Publikationsserver der Universitätsbibliothek Marburg

Titel:Untersuchungen zu SPIO-Partikeln: SPIO-Markierung in vitro, Differenzierungspotential humaner mesenchymaler Stammzellen und Relaxivitätsmessungen.
Autor:Barkova, Ekaterina
Weitere Beteiligte: Jansen, Andreas (Prof. Dr. ) ; Hundt, Walter (Prof. Dr.)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0344
URN: urn:nbn:de:hebis:04-z2017-03447
DOI: https://doi.org/10.17192/z2017.0344
DDC: Naturwissenschaften
Titel(trans.):Investigations of SPIO particles: SPIO labeling in vitro, differentiation potential of human mesenchymal stem cells and relaxivity measurements.
Publikationsdatum:2017-06-15
Lizenz:https://creativecommons.org/licenses/by-sa/4.0

Dokument

Schlagwörter:
Stammzelle, superparamagnetic iron oxide particles, 7 Tesla, Relaxivität, magnetic resonance imaging, contrast agents, Kontrastmittel, SPIO-Partikel, SPIO particles, Nanopartikel, Kernspintomografie, superparamagnetische Eisenoxidpartikel, nanoparticles, SPIO-Markierung

Zusammenfassung:
Magnetische Nanopartikel finden eine breite biomedizinische Anwendung als Biosensoren und als KM in der Bildgebung, ferner werden sie eingesetzt, wenn eine gezielte Wirkstoffabgabe erreicht werden soll. Außerdem spielt die molekulare MRT eine wichtige Rolle bei der Tumordiagnostik. Die schnelle Entwicklung der Nanotechnologie und die zunehmende Anzahl unterschiedlicher Nanomaterialien, die aufgrund ihrer besonderen physikalischen Eigenschaften und der guten Biokompatibilität metallischer und anorganischer Nanopartikel zum Einsatz kommen, führen dazu, dass immer mehr neue Nanostrukturen in Kontakt mit Mensch und Umwelt kommen. Eisenoxidbasierte MRT-Kontrastmittel umfassen SPIO-Partikel. Sie werden klinisch bei der Leberbildgebung eingesetzt und vom mononukleären Phagocytensystem aufgenommen. Außerdem können Zellen mit SPIO-Partikeln markiert und als In-vivo-Kontrastmarker für die MRT-Bildgebung verwendet werden. Bei der Zellmarkierungstechnik sollen unterschiedliche Parameter optimiert werden, z. B. Größe, Beschichtung und Dosis der Partikel sowie die Inkubationszeit. Derzeit liegt deshalb der Fokus vieler Studien auf modifizierten und unterschiedlich beschichteten SPIO-Partikeln. In der vorliegenden Arbeit wurden 2 verschiedene SPIO-Formulierungen getestet und es wurde die Aufnahme der SPIO-Partikel in unterschiedliche Zelltypen – murine Makrophagen, humane leukämische Monocyten sowie humane mesenchymale Stammzellen – untersucht. Viele Forscher versuchen eine spezifische Markierung durch modifizierte SPIO-Partikel zu erreichen. Hierbei gibt es allerdings starke Bedenken, was die Biosicherheit solcher Partikel angeht. In dieser Arbeit wurden SPIO-Formulierungen verwendet, die ohne Modifizierungen und bei einer relativ niedrigen Konzentration gute Ergebnisse erzielten. Phagocytierende Zellen wurden mit 2,79 µg Fe/ml und 27,92 µg Fe/ml inkubiert. Nach 12 h lag der Eisengehalt pro J774A.1-Zelle bei 13,77 ± 0,5 pg. Bei THP-1-Zellen konnte eine geringere Aufnahme beobachtet werden, das intrazelluläre Eisen betrug 24 h nach der Markierung 9,84 ± 1,6 pg Fe pro Zelle. Aufgrund ihrer hervorragenden Eigenschaften besitzen Stammzellen ein großes Potential in der regenerativen Medizin. Die Mechanismen, die der Transplantation von Stammzellen in ein Target-Organ zugrunde liegen, sind jedoch noch nicht verstanden. Nach einer Markierung der Zellen mit SPIO-Partikeln kann die Migration der Zellen nach der Transplantation mittels MRT beobachtet werden. In dieser Arbeit wurden humane mesenchymale Stammzellen mit SPIO, aber ohne die Hilfe eines Transfektionsagens markiert. Bei