Iron Oxide Nanoparticles in Regenerative Medicine

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Stem cell technology may assist in the practice of regenerative medicine to replace unhealthy, nonfunctioning cells with new, viable cells. Embryonic stem cells are cultivated from donated human eggs that were fertilized or harvested from adult bone marrow cells[1]. This type of research may create treatments for a variety of degenerative diseases such as spinal injury, arthritis, diabetes, and heart disease[2]. Stem cells are also being used to control cell proliferation and differentiation in an effort to create anti-tumor treatments.  This research may lead to an ability to produce replacement organs or tissues, yet the nearer term objective is to develop practical techniques to observe and control the function of transplanted cells. Before becoming a viable, commonplace technology to treat degenerative diseases, several aspects of stem cell therapy have to be improved.  One such improvement is monitoring the behavior of and tracking of these cells within the body[3]. Magnetic resonance imaging (MRI) uses the distinct magnetic fields of an intravenously administered solution of gadolinium to enhance the clarity of images, allowing radiologists to better detect the presence of abnormalities or disease[4]. MRI provides higher resolution images than CT scans or X-rays without the risk of radiation[5].

Current contrast solutions do not provide the visibility needed to closely monitor the differentiation, renewal, apoptosis, and migration of stem cell implants. This challenge can be addressed by iron (III) oxide nanoparticles, which have uniform magnetic properties that are created by their atomic spin. That uniformity enables researchers to generate ultrasensitive molecular images[6]. Iron (III) oxide nanoparticles can also be modified in size from 5 to 45 nanometers, and below certain temperatures are ferromagnetic, meaning the nanoparticles align on an angle due to a magnetic force[7]. These seemingly simple manipulations of size and orientation allows for nanoparticles to be absorbed into a variety of cell types through endocytosis, and prevents interference of cell surface interactions[7]. Due to their flexibility in application and noninvasiveness, Fe2O3 nanoparticles have the potential to replace current gadolinium-based contracts. Advances in the observational potential of MRI’s in stem cells implants with the use of Fe2O3 will help researchers to better observe cell activity in vivo for research purposes and patient safety.

Stem cell stained with Prussian blue and counterstained with neutral red (A) Transmission-electron photomicrograph of stem cells (B).

(Source: Solanki et al., 2008) 

References

  1. "What Are Embryonic Stem Cells? [Stem Cell Information]." Stem Cell Basics. National Institutes of Health, U.S. Department of Health and Human Services, 13 Sept. 2010. Web. 20 Feb. 2015.
  2. Gutova, M., J. A. Frank, M. D'apuzzo, V. Khankaldyyan, M. M. Gilchrist, A. J. Annala, M. Z. Metz, Y. Abramyants, K. A. Herrmann, L. Y. Ghoda, J. Najbauer, C. E. Brown, M. S. Blanchard, M. S. Lesniak, S. U. Kim, M. E. Barish, K. S. Aboody, and R. A. Moats. "Magnetic Resonance Imaging Tracking of Ferumoxytol-Labeled Human Neural Stem Cells: Studies Leading to Clinical Use." Stem Cells Translational Medicine 2.10 (2013): 766-75. Web.
  3. "What are the Risks and Benefits of MRI." NPS MedicineWise. N.p., 23 May 2013. Web. 06 Feb. 2015.
  4. Liney, Gary. "Contrast Agents." MRI in Clinical Practice. London: Springer-Verlag, 2006. 13. Print.
  5. Solanki, Aniruddh, John D. Kim, and Ki-Bum Lee. "Nanotechnology for Regenerative Medicine: Nanomaterials for Stem Cell Imaging."Nanomedicine 3.4 (2008): 567-78. Web.
  6. "Stem Cells as Therapies." CALIFORNIA'S STEM CELL AGENCY. CALIFORNIA INSTITUTE FOR REGENERATIVE MEDICINE, 08 Sept. 2013. Web. 20 Feb. 2015.

References

  1. Citekey <span style="font-family: 'Trebuchet MS', 'Helvetica Neue', Arial, Helvetica, sans-serif; font-size: 14px; line-height: 21px; background-color: rgb(245, 245, 245);">What Are Embryonic Stem Cells? [Stem Cell Information] not found
  2. Citekey </span><span style="font-family: 'Trebuchet MS', 'Helvetica Neue', Arial, Helvetica, sans-serif; font-size: 14px; line-height: 21px; background-color: rgb(245, 245, 245);">What Are Embryonic Stem Cells? [Stem Cell Information] not found
  3. Citekey <span style="font-family: 'Trebuchet MS', 'Helvetica Neue', Arial, Helvetica, sans-serif; font-size: 14px; line-height: 21px; background-color: rgb(245, 245, 245);">10.5966/sctm.2013-0049 not found
  4. Citekey <span style="font-family: 'Trebuchet MS', 'Helvetica Neue', Arial, Helvetica, sans-serif; font-size: 14px; line-height: 21px; background-color: rgb(245, 245, 245);">What are the risks and benefits of MRI? not found
  5. Citekey <span style="font-family: 'Trebuchet MS', 'Helvetica Neue', Arial, Helvetica, sans-serif; font-size: 14px; line-height: 21px; background-color: rgb(245, 245, 245);">Contrast Agents not found
  6. Citekey <span style="font-family: 'Trebuchet MS', 'Helvetica Neue', Arial, Helvetica, sans-serif; font-size: 14px; line-height: 21px; background-color: rgb(245, 245, 245);">10.2217/17435889.3.4.567 not found
  7. Citekey </span><span style="font-family: 'Trebuchet MS', 'Helvetica Neue', Arial, Helvetica, sans-serif; font-size: 14px; line-height: 21px; background-color: rgb(245, 245, 245);">10.2217/17435889.3.4.567 not found

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Stem cell technology uses unspecialized cells originating from embryos or bone marrow to treat degenerative diseases and replace non-functioning organs or tissues. To commercialize this form of therapy, stem cell treatments must be made easier to monitor, track, and observe in vivo. Using MRI’s with Fe2O3 nanoparticles will enhance the contrast resolution in images and thus improve the range of application and increase the sensitivity of the images. This will allow technicians to better understand and control the cell-to-cell interactions of transplanted tissues with the higher resolution images.

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To improve solubility and stability of Fe2O3 in cells, polymer coatings such as dextran can be added to the outer surface of nanoparticles. These coatings allow for additional isotope and florescent labels to be attached, making the stem cells observable by optical, nuclear, and magnetic imaging. Additionally, Fe2O3 nanoparticles in the form of dendrites composites (branching, treelike polymers), act as transfecting agents (transfection being the process of introducing nucleic acids into cells) allowing for adsorption in a variety of animal cell types as well as human cells. Decreasing the amount of additional transfecting agents introduced to the cells lowers toxicity risks. 

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While further studies are needed to confirm causation, nanoparticles dissolved in cells may contribute to the formation of free hydroxyl radicals and reactive oxygen species, leading to apoptosis and altered cellular metabolism. Iron2+ ions also may increase toxicity, necessitating a gold coating on the nanoparticles to prevent rapid dissolution of the iron oxide nanoparticles into the endosomes of the cells, which aid in cellular uptake.

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