Novel MRI Contrast from Magnetotactic Bacteria to Evaluate In Vivo Stem Cell Engraftment

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Abstract

Although human induced pluripotent stem cells (iPSCs) and their derivatives have great potential for the treatment of heart failure. The therapeutic benefit is limited by translational challenges of stem cells such as cell engraftment. Thus, a robust in vivo imaging technology is indispensable to advance the clinical implementation of stem cell therapy. While no available imaging technology meets the requirement for in vivo stem cell tracking, MRI is a highly promising tool due to its high spatial resolution, temporal resolution, and tissue contrast; yet, this modality lacks sensitivity. Superparamagnetic iron oxide particles (SPIONs) addresses this critical imaging issue and have been used as an MRI contrast agent for stem cell tracking. However, their critical limitation is the inability to evaluate cell viability as SPIONs remain in the tissue long after the death of transplanted cells. To address this shortcoming of SPIONs, the novel magneto-endosymbiont-based (MEs) contrast agent was developed (Magnelle®, Bell Biosystems, Inc., South SF, CA). The MEs utilize the magnetosome biosynthesized by magnetotactic bacteria (MTB), a specific intracellular structure containing inorganic magnetic iron crystals (magnetite or greigite). Having superparamagnetic property like SPIONs, MEs can be detected on T2* weighted imaging. MEs have high safety profile and do not interfere with the functions of transfected cells. Unlike SPIONs, the antiginecity of the MEs are readily recognized and removed from macrophages quickly after the death of labeled cells, eliminating signals from dead cells. In the previous study from our group, iPSC derived cardiomyocytes were labeled with MEs and detected successfully on MRI after transplantation into the heart. In vivo ME signals corresponded with luciferase-based bioluminescence imaging (BLI) of the transplanted cell viability. In conclusion, ME is a novel MRI contrast agent for in vivo cellular tracking that allows accurate longitudinal visualization of the engrafted cells.

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References

  1. 1.
    Thomson, J. A., et al. (1998). Embryonic stem cell lines derived from human blastocysts. Science, 282, 1145–1147.CrossRefGoogle Scholar
  2. 2.
    Takahashi, K., et al. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131, 861–872.CrossRefGoogle Scholar
  3. 3.
    Tanaka, A., Yuasa, S., Node, K., & Fukuda, K. (2015). Cardiovascular disease modeling using patient-specific induced pluripotent stem cells. International Journal of Molecular Sciences, 16, 18894–18922.CrossRefGoogle Scholar
  4. 4.
    Maehr, R., et al. (2009). Generation of pluripotent stem cells from patients with type 1 diabetes. Proceedings of the National Academy of Science U. S. A., 106, 15768–15773.CrossRefGoogle Scholar
  5. 5.
    Richard, J.-P., & Maragakis, N. J. (2015). Induced pluripotent stem cells from ALS patients for disease modeling. Brain Research, 1607, 15–25.CrossRefGoogle Scholar
  6. 6.
    Payne, N. L., et al. (2015). Application of human induced pluripotent stem cells for modeling and treating neurodegenerative diseases. New Biotechnology, 32, 212–228.CrossRefGoogle Scholar
  7. 7.
    Chidgey, A. P., Layton, D., Trounson, A., & Boyd, R. L. (2008). Tolerance strategies for stem-cell-based therapies. Nature, 453, 330–337.CrossRefGoogle Scholar
  8. 8.
    Jung, J.-H., Fu, X., & Yang, P. C. (2017). Exosomes generated from iPSC-derivatives: New direction for stem cell therapy in human heart diseases. Circulation Research, 120, 407–417.CrossRefGoogle Scholar
  9. 9.
    Hynes, B., et al. (2013). Potent endothelial progenitor cell-conditioned media-related anti-apoptotic, cardiotrophic, and pro-angiogenic effects post-myocardial infarction are mediated by insulin-like growth factor-1. European Heart Journal, 34, 782–789.CrossRefGoogle Scholar
  10. 10.