der Markierung der Stammzellen wurde mit einer höheren Konzentration von SPIO-Partikeln (25 µg Fe/ml) im Vergleich zur Markierung phagocytierender Zellen begonnen. Die Markierung von hMSC war effizient. Eine der wichtigsten Eigenschaften von Stammzellen ist ihre Differenzierungsfähigkeit, die in dieser Arbeit ebenfalls untersucht wurde. Die Markierung mit SPIO-Partikeln beeinflusste das Differenzierungspotential von hMSC zu Osteoblasten und Adipocyten nicht. Um herauszufinden, ob SPIO-Partikel einen T2-verstärkenden Effekt haben, wurden die T1- und T2-Werte unterschiedlicher KM-Lösungen bei 7 T gemessen und das r2/r1-Verhältnis berechnet. Sowohl 1/T1 als auch 1/T2 nahmen linear mit der SPIO-Konzentration zu. Für das untersuchte eisenoxidhaltige KM wurde ein r2-Wert von 178 mM-1s-1 in Wasser ermittelt. Das Verhältnis r2/r1 lag bei 66 (gemessen in Wasser). Mit Erhöhung der Viskosität nahm auch r2 zu, sodass in Mausplasma ein r2-Wert von 184,6 mM-1s-1 bestimmt wurde. Die getesteten SPIO-Partikel wiesen ein Verhältnis r2/r1 von 108,6 bei 7 T auf (in Mausplasma, gemessen bei RT). Die bei 7 T zu erwartenden höheren r2-Werte im Vergleich zu einem aus der Literatur bekannten Wert von Ferucarbotran (diente als Referenz-KM), gemessen bei 4,7 T, konnten nicht beobachtet werden, was an den unterschiedlichen Temperaturen und einer möglichen Feldinhomogenität bei den Messungen liegen könnte.

Summary:
Magnetic nanoparticles are widely used in biomedical sciences as biosensors and as contrast agents in imaging applications. They are also used if the targeted release of a drug is required. In addition, molecular MRI plays an important part in tumor diagnostics. Due to the rapid development of nanotechnology, the increasing number of different nanomaterials which are used because of their special physical properties, and the good biocompatibility of metal and anorganic nanoparticles, a growing number of new nanostructures come into contact with man and environment. Iron oxide based MRI contrast agents include SPIO particles. They are used clinically in liver imaging and absorbed by the mononuclear phagocyte system. Moreover, cells can be labeled with SPIO particles and used as in vivo contrast markers for MR-Imaging. The cell labeling technique should optimize various parameters, such as size, coating and particle dose as well as incubation time. For this reason, the current focus of many studies is on modified and differently coated SPIO particles. For the present thesis, two different SPIO formulations were tested and the uptake of SPIO particles into various cell types – murine macrophages, human leucaemic monocytes and human mesenchymal stem cells – has been studied. Many researchers try to achieve a specific labeling by modified SPIO particles. In this respect, however, there are strong doubts concerning the biosafety of these particles. In this thesis, SPIO formulations that achieved good results without modifications and at a relatively low concentration were used. Phagocytic cells were incubated with 2.79 µg Fe/ml and 27.92 µg Fe/ml. After 12 h, the iron concentration per J774A.1 cell was 13.77 ± 0.5 pg. With THP-1 cells, a lower uptake could be observed; the intracellular iron was 9.84 ± 1.6 pg Fe per cell 24 h after labeling. Due to their outstanding properties, stem cells have great potential in regenerative medicine. Nevertheless, the mechanisms on which the transplantation of stem cells into a target organ is based are not yet understood. After labeling the cells with SPIO particles, cell migration can be observed by means of MRI after transplantation. For