Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging

Thu, Mya; Bryant, L. Henry; Coppola, Tiziana; Jordan, Elaine; Budde, Matthew D.; Lewis, Bobbi K.; Chaudhry, Aneeka; Ren, Jiaqiang; Varma, Nadimpalli Ravi S.; Arbab, Ali S.; Frank, Joseph A.

doi:10.1038/nm.2666

Cited by 191 publications

(238 citation statements)

References 36 publications

Supporting

Mentioning

212

Contrasting

Order By: Relevance

“…The PFC-based cell labeling agent was designed and optimized specifically for clinical MRI. Prior clinical MRI cell tracking work (e.g., de Vries et al) (14) has relied on off-label use of metal-ion-based nanoparticles, often in conjunction with transfection agents (15). Historically, various PFC molecules have been contemplated for clinical use as artificial oxygen carriers (16) in large doses ($10 g/kg).…”

Section: Resultsmentioning

confidence: 99%

Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine‐19 MRI

Ahrens

Helfer

O'Hanlon

et al. 2014

Magnetic Resonance in Med

View full text Add to dashboard Cite

Purpose Cellular therapeutics are emerging as a treatment option for a host of serious human diseases. To accelerate clinical translation, noninvasive imaging of cell grafts in clinical trials can potentially be used to assess the initial delivery and behavior of cells. Methods The use of a perfluorocarbon (PFC) tracer agent for clinical fluorine‐19 (19F) MRI cell detection is described. This technology was used to detect immunotherapeutic dendritic cells (DCs) delivered to colorectal adenocarcinoma patients. Autologous DC vaccines were labeled with a PFC MRI agent ex vivo. Patients received DCs intradermally, and 19F spin‐density‐weighted MRI at 3 Tesla (T) was used to observe cells. Results Spin‐density‐weighted 19F images at the injection site displayed DCs as background‐free “hot‐spot” images. 19F images were acquired in clinically relevant scan times (<10 min). Apparent DC numbers could be quantified in two patients from the 19F hot‐spots and were observed to decrease by ∼50% at injection site by 24 h. From 3T phantom studies, the sensitivity limit for DC detection is estimated to be on the order of ∼105 cells/voxel in this study. Conclusion These results help to establish a clinically applicable means to track a broad range of cell types used in cell therapy. Magn Reson Med 72:1696–1701, 2014. © 2014 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance.

show abstract

Section: Resultsmentioning

confidence: 99%

Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine‐19 MRI

Ahrens

Helfer

O'Hanlon

et al. 2014

Magnetic Resonance in Med

View full text Add to dashboard Cite

show abstract

“…Recent studies, however, have shown that iron oxide labeling, combined with magnetic targeting, might improve graft retention in the rat heart [29,30,34,36]. Thus, ferumoxytol cell labeling might have utility in both in vivo cardiac graft imaging and cell retention.…”

Section: Mri Of Labeled Hesc-cpcs In the Pig Heart ©Alphamed Press 2016mentioning

confidence: 99%

“…Ferumoxytol interacts with cells via a synthetic carbohydrate coating and is currently used for the treatment of iron-deficiency anemia in the presence of chronic kidney disease [32]. Furthermore, ferumoxytol displays limited cytotoxicity and genotoxicity and might improve the viability of certain cell populations (i.e., microglia) [14,33,34].…”