    Valina, C., et al. (2007). Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. European Heart Journal, 28, 2667–2677.CrossRefGoogle Scholar
  11. 11.
    Rota, M., et al. (2008). Local activation or implantation of cardiac progenitor cells rescues scarred infarcted myocardium improving cardiac function. Circulation Research, 103, 107–116.CrossRefGoogle Scholar
  12. 12.
    Hare, J. M., et al. (2009). A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. Journal of the American College of Cardiology, 54, 2277–2286.CrossRefGoogle Scholar
  13. 13.
    Kehat, I., et al. (2004). Electromechanical integration of cardiomyocytes derived from human embryonic stem cells. Nature Biotechnology, 22, 1282–1289.CrossRefGoogle Scholar
  14. 14.
    Sumi, T., Tsuneyoshi, N., Nakatsuji, N., & Suemori, H. (2008). Defining early lineage specification of human embryonic stem cells by the orchestrated balance of canonical Wnt/β-catenin, activin/nodal and BMP signaling. Development, 135, 2969–2979.CrossRefGoogle Scholar
  15. 15.
    Chong, J. J. H., et al. (2014). Human embryonic-stem-cell-derived cardiomyocytes regenerate non-human primate hearts. Nature, 510, 273–277.CrossRefGoogle Scholar
  16. 16.
    Mauritz, C., et al. (2008). Generation of functional murine cardiac myocytes from induced pluripotent stem cells. Circulation, 118, 507–517.CrossRefGoogle Scholar
  17. 17.
    Zhang, J., et al. (2009). Functional cardiomyocytes derived from human induced pluripotent stem cells. Circulation Research, 104, e30–e41.CrossRefGoogle Scholar
  18. 18.
    Passier, R., van Laake, L. W., & Mummery, C. L. (2008). Stem-cell-based therapy and lessons from the heart. Nature, 453, 322–329.CrossRefGoogle Scholar
  19. 19.
    Frangioni, J. V., & Hajjar, R. J. (2004). In vivo tracking of stem cells for clinical trials in cardiovascular disease. Circulation, 110, 3378–3383.CrossRefGoogle Scholar
  20. 20.
    Li, Z., et al. (2008). Comparison of reporter gene and iron particle labeling for tracking fate of human embryonic stem cells and differentiated endothelial cells in living subjects. Stem Cells (Dayton, Ohio), 26, 864–873.CrossRefGoogle Scholar
  21. 21.
    Parashurama, N., et al. (2016). Multimodality molecular imaging of cardiac cell transplantation: Part II. In vivo imaging of bone marrow stromal cells in swine with PET/CT and MR imaging. Radiology, 280, 826–836.CrossRefGoogle Scholar
  22. 22.
    Parashurama, N., et al. (2016). Multimodality molecular imaging of cardiac cell transplantation: Part I. Reporter gene design, characterization, and optical in vivo imaging of bone marrow stromal cells after myocardial infarction. Radiology, 280, 815–825.CrossRefGoogle Scholar
  23. 23.
    von der Haar, K., Lavrentieva, A., Stahl, F., Scheper, T., & Blume, C. (2015). Lost signature: Progress and failures in in vivo tracking of implanted stem cells. Applied Microbiology and Biotechnology, 99, 9907–9922.CrossRefGoogle Scholar
  24. 24.
    Lewin, M., et al. (2000). Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nature Biotechnology, 18, 410–414.CrossRefGoogle Scholar
  25. 25.
    Jasmin, et al. (2011). Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging. Journal of Nanobiotechnology, 9(4).CrossRefGoogle Scholar
  26. 26.
    Cunningham, C. H., et al. (2005). Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magnetic Resonance in Medicine, 53, 999–1005.CrossRefGoogle Scholar
  27. 27.
    Arai, T., et al. (2006). Dual in vivo magnetic resonance evaluation of magnetically labeled mouse embryonic stem cells and cardiac function at 1.5 t. Magnetic Resonance in Medicine, 55, 203–209.CrossRefGoogle Scholar
  28. 28.