this study, human mesenchymal stem cells were labeled with SPIO, but without the aid of a transfection agent. Labeling the stem cells was started with a higher concentration of SPIO particles (25 µg Fe/ml) compared to the labeling of phagocytic cells. Labeling of hMSC was efficient. One of the most important properties of stem cells is their ability to differentiate, which was investigated in this thesis as well. The labeling with SPIO particles did not affect the differentiation potential of hMSC to osteoblasts and adipocytes. To determine if SPIO particles have a T2-intensifying effect, the T1 and T2 values of various contrast agent solution at 7 T were measured and the r2/r1 ratio calculated. Both 1/T1 and 1/T2 increased linearly with the SPIO concentration. For the iron oxide containing contrast agent under analysis, an r2 value of 178 mM-1s-1 in water was determined. The r2/r1 ratio was 66 (measured in water). With an increase of the viscosity, r2 also increased so that an r2 value of 184.6 mM-1s-1 in mouse plasma was determined. The tested SPIO particles showed an r2/r1 ratio of 108.6 at 7 T (in mouse plasma, measured at RT). The higher r2 values expected at 7 T, compared to published reference contrast agent Ferucarbotran values when measure at 4.7 T, were not observed. This may have been due to the different temperatures and a possible field inhomogeneity during the measurements.

Bibliographie / References

  1. 159. Pooley, R. A. AAPM/RSNA physics tutorial for residents: fundamental physics of MR imaging, Radoographics 25, 1087-1099 (2005).
  2. 113. Kohro, T. et al. A Comparison of Differences in the Gene Expression Profiles of Phorbol 12-Myristate 13-Acetate Differentiated THP-1 Cells and Human MonocyteDerived Macrophage, Journal of Atherosclerosis and Thrombosis, 11, 88-97 (2004).
  3. 173. Salasznyk, R. M. Williams, W. A. Boskey, A. Batorsky, A. & Plopper, G. E. Adhesion to Vitronectin and Collagen I Promotes Osteogenic Differentiation of Human Mesenchymal Stem Cells, J. Biomed. Biotechnol. 2004, 24-34 (2004).
  4. 208. Tögel, F. Hu, Z. Weiss, K. Isaac, J. Lange, C. & Westenfelder, C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms, Am. J. Physiol. Renal Physiol. 289, F31-42 (2005).
  5. 49. Chang, Y.-K. Liu, Y.-P. Ho, J. H. Hsu, S.-C. & Lee, O. K. Amine-surface-modified superparamagnetic iron oxide nanoparticles interfere with differentiation of human mesenchymal stem cells, J. Orthop. Res. 30, 1499-1506 (2012).
  6. 93. Ito, A. et al. A new methodology of mesenchymal stem cell expansion using magnetic nanoparticles, Biochemical Engineering Journal 20, 119-125 (2004).
  7. 82. Ho, C. & Hitchens, T. K. A non-invasive approach to detecting organ rejection by MRI: monitoring the accumulation of immune cells at the transplanted organ, Curr. Pharm. Biotechnol. 5, 551-566 (2004).
  8. 59. Crichton, R. R. & Ward, R. J. An overview of iron metabolism: molecular and cellular criteria for the selection of iron chelators, Curr. Med. Chem. 10, 997-1004 (2003).
  9. 72. Guo, J. Lin, G. S. Bao, C. Y. Hu, Z. M. & Hu, M. Y. Anti-inflammation role for mesenchymal stem cells transplantation in myocardial infarction, Inflammation 30, 97-104 (2007).
  10. 230. Weissleder, R. Lee, A. S. Khaw, B. A. Shen, T. & Brady, T. J. Antimyosin-labeled monocrystalline iron oxide allows detection of myocardial infarct: MR antibody imaging, Radiology 182, 381-385 (1992).
  11. 84. Hori, J. Deie, M. Kobayashi, T. Yasunaga, Y. Kawamata, S. & Ochi, M. Articular cartilage repair using an intra-articular magnet and synovium-derived cells, J. Orthop. Res. 29, 531-538 (2011).
