| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Experimental Studies |
1 From the Experimental Neuroimaging Section, Laboratory of Diagnostic Radiology Research, National Institutes of Health, 10 Center Dr, Rm B1N256, Bethesda, MD 20892. Received September 23, 2002; revision requested December 3; final revision received February 14, 2003; accepted March 12. Address correspondence to A.S.A. (e-mail: saali@cc.nih.gov).
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
|---|
MATERIALS AND METHODS: PLL was incubated with ferumoxides for 60 minutes, incompletely coating the superparamagnetic iron oxide (SPIO) through electrostatic interactions. Cells were coincubated overnight with the ferumoxides-PLL complex, and iron uptake, cell viability, apoptosis indexes, and reactive oxygen species formation were evaluated. The disappearance or the life span of the detectable iron nanoparticles in cells was also evaluated. The iron concentrations in the media also were assessed at different time points. Data were expressed as the mean ± 1 SD, and one-way analysis of variance and the unpaired Student t test were used to test for significant differences.
RESULTS: Intracytoplasmic nanoparticles were stained with Prussian blue when the ferumoxides-PLL complex had magnetically labeled the human mesenchymal stem and HeLa cells. The long-term viability, growth rate, and apoptotic indexes of the labeled cells were unaffected by the endosomal incorporation of SPIO, as compared with these characteristics of the nonlabeled cells. In nondividing human mesenchymal stem cells, endosomal iron nanoparticles could be detected after 7 weeks; however, in rapidly dividing cells, intracellular iron had disappeared by five to eight divisions. A nonsignificant transient increase in reactive oxygen species production was seen in the human mesenchymal stem and HeLa cell lines. Labeled human mesenchymal stem cells did not differentiate to other lineage. A significant increase in iron concentration was observed in both the human mesenchymal stem and HeLa cell media at day 7.
CONCLUSION: Magnetic cellular labeling with the ferumoxides-PLL complex had no short- or long-term toxic effects on tumor or stem cells.
© RSNA, 2003
Index terms: Cell labeling • Contrast media, experimental studies • Experimental study • Iron • Magnetic resonance (MR), contrast media, **.121432 • Radiobiology, cell and tissue studies
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
|---|
After intravenous injection, most SPIO nanoparticles accumulate in the Kupffer cells in the liver and in the reticuloendothelial system in the spleen (5,6). Ultrasmall SPIO nanoparticles are used as blood-pool imaging agents and for imaging the lymphatic system. Ultrasmall SPIOs have a long intravascular half-life and are taken up by the reticuloendothelial system and tissue macrophages. Dextran-coated iron oxide nanoparticles are biodegradable and metabolized by cells. Subsequently, the iron is introduced into the normal plasma iron pool and can be incorporated into the hemoglobin of red cells or used for other metabolic processes (7). Dendrimer-coated SPIOs (ie, magnetodendrimers) have been used for cellular labeling, and the labeled cells were shown to be viable at 10 days after labeling (8).
More recently, cross-linked monocrystalline iron oxide nanoparticles attached to a short human immunodeficiency virus–transactivator transcription peptide have also been used to label cells for in vivo MR tracking (9,10). However, to our knowledge, the long-term viability of cells labeled with cross-linked monocrystalline iron oxide nanoparticles attached to a short human immunodeficiency virus–transactivator transcription peptide has not been described.
Stem cells and other mammalian cells are being considered for use in repairing or replacing damaged organs, improving tissue function, or other therapeutic approaches (ie, genetically engineered cells) (11–15). Paramagnetic or modified dextran-coated SPIOs have been used to label cells ex vivo, providing researchers with the ability to monitor the migration of these cells with MR imaging (9,10,16). The migration of magnetically labeled progenitor oligodendrocytes following implantation into the lateral ventricles of dysmyelinated rats was identified in vivo by using MR imaging up to 6 weeks following transplantation (8).