Section: Introductionmentioning

confidence: 99%

Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

Skelton

Khoja

Almeida

et al. 2015

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Given the limited regenerative capacity of the heart, cellular therapy with stem cell-derived cardiac cells could be a potential treatment for patients with heart disease. However, reliable imaging techniques to longitudinally assess engraftment of the transplanted cells are scant. To address this issue, we used ferumoxytol as a labeling agent of human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) to facilitate tracking by magnetic resonance imaging (MRI) in a large animal model. Differentiating hESCs were exposed to ferumoxytol at different time points and varying concentrations. We determined that treatment with ferumoxytol at 300 mg/ml on day 0 of cardiac differentiation offered adequate cell viability and signal intensity for MRI detection without compromising further differentiation into definitive cardiac lineages. Labeled hESC-CPCs were transplanted by open surgical methods into the left ventricular free wall of uninjured pig hearts and imaged both ex vivo and in vivo. Comprehensive T 2 *-weighted images were obtained immediately after transplantation and 40 days later before termination. The localization and dispersion of labeled cells could be effectively imaged and tracked at days 0 and 40 by MRI. Thus, under the described conditions, ferumoxytol can be used as a long-term, differentiation-neutral cell-labeling agent to track transplanted hESC-CPCs in vivo using MRI. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:67-74 SIGNIFICANCEThe development of a safe and reproducible in vivo imaging technique to track the fate of transplanted human embryonic stem cell-derived cardiac progenitor cells (hESC-CPCs) is a necessary step to clinical translation. An iron oxide nanoparticle (ferumoxytol)-based approach was used for cell labeling and subsequent in vivo magnetic resonance imaging monitoring of hESC-CPCs transplanted into uninjured pig hearts. The present results demonstrate the use of ferumoxytol labeling and imaging techniques in tracking the location and dispersion of cell grafts, highlighting its utility in future cardiac stem cell therapy trials.

show abstract

“…Transplanted stem cells can be assessed for long-term periods using noninvasive imaging techniques [66,67]. Stem cells can be tracked in vivo after their transplantation using different strategies: initial labeling of stem cells with fluorescent dyes or magnetic nanoparticles, such as superparamagnetic iron oxide, and stem cell transfection with several reporter genes such as the LacZ and green fluorescence protein (GFP) [68,69]. The visualization of the labeled stem cells requires either simple, or complex and sophisticated imaging systems such as MRI [66,70,71], computed tomography imaging [72], PET and single-photon emission computed tomography imaging [73].…”

Section: Nanomedicine: a Giant Leap Forward In Disease Diagnosis And Trmentioning

confidence: 99%

“…Superparamagnetic iron oxide nanoparticles (60-150 nm in diameter) are composed of biodegradable and recyclable iron and are coated with dextran or carboxydextran to prevent aggregation and ensure aqueous solubility [74,75]. Magnetic nanoparticles can attach to the stem cell surface, but are also capable of being internalized by phagocytosis or, more often, by endocytosis [76], a process that is often facilitated by the use of coating and membrane receptor-binding agents [69,77]. Endocytosis of magnetic nanoparticles does not affect stem cell viability, growth, fate or differentiation [78].…”

Section: Nanomedicine: a Giant Leap Forward In Disease Diagnosis And Trmentioning

confidence: 99%

Nanodentistry: Combining Nanostructured Materials and Stem Cells for Dental Tissue Regeneration

2012

View full text Add to dashboard Cite

Regenerative dentistry represents an attractive multidisciplinary therapeutic approach that complements traditional restorative/surgery techniques and benefits from recent advances in stem cell biology, molecular biology, genomics and proteomics. Materials science is important in such advances to move regenerative dentistry from the laboratory to the clinic. The design of novel nanostructured materials, such as biomimetic matrices and scaffolds for controlling cell fate and differentiation, and nanoparticles for diagnostics, imaging and targeted treatment, is needed. The combination of nanotechnology, which allows the creation of sophisticated materials with exquisite fine structural detail, and stem cell biology turns out to be increasingly useful in regenerative medicine. The administration to patients of dynamic biological agents comprising stem cells, bioactive scaffolds and/or nanoparticles will certainly increase the regenerative impact of dental pathological tissues. This overview briefly describes some of the actual benefits and future possibilities of nanomaterials in the emerging field of stem cell-based regenerative dentistry.

show abstract

Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging

Cited by 191 publications

References 36 publications

Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine‐19 MRI

Clinical cell therapy imaging using a perfluorocarbon tracer and fluorine‐19 MRI

Magnetic Resonance Imaging of Iron Oxide-Labeled Human Embryonic Stem Cell-Derived Cardiac Progenitors

Nanodentistry: Combining Nanostructured Materials and Stem Cells for Dental Tissue Regeneration

Contact Info

Product

Resources

About