  12. 194. Sun, J.-H. et al. Assessment of biological characteristics of mesenchymal stem cells labeled with superparamagnetic iron oxide particles in vitro, Mol. Med. Rep. 5, 317- 320 (2012).
  13. 100. Janssens, S. et al. Autologous bone marrow-derived stem-cell transfer in patients with ST-segment elevation myocardial infarction: double-blind, randomised controlled trial, Lancet 367, 113-121 (2006).
  14. 193. Stamm, C. et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration, Lancet 361, 45-46 (2003).
  15. 153. Oshima, Y. Watanabe, N. Matsuda, K. Takai, S. Kawata, M. & Kubo, T. Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation, J. Histochem. Cytochem. 53, 207-216 (2005).
  16. 131. Lu, C.-W. et al. Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling, Nano Lett. 7, 149-154 (2007).
  17. 58. Cova, L. et al. Biocompatible fluorescent nanoparticles for in vivo stem cell tracking, Nanotechnology 24, 245603 (2013).
  18. 94. Ito, T. Suzuki, A. Imai, E. Okabe, M. & Hori, M. Bone marrow is a reservoir of repopulating mesangial cells during glomerular remodeling, J. Am. Soc. Nephrol. 12, 2625- 2635 (2001).
  19. 126. Li, X. et al. Bone marrow mesenchymal stem cells differentiate into functional cardiac phenotypes by cardiac microenvironment, J. Mol. Cell. Cardiol. 42, 295-303 (2007).
  20. 116. Krampera, M. et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide, Blood 101, 3722- 3729 (2003).
  21. 137. Metz, S. Bonaterra, G. Rudelius, M. Settles, M. Rummeny, E. J. & Daldrup-Link, H. E. Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro, Eur. Radiol. 14, 1851-1858 (2004).
  22. 133. Mailänder, V. et al. Carboxylated superparamagnetic iron oxide particles label cells intracellularly without transfection agents, Mol. Imaging Biol. 10, 138-146 (2008).
  23. 144. Nabi, I. R. & Le, P. U. Caveolae/raft-dependent endocytosis, The Journal of Cell Biology 161, 673-677 (2003).
  24. 130. Liu, G. et al. Cell labeling efficiency of layer-by-layer self-assembly modified silica nanoparticles, J. Mater. Res. 24, 1317-1321 (2009).
  25. 117. Kumari, A. & Yadav, S. K. Cellular interactions of therapeutically delivered nanoparticles, Expert Opin. Drug Deliv. 8, 141-151 (2011).
  26. 181. Schulze, E. Ferucci J. T. Poss, K. Lapointe, L. Bogdanova, A. & Weissleder, R. Cellular uptake and trafficking of a prototypical magnetic iron oxide label in vitro, Invest Radiol 30, 604-610 (1995).
  27. 40. Bulte, J. W. Kraitchman, D. L. Mackay, A. M. & Pittenger, M. F. Chondrogenic differentiation of mesenchymal stem cells is inhibited after magnetic labeling with ferumoxides, Blood 104, 3410-2; author reply 3412-3 (2004).
  28. 152. Ortega-Vinuesa, J. L. Martin-Rodriguez, A. & Hidalgo-Alvarez, R. Colloidal Stability of Polymer Colloids with Different Interfacial Properties: Mechanisms, Journal of colloid and interface science 184, 259-267 (1996).
  29. 170. Riemer, J. Hoepken, H. H. Czerwinska, H. Robinson, S. R. & Dringen, R. Colorimetric ferrozine-based assay for the quantitation of iron in cultured cells, Anal. Biochem. 331, 370-375 (2004).
  30. 106. Kalish, H. et al. Combination of transfection and magnetic resonance contrast agents for cellular imaging: Relationship between relaxivities, electrostatic forces, and chemical composition, Magnetic Resonance In Medicine: Official Journal Of The Society Of Magnetic Resonance In Medicine / Society Of Magnetic Resonance In Medicine 50 (2003 Aug).
  31. 171. Rohrer, M. Bauer, H. Mintorovitch, J. Requardt, M. & Weinmann, H.-J. Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths, Invest. Radiol. 40, 715-724 (2005).