Mammalian stem cells can be efficiently labeled with a U.S. Food and Drug Administration (FDA)–approved contrast agent, ferumoxides, combined with different nonviral transfection agents, such as poly-L-lysine (PLL). These cells can then be used for cellular MR imaging (17,18). Heohn et al (19) labeled mouse embryonic stem cells with ultrasmall SPIOs by using the transfection agent Fugene (Roche Diagnostic, Indianapolis, Ind), and they used this agent in a stroke model to track the cells with MR imaging.
The introduction of ferumoxides-PLL complexes into cells may increase the formation of reactive oxygen species and hydroxyl-free radicals. This phenomenon, in turn, may alter cell metabolism or increase the rate of apoptosis or cell death (3,4). Although other SPIO or ultrasmall SPIO particles that are used for cellular labeling have not demonstrated any adverse effects in short-term studies of cell viability and differentiation, the long-term follow-up findings of cells labeled with SPIO have not been evaluated (8).
The purpose of this study was to evaluate the effect of using the ferumoxides-PLL complex for magnetic cell labeling on the long-term viability, function, metabolism, and iron utilization of mammalian cells.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
|---|
Cell Cultures
Human mesenchymal stem cells (BioWhittaker, Walkersville, Md) and human cervical carcinoma cells—specifically, HeLa cells (National Cancer Institute, National Institutes of Health, Bethesda, Md)—were grown in standard culture media at 37°C and in a 95% air per 5% CO2 atmosphere. Human mesenchymal stem cells and HeLa cells were grown to confluence in a 75-cm2 culture flask. Media were replaced every 4 days.
Cell Labeling
The polyamine PLL hydrobromide (molecular weight, 388,100 d; cell culture grade, catalog number P1524) (Sigma, St Louis, Mo) was used as the transfection agent. A stock solution of PLL (1.5 mg/mL) was added to the culture media at a dilution of 1:1,000 and mixed with ferumoxides (50 µg/mL) for 60 minutes at room temperature on a rotating shaker. These culture media containing the ferumoxides-PLL complex were added to the cells such that the final concentration of ferumoxides was 25 µg/mL and the final dilution of PLL was 1:2,000. The cell cultures were kept overnight at 37°C in a 95% air per 5% CO2 atmosphere.
Histologic Analysis
After being incubated overnight (ie, >12 hours) with the ferumoxides-PLL complex, the cells were washed two times to remove excess contrast agent, collected after trypsinization, and transferred to cytospin slides. For Prussian blue staining, which indicates the presence of iron, the cells were fixed with 4% glutaraldehyde, washed, incubated for 30 minutes with 2% potassium ferrocyanide (ie, Perl reagent) in 6% hydrochloric acid, washed again, and counterstained with nuclear fast red. For diaminobenzide-enhanced Prussian Blue staining, the slides were reacted with activated 0.014% diaminobenzide (containing 0.03% hydrogen peroxide) for 10–15 minutes, washed three times with phosphate-buffered saline (PBS), and then counterstained with nuclear fast red or Gill hematoxylin.
Cellular Viability, Metabolism, and Apoptosis
The viability of ferumoxides-PLL–labeled human mesenchymal stem and HeLa cells was evaluated by using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay (Roche Molecular Biochemicals, Indianapolis, Ind). The mesenchymal stem cells were grown in 96-well plates at 5 x 103 cells per well and the HeLa cells were grown in 24-well plates at 2 x 104 cells per well. Cells in 50% of the wells of both cell types were labeled with the ferumoxides-PLL complex overnight. The remaining cells, which were not labeled with the complex and served as control cells, were kept under identical conditions.
The magnetically labeled and nonlabeled cells were maintained by replacing the media every 4 days. After cells were labeled and washed two times with PBS, MTT was added at a final concentration of 0.5 mg of medium per milliliter. Then, both the labeled and control cells were incubated for 4 hours at 37°C in a 5% CO2 atmosphere. An equal volume of solubilizer buffer was then added, according to manufacturer (Roche Molecular Biochemicals) recommendations, and the cells were incubated overnight at 37°C in a 5% CO2 atmosphere. The absorbance of the formazen product was then measured at a wavelength of 570 nm, with 750 nm as the (subtracted) reference wavelength.
