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 1

Department of Radiology, University of California San Francisco, UCSF Medical Center, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Academic Radiology (Impact Factor: 1.75). 04/2005; 12(4):502-10. DOI: 10.1016/j.acra.2004.12.021
Source: PubMed


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.

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Available from: Robert A J Oostendorp, Aug 25, 2015
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    • "We found that, after transplantation of UCMSCs, the function of the ovary recovered. Previous study has shown that UCMSCs transplanted by intravenous migrate into several organs after hours [32]. And the ovulation of mice needs 4 days, so we chose after one week to measure the UCMSC location and function. "
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    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(5976):690491. DOI:10.1155/2013/690491
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    • "In our case, after 24 h of incubation, we noticed contrast agent uptake that resulted in detection on qualitative imaging; however, even better results were obtained with much lower incubation times when protamine was added. Other transfection agents such as lipofectin or poly-L-lysine (PLL) can be used to expedite labeling with great success [39, 40]. However, unlike protamine, most uptake-enhancing agents are not approved by health authorities and as such will have limited usefulness for cell tracking applications in humans. "
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    ABSTRACT: To develop and characterize a clinically applicable, fast and efficient method for stem cell labeling with ferucarbotran and protamine for depiction with clinical MRI. The hydrodynamic diameter, zeta potential and relaxivities of ferucarbotran and varying concentrations of protamine were measured. Once the optimized ratio was found, human mesenchymal stem cells (MSCs) were labeled at varying incubation times (1-24 h). Viability was assessed via Trypan blue exclusion testing. 150,000 labeled cells in Ficoll solution were imaged with T1-, T2- and T2*-weighted sequences at 3 T, and relaxation rates were calculated. Varying the concentrations of protamine allows for easy modification of the physicochemical properties. Simple incubation with ferucarbotran alone resulted in efficient labeling after 24 h of incubation while assisted labeling with protamine resulted in similar results after only 1 h. Cell viability remained unaffected. R2 and R2* relaxation rates were drastically increased. Electron microscopy confirmed intracellular iron oxide uptake in lysosomes. Relaxation times correlated with results from ICP-AES. Our results show internalization of ferucarbotran can be accelerated in MSCs with protamine, an approved heparin antagonist and potentially clinically applicable uptake-enhancing agent.
    European Radiology 09/2009; 20(3):640-8. DOI:10.1007/s00330-009-1585-1 · 4.01 Impact Factor
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