    Dash, R., et al. (2011). Dual manganese-enhanced and delayed gadolinium-enhanced MRI detects myocardial border zone injury in a pig ischemia-reperfusion model. Circulation: Cardiovascular Imaging, 4, 574–582.Google Scholar
  29. 29.
    Hung, T.-C., et al. (2008). Multimodality evaluation of the viability of stem cells delivered into different zones of myocardial infarction. Circulation: Cardiovascular Imaging, 1, 6–13.Google Scholar
  30. 30.
    Nishida, K., et al. (2006). Magnetic targeting of bone marrow stromal cells into spinal cord: through cerebrospinal fluid. NeuroReport, 17, 1269–1272.CrossRefGoogle Scholar
  31. 31.
    Vandergriff, A. C., et al. (2014). Magnetic targeting of cardiosphere-derived stem cells with ferumoxytol nanoparticles for treating rats with myocardial infarction. Biomaterials, 35, 8528–8539.CrossRefGoogle Scholar
  32. 32.
    Uchida, M., et al. (2008). A human ferritin iron oxide nano-composite magnetic resonance contrast agent. Magnetic Resonance in Medicine, 60, 1073–1081.CrossRefGoogle Scholar
  33. 33.
    Nitz, W. R., & Reimer, P. (1999). Contrast mechanisms in MR imaging. European Radiology, 9, 1032–1046.CrossRefGoogle Scholar
  34. 34.
    Bos, C., et al. (2004). In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver. Radiology, 233, 781–789.CrossRefGoogle Scholar
  35. 35.
    Santoyo Salazar, J., et al. (2011). Magnetic iron oxide nanoparticles in 10–40 nm range: Composition in terms of magnetite/maghemite ratio and effect on the magnetic properties. Chemistry of Materials, 23, 1379–1386.CrossRefGoogle Scholar
  36. 36.
    Moraes, L., et al. (2012). Neuroprotective effects and magnetic resonance imaging of mesenchymal stem cells labeled with SPION in a rat model of Huntington’s disease. Stem Cell Research, 9, 143–155.CrossRefGoogle Scholar
  37. 37.
    Bull, E., et al. (2014). Stem cell tracking using iron oxide nanoparticles. International Journal of Nanomedicine, 9, 1641–1653.Google Scholar
  38. 38.
    Hillaireau, H., & Couvreur, P. (2009). Nanocarriers’ entry into the cell: Relevance to drug delivery. Cellular and Molecular Life Sciences CMLS, 66, 2873–2896.CrossRefGoogle Scholar
  39. 39.
    Cores, J., Caranasos, T. G., & Cheng, K. (2015). Magnetically targeted stem cell delivery for regenerative medicine. Journal of Functional Biomaterials, 6, 526–546.CrossRefGoogle Scholar
  40. 40.
    Suzuki, Y., et al. (2007). In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides. Magnetic Resonance in Medicine, 57, 1173–1179.CrossRefGoogle Scholar
  41. 41.
    Qiu, B., et al. (2010). Magnetosonoporation: instant magnetic labeling of stem cells. Magnetic Resonance in Medicine, 63, 1437–1441.CrossRefGoogle Scholar
  42. 42.
    Walczak, P., Kedziorek, D. A., Gilad, A. A., Lin, S., & Bulte, J. W. M. (2005). Instant MR labeling of stem cells using magnetoelectroporation. Magnetic Resonance in Medicine, 54, 769–774.CrossRefGoogle Scholar
  43. 43.
    Khurana, A., et al. (2013). Iron administration before stem cell harvest enables MR imaging tracking after transplantation. Radiology, 269, 186–197.CrossRefGoogle Scholar
  44. 44.
    Liu, L., et al. (2016). A new method for preparing mesenchymal stem cells and labeling with ferumoxytol for cell tracking by MRI. Scientific Reports, 6, 26271.CrossRefGoogle Scholar
  45. 45.
    Chen, J., et al. (2013). Guidance of stem cells to a target destination in vivo by magnetic nanoparticles in a magnetic field. ACS Applied Materials & Interfaces, 5, 5976–5985.CrossRefGoogle Scholar
  46. 46.