For assessment of ROS, cells were grown to confluence in 25-cm2 flasks. After the media were changed, the cells were incubated overnight with media containing the ferumoxides-PLL complex or with media only (control). The cells were then washed two times with PBS and incubated in fresh culture media. The magnetically labeled and nonlabeled cells were maintained under identical conditions, and ROS assays were performed and apoptosis rates were determined at various time intervals. For the ROS assay, the cells were collected after trypsinization, washed twice with PBS, and resuspended in 1 mL of PBS at 1 x 106 cells/mL. The intracellular formation of ROS was detected by using the fluorescent probe CM-H2DCFDA (Molecular Probes, Eugene, Ore). CM-H2DCFDA is a nonfluorescent agent that forms fluorescent esters when it is reacted with ROS inside cells. CM-H2DCFDA was added at a final concentration of 10 µmol/L, and the cells were incubated for 60 minutes at 37°C.
For determination of the number of cells undergoing apoptosis, the cells were collected after trypsinization, washed twice with ice-cold PBS, and resuspended in 1 mL of annexin medium (Vybrant Apoptosis Assay Kit 2; Molecular Probes) at 1 x 106 cells/mL. Ten microliters of fluorescent-labeled annexin medium was added to 100 µL of cell suspension, which was then kept at room temperature for 15–20 minutes. The cells were then washed twice with annexin medium and placed on fluorescent plates for fluorescent reading.
To perform ROS assays and determine apoptosis rates, the fluorescence was analyzed in a fluorescent plate reader (LS-55 Fluorescent Plate Reader; PerkinElmer Life Sciences, Fremont, Calif) by using a 490–500-nm wavelength for excitation and a 525-nm wavelength for emission. The values were normalized to the values obtained from nonlabeled HeLa and human mesenchymal stem cells. The percentages of dead cells and cells undergoing apoptosis were determined by using a flow cytometer (Becton Dickinson, San Jose, Calif). Labeled and nonlabeled HeLa and mesenchymal stem cells were incubated with 10 µL of annexin medium and 2 µL of propidium iodide at room temperature for 15–20 minutes, and flow cytometry was performed by using a fluorescent-activated cell sorter (Becton Dickinson).
Monitoring Iron Concentration in Dividing and Nondividing Cells
HeLa cells were grown to confluence in 75-cm2 flasks, and they were incubated overnight with media only or media containing the ferumoxides-PLL complex, washed two times with PBS, and then incubated in fresh culture media. Mesenchymal stem cells were grown to confluence in multiple 150-cm2 flasks, and they were incubated with media only or media containing the ferumoxides-PLL complex. The cells were then washed two times with PBS and incubated in fresh culture media.
Three million nonlabeled and labeled cells were collected, centrifuged and resuspended homogeneously in 0.5 mL of 8% gelatin at 60°C, and then chilled at 3°C to allow the suspensions to solidify for nuclear MR relaxometry, MR imaging, and quantification of the average iron concentration per cell. Tubes containing the cells suspended in gelatin were kept at 4°C until further study. The cells were also collected at regular intervals for Prussian blue staining. To determine if the intracellular iron was being released into the media from the ferumoxides-PLL labeled cells, 3 mL of media from the labeled and nonlabeled cells grown in culture for 7 days was collected weekly for 5 weeks and refrigerated at 4°C. Cell viability was determined weekly by means of trypan blue dye exclusion assay of both the labeled and nonlabeled cells.
To monitor the iron concentration in dividing cells, two million labeled and nonlabeled HeLa cells were separately transferred to 75-cm2 flasks in fresh media and allowed to propagate for a week. Three million cells were collected every 7 days for 5 weeks, and propagation studies were performed. The doubling times of the labeled and nonlabeled HeLa cells were assessed. To monitor the presence of intracytoplasmic iron in confluent growth– inhibited mesenchymal stem cells, three million cells were collected at regular intervals for nuclear MR relaxometry and to determine the average iron concentration per cell. Confluent cell cultures were maintained by replacing the media every 7 days.
