11 research outputs found
Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation
PURPOSE: To determine whether intravenous ferumoxytol can be used to effectively label mesenchymal stem cells (MSCs) in vivo and can be used for tracking of stem cell transplants. MATERIALS AND METHODS: This study was approved by the institutional animal care and use committee. Sprague-Dawley rats (6–8 weeks old) were injected with ferumoxytol 48 hours prior to extraction of MSCs from bone marrow. Ferumoxytol uptake by these MSCs was evaluated with fluorescence, confocal, and electron microscopy and compared with results of traditional ex vivo–labeling procedures. The in vivo–labeled cells were subsequently transplanted in osteochondral defects of 14 knees of seven athymic rats and were evaluated with magnetic resonance (MR) imaging up to 4 weeks after transplantation. T2 relaxation times of in vivo–labeled MSC transplants and unlabeled control transplants were compared by using t tests. MR data were correlated with histopathologic results. RESULTS: In vivo–labeled MSCs demonstrated significantly higher ferumoxytol uptake compared with ex vivo–labeled cells. With electron microscopy, iron oxide nanoparticles were localized in secondary lysosomes. In vivo–labeled cells demonstrated significant T2 shortening effects in vitro and in vivo when they were compared with unlabeled control cells (T2 in vivo, 15.4 vs 24.4 msec; P < .05) and could be tracked in osteochondral defects for 4 weeks. Histologic examination confirmed the presence of iron in labeled transplants and defect remodeling. CONCLUSION: Intravenous ferumoxytol can be used to effectively label MSCs in vivo and can be used for tracking of stem cell transplants with MR imaging. This method eliminates risks of contamination and biologic alteration of MSCs associated with ex vivo–labeling procedures. © RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130858/-/DC
The Epigenome at the Crossroad Between Social Factors, Inflammation, and Osteoporosis Risk
Both genetic and environmental factors are involved
in the pathogenesis of osteoporosis and other skeletal
disorders. Epidemiological studies have revealed an influence
of a variety of social factors, including socioeconomic status
(SES) on the risk of osteoporosis. The mechanisms involved
are complex and still incompletely elucidated. Nevertheless, a
variety of clinical risk factors known to influence skeletal
homeostasis have been reported as being socially patterned,
including nutrition, exercise, and other lifestyles, among
others. These factors may impact the skeleton through a variety
of mechanisms. Among them, there is increasing evidence
for a role of DNA methylation and other epigenetic mechanisms.
Indeed, several studies of human cohorts and experimental
models showed that social deprivation is associated
with changes in the methylation pattern of a number of genes,
including some involved in stress and inflammatory responses.
The influence of socioeconomic factors may be important
not only during postnatal life but also in utero and may
be transmitted to future generations by its direct effect on
peripheral and target tissues and perhaps through epigenetic
inheritance. Although the exact relevance of these pathways in
humans has not been fully elucidated yet, they bring attention
to the influences of social factors on the skeletal health of the
individuals and their descendants. Therefore, they also bring
forward our responsibility for both present and future
generations