  32. 54. Chen, I. Y. et al. Comparison of optical bioluminescence reporter gene and superparamagnetic iron oxide MR contrast agent as cell markers for noninvasive imaging of cardiac cell transplantation, Mol. Imaging Biol. 11, 178-187 (2009).
  33. 127. Li, Z. et al. 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 26, 864-873 (2008).
  34. 122. Lee, J. W. Fang, X. Krasnodembskaya, A. Howard, J. P. & Matthay, M. A. Concise Review: Mesenchymal Stem Cells for Acute Lung Injury: Role of Paracrine Soluble Factors, Stem Cells 29, 913-919 (2011).
  35. 74. Hamm, B. et al. Contrast-enhanced MR imaging of liver and spleen: first experience in humans with a new superparamagnetic iron oxide, J. Magn. Reson. Imaging 4, 659-668 (1994).
  36. 41. Bussolati, B. Tetta, C. & Camussi, G. Contribution of stem cells to kidney repair, Am J Nephrol. 28, 813-822 (2008).
  37. 97. Jackson, S. A. & Thomas, R. M. CT, MRT, Ultraschall auf einen Blick. 1 Aufl., Elsevier, München (2009).
  38. 107. Kaminski, A. & Steinhoff, G. Current status of intramyocardial bone marrow stem cell transplantation, Semin. Thorac. Cardiovasc. Surg. 20, 119-125 (2008).
  39. 125. Lewinski, N. Colvin, V. & Drezek, R. Cytotoxicity of nanoparticles, Small 4, 26-49 (2008).
  40. 56. Chithrani, B. D. Ghazani, A. A. & Chan, W. C. W. Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells, Nano Lett. 6, 662- 668 (2006).
  41. 195. Suzuki, M. Honda, H. Kobayashi, T. Wakabayashi, T. Yoshida, J. & Takahashi, M. Development of a target-directed magnetic resonance contrast agent using monoclonal antibody-conjugated magnetic particles, Noshuyo Byori 13, 127-132 (1996).
  42. 197. Tassa, C. Shaw, S. Y. & Weissleder, R. Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy, Acc. Chem. Res. 44, 842-852 (2011).
  43. 182. Schwende, H. Fitzke, E. Ambs, P. and Dieter, P. Differences in the State of Differentiation of THP-1 Cells Induced by Phorbol Ester and 1,25-Dihydroxyvitamin D3, Journal of Leukocyte Biollogy 59, 555-561 (1996).
  44. 132. Lunov, O. et al. Differential uptake of functionalized polystyrene nanoparticles by human macrophages and a monocytic cell line, ACS Nano 5, 1657-1669 (2011).
  45. 77. Heino, T. J. & Hentunen, T. A. Differentiation of osteoblasts and osteocytes from mesenchymal stem cells, Curr. Stem Cell Res. Ther. 3, 131-145 (2008).
  46. 237. Yang, C.-Y. et al. Direct labeling of hMSC with SPIO: the long-term influence on toxicity, chondrogenic differentiation capacity, and intracellular distribution, Mol. Imaging. Biol. 13, 443-451 (2011a).
  47. 50. Chao, Y. et al. Direct recognition of superparamagnetic nanocrystals by macrophage scavenger receptor SR-AI, ACS Nano 7, 4289-4298 (2013).
  48. 118. Lagaly, G. Schulz, O. & Zimehl, R. Dispersionen und Emulsionen. Eine Einführung in die Kolloidik feinverteilter Stoffe einschließlich der Tonminerale (Steinkopff, Darmstadt, 1997).
  49. 115. Kraitchman, D. L. et al. Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction, Circulation 112, 1451-1461 (2005).
  50. 156. Peng, C. et al. Effect of transplantation with autologous bone marrow stem cells on acute myocardial infarction, Int. J. Cardiol. 162, 158-165 (2013).
  51. 67. Farrell, E. et al. Effects of iron oxide incorporation for long term cell tracking on MSC differentiation in vitro and in vivo, Biochem. Biophys. Res. Commun. 369, 1076-1081 (2008).