Nuclear MR Relaxometry
Nuclear MR relaxometry was performed to assess the cellular uptake of the ferumoxides-PLL complex. The 1/T2 values for gelatin suspensions of ferumoxides-PLL–labeled cells and nonlabeled cells were compared by using a 1.0-T custom-designed nuclear MR relaxometer at 23°C. 1/T2 values were determined by using a Carr-Purcell-Meiboom-Gill pulse sequence with 500 echoes and interecho times of 1 and 5 milliseconds.
MR Imaging
MR imaging of cells suspended in gelatin was performed at 1.5 T (Signa; GE Medical Systems, Milwaukee, Wis) by using a 5-inch surface coil. MR imaging was performed by using a fast spin-echo sequence (3,000/45 [repetition time msec/echo time msec], echo train length of eight) and a multisection gradient-echo sequence (300/20, 20° flip angle). The MR images were obtained by using a matrix size of 256 x 160, two acquired signals, a section thickness of 2 mm, and a 6–8-cm field of view. The signal intensities of the nonlabeled and ferumoxides-PLL–labeled cells were determined from a circular 35-mm2 region of interest. The percentage change in signal intensity (
SI) due to labeling was defined as follows: SI = [(SIL - SIU)/SIU] · 100% (1), where SIL is the signal intensity of the ferumoxides-PLL–labeled cells and SIU is the signal intensity of the nonlabeled cells. Measurements of regions of interest were performed by one author (B.K.L.), and signal intensity changes were analyzed by two authors (J.A.F., A.S.A.) in consensus.
Quantification of Iron in Cells and Media
The iron content of the labeled cells was assessed by using a ferrozin-based spectrophotometric assay (Shimadzu UV-1601; Shimadzu, Columbia, Md) and nuclear MR relaxometry, as previously described (9). The average iron content per cell, expressed in mean values ± SDs, was determined by calculating the mean values determined with nuclear MR relaxometry and ferrozin assays divided by the number of cells in each sample. To determine the iron concentration in the media, the media were dried overnight at 110°C and then digested with 500 µL of a mixture of perchloric acid and nitric acid (3:1 ratio) at 60°C in a heating block. The iron concentration was then assessed by using nuclear MR relaxometry, as previously described (8,18).
Statistical Analysis
All data are expressed as means ± 1 SD. Values for viability and ROS production in labeled cells were expressed as the percentage of the average value in the corresponding control cells. The unpaired Student t test was applied to identify significant differences between the labeled and corresponding control (ie, nonlabeled) cells at different time points. To identify significant differences in the iron content of the cells and media at different time points for the labeled and nonlabeled cells, one-way analysis of variance followed by a post hoc Fisher protected least-significant-difference test was applied. P less than .05 was considered to indicate a significant difference.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
|---|
|
|
|
|
|
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
|---|
Although free cationic iron that may be chelated by citrate or other negatively charged intracellular molecules could not be detected in the magnetically labeled cells (data not shown), the transient increases in ROS production and formazen by-product level may have been due to free cationic iron in the cytoplasm outside of the endosome. To our knowledge, there have been no reports demonstrating the exact pathway of the biotransformation of nanoparticulate forms of iron to its cationic forms in the cell. However, there is a report (7) describing the biodegradation of iron nanoparticles and their incorporation into the hemoglobin of erythrocytes; these findings indicate that the iron can be released from the cell and become available for iron metabolic pathways.
Intracellular iron homeostasis is a delicate balance between the synthesis of intracellular ferritin molecules and the synthesis of transferrin receptors (4). When there is increased iron in the cytoplasm, ferritin synthesis is stimulated and free iron is taken up into the ferritin molecules (4), thereby decreasing the toxic effect of free iron. The results of the current study indicate that no oxidative injury or possible sublethal injury occurs within the cells in association with either ferumoxides-PLL cell labeling or the presence of dextran-coated iron oxide nanoparticles in the endosomes. A similar cellular safety profile has been observed by other investigators who labeled cells with SPIO (8–10).
