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Biomimetic method produces large numbers of MRI-trackable mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are among the major stem cells used for cell therapy and regenerative medicine. In-vivo cell-tracking by magnetic resonance imaging (MRI) is crucial for regenerative medicine, allowing verification that the transplanted cells reach the targeted sites.  However, the results from trials using stem cells have proved problematic due to varying results and inadequate tracking systems.  Now, researchers led by Carnegie Mellon University have developed a new biomimetic method for preparing mesenchymal stem cells (MSCs) that leads to the production of more native stem cells and labels them with an FDA-approved iron-oxide nanoparticle, known as ferumoxytol. The team state that their technology could allow researchers to track the cells in vivo using MRI during preclinical and clinical trials. The opensource study is published by Scientific Reports.

Previous studies show that clinical trials using MSCs have presented mixed results, with some patients reacting well and others not responding to the stem cell treatment. To understand why these results can be so variable, researchers need to be able to track the stem cells as they migrate through the body. It has been hypothesized that stem cells could be labelled with a superparamagnetic iron-oxide (SPIO) contrast agent and image the patient using MRI.  Ferumoxytol is the only SPIO nanoparticle that has been approved by the FDA, however, researchers have been unable to label MSCs with ferumoxytol in cell culture without the help of a transfection agent, which can change the cells’ biology and inhibit their effectiveness. Furthermore, researchers have had difficulty culturing the large amount of cells needed for clinical dosing with current methods producing cells of different sizes and functionalities.  The current study takes advantage of the cell’s natural ability to engulf and internalize ferumoxytol in vivo, using a bio-mimicry method to create an environment in a petri dish that is much like the environment found inside the body.

The current study developed a new way to culture MSCs by introducing other cells from the bone marrow, mimicking the in-vivo environment. Results show that MSCs retain their optimal size and regeneration capabilities and can internalize ferumoxytol for cell-tracking. Data findings show that as MSCs are multi-potent, this new methodology can prepare more native cells for applications in cell therapy and regenerative medicine.

Results show that the biomimetic method can recover phagocytic activity of cultured MSCs, so that MSCs can be labelled by ferumoxytol after cell culture and expansion, with no need of transfection agents and/or electroporation.  Data findings show that this biomimetic ‘in-vivo’ environment can re-size the cultured MSCs and that the resized small and round MSCs show greater phagocytosis of ferumoxytol than large and flat MSCs.

The team surmise that their new bio-mimicry method makes use of the in-vivo environment of MSCs to prepare native MSCs, so that the phagocytic activity of cultured MSCs can be recovered.  They go on to add that, in turn, the expanded MSCs can then be labelled with ferumoxytol, which is currently the only FDA-approved SPIO nanoparticle for humans.  For the future, the researchers state that it is hoped their method could allow cell-tracking by MRI in both pre-clinical and clinical studies.

Source: Scientific Reports

 

Bio-mimicry” method can increase the labeling of MSCs by Ferumoxytol and decrease size of MSCs on day 7 of culture.  (A) Prussian blue staining of MSCs after Ferumoxytol labeling through the “bio-mimicry” method. Red arrows are pointing Prussian blue negative cells. (B) Prussian blue staining of MSCs from the “bio-mimicry” labeling method, but absence of Ferumoxytol. Summary of iron concentration.  A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI.  Ho et al 2016.
Bio-mimicry” method can increase the labeling of MSCs by Ferumoxytol and decrease size of MSCs on day 7 of culture. (A) Prussian blue staining of MSCs after Ferumoxytol labeling through the “bio-mimicry” method. Red arrows are pointing Prussian blue negative cells. (B) Prussian blue staining of MSCs from the “bio-mimicry” labeling method, but absence of Ferumoxytol. Summary of iron concentration. A New Method for Preparing Mesenchymal Stem Cells and Labeling with Ferumoxytol for Cell Tracking by MRI. Ho et al 2016.

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