  52. 189. So, P.-W. et al. Efficient and rapid labeling of transplanted cell populations with superparamagnetic iron oxide nanoparticles using cell surface chemical biotinylation for in vivo monitoring by MRI, Cell Transplant. 19, 419-429 (2010).
  53. 146. Neri, M. et al. Efficient in vitro labeling of human neural precursor cells with superparamagnetic iron oxide particles: relevance for in vivo cell tracking, Stem Cells 26, 505-516 (2008).
  54. 111. Kittel, C., Einführung in die Festkörperphysik, R. Oldenbourg Verlag, München, 12 Aufl. (1999)
  55. 65. Ehrlich, M. et al. Endocytosis by random initiation and stabilization of clathrin-coated pits, Cell 118, 591-605 (2004).
  56. 210. Tsuchiya, S. Yamabe, M. Yamaguchi, Y. Kobayashi, Y. Konno, T. & Tada, K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1), Int. J. Cancer 26, 171-176 (1980).
  57. 154. Pawelczyk, E. Arbab, A. S. Pandit, S. Hu, E. & Frank, J. A. Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging, NMR Biomed. 19, 581-592 (2006).
  58. 114. Kostura, L. Kraitchman, D. L. Mackay, A. M. Pittenger, M. F. & Bulte, J. W. Feridex labeling of mesenchymal stem cells inhibits chondrogenesis but not adipogenesis or osteogenesis, NMR Biomed. 17, 513-517 (2004).
  59. 213. van Buul, G. M. et al. Ferumoxides-protamine sulfate is more effective than ferucarbotran for cell labeling: implications for clinically applicable cell tracking using MRI, Contrast Media Mol. Imaging 4, 230-236 (2009).
  60. 161. Quintavalla, J. et al. Fluorescently labeled mesenchymal stem cells (MSCs) maintain multilineage potential and can be detected following implantation into articular cartilage defects, Biomaterials 23, 109-119 (2002).
  61. 90. Hunter, R. J. Foundations of colloid science (Clarendon Press, 2nd ed. Oxford, 2001).
  62. 164. Reddy, A. M. et al. Functional characterization of mesenchymal stem cells labeled with a novel PVP-coated superparamagnetic iron oxide, Contrast Media Mol. Imaging 4, 118-126 (2009).
  63. 178. Schäfer, R. et al. Functional investigations on human mesenchymal stem cells exposed to magnetic fields and labeled with clinically approved iron nanoparticles, BMC Cell Biol. 11, 22 (2010).
  64. 221. Vuu, K. et al. Gadolinium-rhodamine nanoparticles for cell labeling and tracking via magnetic resonance and optical imaging, Bioconjug. Chem. 16, 995-999 (2005).
  65. 123. Lee, J.-h. et al. Heparin-coated superparamagnetic iron oxide for in vivo MR imaging of human MSCs, Biomaterials 33, 4861-4871 (2012).
  66. 165. Reimer, P. & Tombach, B. Hepatic MRI with SPIO: detection and characterization of focal liver lesions, Eur. Radiol. 8, 1198-1204 (1998).
  67. 184. Sgodda, M. et al. Hepatocyte differentiation of mesenchymal stem cells from rat peritoneal adipose tissue in vitro and in vivo, Experimental Cell Research 313, 2875- 2886 (2007).
  68. 105. Josephson, L. Tung, C. H. Moore, A. & Weissleder, R. High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates, Bioconjug. Chem. 10, 186-191 (1999).
  69. 211. Unger, E. C. How can superparamagnetic iron oxides be used to monitor disease and treatment?, Radiology 229, 615-616 (2003).
  70. 136. Meisel, R. Zibert, A. Laryea, M. Göbel, U. Däubener, W. & Diloo, D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation, Blood 103, 4619-4621 (2004).
  71. 62. Di Nicola, M. et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli, Blood 99, 3838-3843 (2002).
  72. 209. Toma, C. Human Mesenchymal Stem Cells Differentiate to a Cardiomyocyte Phenotype in the Adult Murine Heart, Circulation 105, 93-98 (2002).