The results of the MTT assay performed in our study, which reflect the activity of electron transport (metabolic activity), indicate that the elevation in MTT observed in labeled HeLa cells, as compared with the concentration of MTT in nonlabeled HeLa cells, may be due to the availability of additional free iron in the cells, which can be used to increase cellular metabolic activity. In another experiment, we found that exact numbers of ferumoxides-labeled cells had higher concentrations of formazen by-product than did nonlabeled cells (data not shown).
The ability to detect MR imaging signal intensity alterations originating from a population of labeled cells intermixed with native (ie, nonlabeled) cells is dependent on the labeling efficiency of the ferumoxides-PLL complex, the labeling conditions, the cell division, or the elimination of iron resulting from the recirculation of the endosome to the cell surface or the incorporation of the iron into metabolic pathways. Depending on the goals or the types of studies planned, it may be advantageous or disadvantageous to have iron remaining in the labeled cells following infusion or implantation of cells into tissue. MR imaging can depict loss of intracellular iron particles in rapidly dividing cells, especially with use of T2*-weighted techniques. However, cells that are not dividing because they are either dormant owing to confluence when in vitro or in the G0 resting state when in vivo or terminally differentiated may retain the iron oxide nanoparticles in endosomes and therefore be visible for longer periods at MR imaging.
Loss of magnetic labeling through metabolism or dilution (ie, cell division) would be desirable if the primary goal were to infuse or transplant stem cells into damaged tissue, because the loss of labeling would translate into less magnetic susceptibility effect for the cells and lengthening of the T2* of the tissue or organ (ie, the T2* would approach that of native, normal, or repaired tissue). Therefore, loss of magnetic labeling would allow the application of other imaging techniques, such as magnetization transfer imaging, T1 or T2 maps, diffusion imaging, or MR spectroscopy, to further characterize the differentiation of tissue repair or replacement.
Conversely, if the goal of the study were to monitor the temporal-spatial dynamics of labeled cells infused intravenously or implanted into tissue, then cells that either do not divide or undergo a limited number of divisions would be desirable. The depiction of slow metabolism or slow disappearance of the endosomal iron on T2*-weighted MR images following transplantation may be important to track cells or determine if more cells are needed as part of cellular therapy. Once the appropriate numbers of cells incorporate to the location(s), however, it may be desirable for cells to metabolize or eliminate the iron to allow subsequent characterization of the area of interest by using other MR imaging techniques.
The increased iron concentration in the media observed following ferumoxides-PLL cell labeling may have been due to iron release during cell division, exocytosis, or the release of iron from dead cells. The exact form of these iron particles in the cell culture media samples was not determined, but it is unlikely that the iron would remain in solution as nanoparticles. Reports have shown that within a lysosome or endosome (ie, low pH) environment, ferromagnetic particles become solubilized in a few days (20). There are also reports describing tissue macrophages and mononuclear cells phagocytosing the nanoparticles after intravenous injection of ultrasmall SPIO (21,22). The phagocytosis of iron particles from dead or alive magnetically labeled cells may pose a problem in the in vivo tracking of the labeled cells. However, it is unlikely that the iron particles released from labeled cells immediately after intravenous administration of labeled cells would be a problem because any SPIO released into the blood would be taken up by the reticuloendothelial system of the liver and spleen.
The observed disappearance of the major portion of the dextran-coated iron particles plus PLL from the rapidly dividing cells was due to dilution following cellular division or metabolism. However, exocytosis might have played a major role in the release of iron from the cells. In nondividing cells, exocytosis and metabolism are the major pathways for the disappearance of iron from cells.
Practical applications: Magnetic cellular labeling with the FDA-approved dextran-coated SPIO contrast agent ferumoxides plus the transfection agent PLL caused no short- or long-term toxic effects in the mammalian cells. The cell viability and rates of apoptosis in the labeled cells did not change over time, as compared with these features of the nonlabeled cells. Although there may be trace amounts of biodegradable iron released from the cells, most of the iron particle remains intact in the endosome. The disappearance of iron from the cell is mostly due to dilution through cellular division. Magnetic labeling of stem cells and other mammalian cells is safe and may facilitate the ability to perform cellular MR imaging to monitor the migration of cells in vivo following their transplantation or intravenous administration.
|
FOOTNOTES |
|---|
See also Science to Practice in this issue.