    Chung, J., et al. (2011). In vivo molecular MRI of cell survival and teratoma formation following embryonic stem cell transplantation into the injured murine myocardium. Magnetic Resonance in Medicine, 66, 1374–1381.CrossRefGoogle Scholar
  47. 47.
    Singh, N., Jenkins, G. J. S., Asadi, R., & Doak, S. H. (2010). Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION). Nano Reviews, 1.CrossRefGoogle Scholar
  48. 48.
    Elias, A., & Tsourkas, A. (2009). Imaging circulating cells and lymphoid tissues with iron oxide nanoparticles. Hematology American Society Hematology Education Program 720–726.  https://doi.org/10.1182/asheducation-2009.1.720.CrossRefGoogle Scholar
  49. 49.
    Chen, I. Y., et al. (2009). Comparison of optical bioluminescence reporter gene and superparamagnetic iron oxide MR contrast agent as cell markers for noninvasive imaging of cardiac cell transplantation. Molecular Imaging and Biology (MIB) Official Publication of the Academy of Molecular Imaging, 11, 178–187.CrossRefGoogle Scholar
  50. 50.
    Suzuki, Y., et al. (2008). In vivo serial evaluation of superparamagnetic iron-oxide labeled stem cells by off-resonance positive contrast. Magnetic Resonance in Medicine, 60, 1269–1275.CrossRefGoogle Scholar
  51. 51.
    Terrovitis, J., et al. (2008). Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival after transplantation in the heart. Circulation, 117, 1555–1562.CrossRefGoogle Scholar
  52. 52.
    Kim, J. A., Åberg, C., Salvati, A., & Dawson, K. A. (2011). Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population. Nature Nanotechnology, 7, 62–68.CrossRefGoogle Scholar
  53. 53.
    Hendry, S. L., et al. (2008). Multimodal evaluation of in vivo magnetic resonance imaging of myocardial restoration by mouse embryonic stem cells. The Journal of Thoracic and Cardiovascular Surgery, 136, 1028–1037.e1.CrossRefGoogle Scholar
  54. 54.
    Kim, P. J., et al. (2015). Direct evaluation of myocardial viability and stem cell engraftment demonstrates salvage of the injured myocardium. Circulation Research, 116, e40–e50.CrossRefGoogle Scholar
  55. 55.
    Blakemore, R. (1975). Magnetotactic bacteria. Science, 190, 377–379.CrossRefGoogle Scholar
  56. 56.
    Yan, L., et al. (2012). Magnetotactic bacteria, magnetosomes and their application. Microbiological Research, 167, 507–519.CrossRefGoogle Scholar
  57. 57.
    Schüler, D., & Frankel, R. B. (1999). Bacterial magnetosomes: Microbiology, biomineralization and biotechnological applications. Applied Microbiology and Biotechnology, 52, 464–473.CrossRefGoogle Scholar
  58. 58.
    Arakaki, A., Nakazawa, H., Nemoto, M., Mori, T., & Matsunaga, T. (2008). Formation of magnetite by bacteria and its application. Journal of the Royal Society, Interface, 5, 977–999.CrossRefGoogle Scholar
  59. 59.
    Araujo, A. C. V., Abreu, F., Silva, K. T., Bazylinski, D. A., & Lins, U. (2015). Magnetotactic bacteria as potential sources of bioproducts. Marine Drugs, 13, 389–430.CrossRefGoogle Scholar
  60. 60.
    Mahmoudi, M., et al. (2016). Novel MRI contrast agent from magnetotactic bacteria enables in vivo tracking of iPSC-derived cardiomyocytes. Scientific Reports, 6.Google Scholar
  61. 61.
    Komeili, A. (2012). Molecular mechanisms of compartmentalization and biomineralization in magnetotactic bacteria. FEMS Microbiology Reviews, 36, 232–255.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Stanford Cardiovascular InstituteStanfordUSA
  2. 2.Division of Cardiovascular MedicineCenter for Clinical Science Research (CCSR); 3115C, Stanford University School of MedicineStanfordUSA

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