  73. 42. Canzi, L. et al. Human skeletal muscle stem cell antiinflammatory activity ameliorates clinical outcome in amyotrophic lateral sclerosis models, Mol. Med. 18, 401-411 (2012).
  74. 142. Moore, A. Josephson, L. Bhorade, R. M. Basilion, J. P. & Weissleder, R. Human transferrin receptor gene as a marker gene for MR imaging, Radiology 221, 244-250 (2001).
  75. 187. Sigmund, W., Pyrgiotakis, G. & Daga, A. “II Powder Processing at the Nanoscale „Theory and Application of colloidal Processing“, ” in Chemical Processing of Ceramics, Lee B. I. and Komarneni, S. Eds., ed: CRC Press (2005)
  76. 45. Centeno, C. J. Busse, D. Kisiday, J. Keohan, C. Freeman, M. & Karli, D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells, Pain Physician 11, 343-353 (2008).
  77. 240. Yokoyama, M. Miwa, H. Maeda, S. Wakitani, S. & Takagi, M. Influence of fetal calf serum on differentiation of mesenchymal stem cells to chondrocytes during expansion, J. Biosci. Bioeng. 106, 46-50 (2008).
  78. 176. Scavo, L. M. Karas, M. Murray, M. & Leroith, D. Insulin-like growth factor-I stimulates both cell growth and lipogenesis during differentiation of human mesenchymal stem cells into adipocytes, J. Clin. Endocrinol. Metab. 89, 3543-3553 (2004).
  79. 192. Soria, B. Roche, E. Berna, G. Leon-Quinto, T. Reig, J. A. & Martin, F. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocininduced diabetic mice, Diabetes 49, 157-162 (2000).
  80. 143. Mosqueira, V. C. Legrand, P. Gref, R. Heurtault, B. Appel, M. & Barratt, G. Interactions between a macrophage cell line (J774A1) and surface-modified poly (D,L-lactide) nanocapsules bearing poly(ethylene glycol), J. Drug Target. 7, 65-78 (1999).
  81. 48. Chang, J.-S. Chang, K. L., Hwang, D.-F. & Kong, Z.-L. In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line, Environ. Sci. Technol. 41, 2064-2068 (2007).
  82. 88. Hu, S.-L. et al. In vitro labeling of human umbilical cord mesenchymal stem cells with superparamagnetic iron oxide nanoparticles, J. Cell. Biochem. 108, 529-535 (2009).
  83. 110. Kircher, M. F. et al. In vivo high resolution three-dimensional imaging of antigenspecific cytotoxic T-lymphocyte trafficking to tumors, Cancer Res. 63, 6838-6846 (2003).
  84. 75. He, G. et al. In vivo imaging of bone marrow mesenchymal stem cells transplanted into myocardium using magnetic resonance imaging: a novel method to trace the transplanted cells, International Journal of Cardiology 114, 4-10 (2007 Jan 2).
  85. 96. Ittrich, H. et al. In vivo magnetic resonance imaging of iron oxide-labeled, arteriallyinjected mesenchymal stem cells in kidneys of rats with acute ischemic kidney injury: detection and monitoring at 3T, J. Magn. Reson. Imaging 25, 1179-1191 (2007).
  86. 87. Hu, S.-L. et al. In vivo magnetic resonance imaging tracking of SPIO-labeled human umbilical cord mesenchymal stem cells, J. Cell. Biochem. 113, 1005-1012 (2012).
  87. 37. Bulte, J. W. Duncan, I. D. & Frank, J. A. In vivo magnetic resonance tracking of magnetically labeled cells after transplantation, J. Cereb. Blood Flow Metab. 22, 899- 907 (2002b).
  88. 112. Ko, I. K. Song, H. T. Cho, E. J. Lee, E. S. Huh, Y. M. & Suh, J. S. In vivo MR Imaging of Tissue-engineered Human Mesenchymal Stem Cells Transplanted to Mouse: a Preliminary Study, Ann. Biomed. Eng. 35, 101-108 (2007).
