD34+ cells in this manner does not affect cell viability and does not appear to affect the potential of the cells to grow in culture. Iron-labeled CD34+ cells can be visualized in vitro on 3-T magnetic resonance image scanning. Endorem and protamine sulfate can be combined to promote iron oxide nanoparticle uptake by CD34+ cells, and this methodology can potentially be used to track the fate of cells in a clinical trial setting because both compounds are (separately) approved for clinical use.Cytotherapy 03/2013; 15(3):384-90. DOI:10.1016/j.jcyt.2012.10.016 · 3.10 Impact Factor