Cardiovascular disease remains a prevalent problem in the U.S., resulting in death as well as disability. Stem cell therapy has emerged as a promising approach to treating ischemic cardiomyopathy, but its success has been limited by a low rate of stem cell retention and engraftment due to “wash out” of the cells by blood flow and perpetual muscular contraction. To overcome this problem, investigators at North Carolina State University attached stem cells to magnetic nanoparticles and utilized magnetic targeting to increase the efficiency of cell retention in the heart.
Magnetic targeting of FDA-approved nanoparticles
Feraheme® (ferumoxytol) consists of iron oxide nanoparticles coated with carbohydrate and is FDA-approved for the treatment of anemia in adults. Previous work has shown that Feraheme® particles can attach a number of stem cell types in the presence of heparin and protamine. Based on these findings, researchers labeled the particles with human cardiosphere-derived stem cells (CDCs). Cytotoxicity assays – based on a number of factors including cell viability, apoptosis, and proliferation – revealed that FHP labeling did not have any toxic effects on human CDCs. What’s more, the ability of the cells to differentiate was not affected.
Subsequent in vivo testing using rat CDCs found little to no inflammation associated with intravenous injection of the nanocomplexes into the rat subjects, as noted by the lack of macrophage clustering. Three weeks after particle introduction, rats subjected to magnetic targeting of the nanocomplexes showed a significant and marked improvement in heart morphology.
Using a rat model, researchers were able to show that clinically approved iron oxide particles could be used to bind human CDCs in the presence of heparin and protamine, without any toxic effects to the cells. In addition, they showed that magnetic targeting of the resulting nanocomplexes increases retention and engraftment of stem cells in the heart, enhancing their therapeutic efficacy.
While there are still some details to be worked out, such as the safe maximum dosage and the development of equipment compatible with patient care, the translation of this approach to the clinical setting should be assisted by the inclusion of FDA-approved magnetic nanoparticles and stem cells already in use. The approach is not limited to cardiosphere-derived stem cells, but could also be utilized to increase retention of other stem cell types. A detailed report of the findings can be found in “Biomaterials.”
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