Abbreviations: FDA = Food and Drug Administration, MTT = 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, PBS = phosphate-buffered saline, PLL = poly-L-lysine, ROS = reactive oxygen species, SPIO = superparamagnetic iron oxide
Author contributions: Guarantors of integrity of entire study, A.S.A., B.R.M., J.A.F.; study concepts and design, all authors; literature research, A.S.A., L.A.B., J.A.F.; experimental studies, A.S.A., B.R.M., L.A.B., B.K.L., H.K.; data acquisition, A.S.A., B.K.L., L.A.B.; data analysis/interpretation, A.S.A., B.R.M., L.A.B., J.A.F.; statistical analysis, A.S.A., J.A.F.; manuscript preparation, A.S.A., L.A.B., H.K., B.K.L., J.A.F.; manuscript definition of intellectual content, A.S.A., B.R.M., L.A.B., E.K.J., J.A.F.; manuscript editing, B.R.M., L.A.B., E.K.J., B.K.L., H.K., J.A.F.; manuscript revision/review, A.S.A., J.A.F.; manuscript final version approval, all authors
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTS DISCUSSIONREFERENCES |
|---|
Related Article
This article has been cited by other articles:
|
|
 |
|
  M. Neri, C. Maderna, C. Cavazzin, V. Deidda-Vigoriti, L. S. Politi, G. Scotti, P. Marzola, A. Sbarbati, A. L. Vescovi, and A. Gritti Efficient In Vitro Labeling of Human Neural Precursor Cells with Superparamagnetic Iron Oxide Particles: Relevance for In Vivo Cell Tracking Stem Cells, February 1, 2008; 26(2): 505 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Maxwell, J. Bonde, D. A. Hess, S. A. Hohm, R. Lahey, P. Zhou, M. H. Creer, D. Piwnica-Worms, and J. A. Nolta Fluorophore-Conjugated Iron Oxide Nanoparticle Labeling and Analysis of Engrafting Human Hematopoietic Stem Cells Stem Cells, February 1, 2008; 26(2): 517 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Ebert, D. G. Taylor, H.-L. Nguyen, D. P. Kodack, R. J. Beyers, Y. Xu, Z. Yang, and B. A. French Noninvasive Tracking of Cardiac Embryonic Stem Cells In Vivo Using Magnetic Resonance Imaging Techniques Stem Cells, November 1, 2007; 25(11): 2936 - 2944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. S. Politi, M. Bacigaluppi, E. Brambilla, M. Cadioli, A. Falini, G. Comi, G. Scotti, G. Martino, and S. Pluchino Magnetic Resonance-Based Tracking and Quantification of Intravenously Injected Neural Stem Cell Accumulation in the Brains of Mice with Experimental Multiple Sclerosis Stem Cells, October 1, 2007; 25(10): 2583 - 2592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Amsalem, Y. Mardor, M. S. Feinberg, N. Landa, L. Miller, D. Daniels, A. Ocherashvilli, R. Holbova, O. Yosef, I. M. Barbash, et al. Iron-Oxide Labeling and Outcome of Transplanted Mesenchymal Stem Cells in the Infarcted Myocardium Circulation, September 11, 2007; 116(11_suppl): I-38 - I-45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schafer, R. Kehlbach, J. Wiskirchen, R. Bantleon, J. Pintaske, B. R. Brehm, A. Gerber, H. Wolburg, C. D. Claussen, and H. Northoff Transferrin Receptor Upregulation: In Vitro Labeling of Rat Mesenchymal Stem Cells with Superparamagnetic Iron Oxide Radiology, August 1, 2007; 244(2): 514 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. Rice, E. W. Hsu, H. Sheng, D. A. Evenson, A. J. Freemerman, K. M. Safford, J. M. Provenzale, D. S. Warner, and G. A. Johnson Superparamagnetic Iron Oxide Labeling and Transplantation of Adipose-Derived Stem Cells in Middle Cerebral Artery Occlusion-Injured Mice Am. J. Roentgenol., April 1, 2007; 188(4): 1101 - 1108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. L. Aranguren, A. Luttun, C. Clavel, C. Moreno, G. Abizanda, M. A. Barajas, B. Pelacho, M. Uriz, M. Arana, A. Echavarri, et