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Overcoming the barriers to umbilical cord blood transplantation.Primary Author: Susan Staba KellyPrimary Author: Department of Pediatrics.Date Published: 2010 03 03Abstract: Abstract Umbilical cord blood (UCB) transplantation (UCBT) has seen a marked increase in utilization in recent years, especially in the pediatric population; however, graft failure, delayed engraftment and profound delay in immune reconstitution leads to significant morbidity and mortality in adults. The lack of cells available for post-transplant therapies, such as donor lymphocyte infusions, has also been considered a disadvantage. To overcome the cell-dose barrier, the combination of two UCB units is becoming commonplace in adolescent and adult populations, and is currently being studied in pediatrics as well. In some studies, the use of two UCB units appears to have a positive impact on outcomes; however, engraftment is still suboptimal. A possible additional way to improve outcome and extend applicability of UCBT is via ex vivo expansion. Studies to develop optimal expansion conditions are still in the exploratory phase; however, recent studies suggest expanded UCB is safe and can improve outcomes. The ability to transplant across HLA disparities, rapid procurement time and decreased graft-versus-host disease (GvHD) seen with UCBT makes it a promising stem cell source and, while barriers exist, consistent progress is being made to overcome them.
Organochlorine pesticides in umbilical cord blood serum of women from Southern Spain and adherence to the Mediterranean diet.Primary Author: M Mariscal-ArcasPrimary Author: Department of Nutrition and Food Science, University of Granada, Spain.Date Published: 2010 3 8Abstract: Exposure of pregnant women to organochlorine (OC) pesticides largely derives from contaminated food, but environmental, occupational, and domestic factors have also been implicated. We investigated the presence of nine OC residues in the umbilical cord blood of newborns in Southern Spain and analyzed the relationship of this exposure with maternal and pregnancy variables, including maternal adherence to the Mediterranean Diet (MD). OCs were detected in 95% of umbilical cord blood samples from the 318 mothers, who had a mean degree of adherence to the MD of 56.77 (SD: 16.35) (range, 0-100). The MD prioritizes consumption of vegetable and fruit over meat and dairy products, and OCs are generally lipophilic molecules that accumulate in foods of animal origin. Consumption of meat, fish, and dairy products was associated with dichlorodiphenyldichloroethylene (DDE) in umbilical cord serum, and dairy product intake with lindane. Vegetable consumption was also associated with lindane and fruit intake with endosulfan I. We found no significant association between MD adherence and the presence of OC residues in serum. However, closer adherence to the MD may offer greater protection against OC exposure because of its reduced content in meat and dairy products.
Optimization of magnetosonoporation for stem cell labeling.Primary Author: Daohai XiePrimary Author: Image-Guided Bio-Molecular Interventions Section, Department of Radiology, University of Washington School of Medicine, Seattle, USA.Date Published: 2010 3 9Abstract: Recent advances in magnetic cell labeling have taken place with the development of a magnetosonoporation (MSP) technique. The aim of this study was to optimize the MSP protocol in order to achieve high cell viability and intracellular uptake of MR contrast agents. First, we determined the sub-optimal MSP parameters by evaluating the viabilities of C17.2 neural stem cells without Feridex using various MSP intensities ranging from 0.1 to 1 w/cm(2), duty cycles at 20%, 50% or 100%, and exposure times from 1-15 min. The sub-optimized MSP parameters with cell viabilities greater than 90% were further optimized by evaluating both cell viability and intracellular iron uptake when Feridex was used. We then used the optimized MSP parameters to determinate the optimal concentration of Feridex for magnetic cell labeling. Subsequently, we validated the feasibility of using MRI to track the migration of neural stem cells from the transplanted sites to glioma masses in four mouse brains when the cells had been labeled with Feridex using the optimized MSP protocol. The MRI findings were confirmed by histological correlations. In vitro experiments demonstrated that the optimal MSP protocol was achieved at 20% duty cycle, 0.3 w/cm(2) ultrasound intensity, 5-min exposure time and 1mg/mL Feridex. This study demonstrated that the optimized MSP cell labeling technique can achieve both high cell viability and intracellular uptake of MR contrast agents, and has the potential to be a useful cell labeling technique to facilitate future clinical translation of MRI-integrated cell therapy. Copyright (c) 2010 John Wiley & Sons, Ltd.
Microsphere size effects on embryoid body incorporation and embryonic stem cell differentiation.Primary Author: Richard L CarpenedoPrimary Author: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, Georgia.Date Published: 2010 3 9Abstract: Differentiation of pluripotent embryonic stem cells (ESCs) in vitro via multicellular spheroids called embryoid bodies (EBs) is commonly performed to model aspects of early mammalian development and initiate differentiation of cells for regenerative medicine technologies. However, the three-dimensional nature of EBs poses unique challenges for directed ESC differentiation, including limited diffusion into EBs of morphogenic molecules capable of specifying cell fate. Degradable polymer microspheres incorporated within EBs can present morphogenic molecules to ESCs in a spatiotemporally controlled manner to more efficiently direct differentiation. In this study, the effect of microsphere size on incorporation into EBs and ESC differentiation in response to microsphere- mediated morphogen delivery were assessed. PLGA microspheres with mean diameters of 1, 3, or 11 mum were fabricated and mixed with ESCs during EB formation. Smaller microspheres were incorporated more efficiently throughout EBs than larger microspheres, and regardless of size, retained for at least 10 days of differentiation. Retinoic acid release from incorporated microspheres induced EB cavitation in a size-dependent manner, with smaller microspheres triggering accelerated and more complete cavitation than larger particles. These results demonstrate that engineering the size of microsphere delivery vehicles incorporated within stem cell environments can be used to modulate the course of differentiation. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
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