al. In vitro and in vivo arterial differentiation of human multipotent adult progenitor cells Blood, March 15, 2007; 109(6): 2634 - 2642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vemulapalli, S. D. Metzler, G. Akabani, N. A. Petry, N. J. Niehaus, X. Liu, N. H. Patil, K. L. Greer, R. J. Jaszczak, R. E. Coleman, et al. Cell Therapy in Murine Atherosclerosis: In Vivo Imaging with High-Resolution Helical SPECT Radiology, January 1, 2007; 242(1): 198 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhu, L. Zhou, and F. XingWu Tracking Neural Stem Cells in Patients with Brain Trauma N. Engl. J. Med., November 30, 2006; 355(22): 2376 - 2378. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zhou, P. D. Acton, and V. A. Ferrari Imaging Stem Cells Implanted in Infarcted Myocardium J. Am. Coll. Cardiol., November 21, 2006; 48(10): 2094 - 2106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Agbulut, M. Mazo, C. Bressolle, M. Gutierrez, K. Azarnoush, L. Sabbah, N. Niederlander, G. Abizanda, E. J. Andreu, B. Pelacho, et al. Can bone marrow-derived multipotent adult progenitor cells regenerate infarcted myocardium? Cardiovasc Res, October 1, 2006; 72(1): 175 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Stuckey, C. A. Carr, E. Martin-Rendon, D. J. Tyler, C. Willmott, P. J. Cassidy, S. J.M. Hale, J. E. Schneider, L. Tatton, S. E. Harding, et al. Iron Particles for Noninvasive Monitoring of Bone Marrow Stromal Cell Engraftment into, and Isolation of Viable Engrafted Donor Cells from, the Heart Stem Cells, August 1, 2006; 24(8): 1968 - 1975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Y. Khakoo, S. Pati, S. A. Anderson, W. Reid, M. F. Elshal, I. I. Rovira, A. T. Nguyen, D. Malide, C. A. Combs, G. Hall, et al. Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma J. Exp. Med., May 15, 2006; 203(5): 1235 - 1247. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. L. Wu, Q. Ye, L. M. Foley, T. K. Hitchens, K. Sato, J. B. Williams, and C. Ho In situ labeling of immune cells with iron oxide particles: An approach to detect organ rejection by cellular MRI PNAS, February 7, 2006; 103(6): 1852 - 1857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Yocum, L. B. Wilson, P. Ashari, E. K. Jordan, J. A. Frank, and A. S. Arbab Effect of Human Stem Cells Labeled with Ferumoxides- Poly-L-lysine on Hematologic and Biochemical Measurements in Rats Radiology, May 1, 2005; 235(2): 547 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Matuszewski, T. Persigehl, A. Wall, W. Schwindt, B. Tombach, M. Fobker, C. Poremba, W. Ebert, W. Heindel, and C. Bremer Cell Tagging with Clinically Approved Iron Oxides: Feasibility and Effect of Lipofection, Particle Size, and Surface Coating on Labeling Efficiency Radiology, April 1, 2005; 235(1): 155 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Anderson, J. Glod, A. S. Arbab, M. Noel, P. Ashari, H. A. Fine, and J. A. Frank Noninvasive MR imaging of magnetically labeled stem cells to directly identify neovasculature in a glioma model Blood, January 1, 2005; 105(1): 420 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. M. Bulte, D. L. Kraitchman, A. M. Mackay, M. F. Pittenger, A. S. Arbab, G. T. Yocum, H. Kalish, E. K. Jordan, S. A. Anderson, A. Y. Khakoo, et al. Chondrogenic differentiation of mesenchymal stem cells is inhibited after magnetic labeling with ferumoxides Blood, November 15, 2004; 104(10): 3410 - 3413. [Full Text] [PDF]
|
|
|
|
|
|
|