  89. 103. Jing, X. H. et al. In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection. Joint Bone Spine: Revue Du Rhumatisme 75, 432-438 (2008 Jul).
  90. 43. Cao, A. H. Shi, H. J. Zhang, Y. & Teng, G. J. In vivo tracking of dual-labeled mesenchymal stem cells homing into the injured common carotid artery, Anat. Rec. (Hoboken) 292, 1677-1683 (2009).
  91. 196. Sykova, E. & Jendelova, P. In vivo tracking of stem cells in brain and spinal cord injury, Prog. Brain Res. 161, 367-383 (2007).
  92. 128. Link, G. Pinson, A. & Hershko, C. Iron loading of cultured cardiac myocytes modifies sarcolemmal structure and increases lysosomal fragility, J. Lab. Clin. Med. 121, 127- 134 (1993).
  93. 66. Emerit, J. Beaumont, C. & Trivin, F. Iron metabolism, free radicals, and oxidative injury, Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie (2001 Jul).
  94. 80. Heymer, A. et al. Iron oxide labelling of human mesenchymal stem cells in collagen hydrogels for articular cartilage repair, Biomaterials 29, 1473-1483 (2008).
  95. 38. Bulte, J. W. & Kraitchman, D. L. Iron oxide MR contrast agents for molecular and cellular imaging, NMR Biomed. 17, 484-499 (2004a).
  96. 134. Malhi, H. Irani, A. N. Gagandeep, S. & Gupta, S. Isolation of human progenitor liver epithelial cells with extensive replication capacity and differentiation into mature hepatocytes, J. Cell. Sci. 115, 2679-2688 (2002).
  97. 99. Janssen, J. J. M. Baltussen, J. J. M. van Gelder, A. P. & Perenboom, J. A. A. J. Kinetics of magnetic flocculation. II. Flocculation of coarse particles, J. Phys. D: Appl. Phys. 23, 1455-1460 (1990).
  98. 129. Lissner, J. & Baierl, P. (Hrsg.) (1990): Klinische Kernspintomographie. 2. Aufl. Enke, Stuttgart.
  99. 191. Song, M. Moon, W. K. Kim, Y. Lim, D. Song, I.-C. & Yoon, B.-W. Labeling efficacy of superparamagnetic iron oxide nanoparticles to human neural stem cells: comparison of ferumoxides, monocrystalline iron oxide, cross-linked iron oxide (CLIO)-NH2 and tatCLIO, Korean J. Radiol. 8, 365-371 (2007).
  100. 179. Schäfer, R. et al. Labeling of human mesenchymal stromal cells with superparamagnetic iron oxide leads to a decrease in migration capacity and colony formation ability, Cytotherapy 11, 68-78 (2009).
  101. 190. Soenen, S. J. De Smedt, S. C. & Braeckmans, K. Limitations and caveats of magnetic cell labeling using transfection agent complexed iron oxide nanoparticles, Contrast Media Mol. Imaging 7 (2), 140-52 (2012)
  102. 183. Serda, R. E. et al. Logic-embedded vectors for intracellular partitioning, endosomal escape, and exocytosis of nanoparticles, Small 6, 2691-2700 (2010).
  103. 231. Weissleder, R. Bogdanov, A. Neuwelt, E. A. & Papisov, M. Long-circulating iron oxides for MR imaging, Advanced Drug Delivery Reviews 16, 321-334 (1995).
  104. 163. Raynal, I. Prigent, P. Peyramaure, S. Najid, A. Rebuzzi, C. & Corot, C. Macrophage endocytosis of superparamagnetic iron oxide nanoparticles: mechanisms and comparison of ferumoxides and ferumoxtran-10, Invest. Radiol. 39, 56-63 (2004).
  105. 202. Taylor, P. R. Martinez-Pomarez, L. Stacey, M. Lin, H. H. Brown, G. D. & Gordon, S. Macrophage receptors and immune recognition, Annu. Rev. Immunol. 23, 901- 944 (2005).
  106. 185. Shi, X.-L. Gu, J. Y. Han, B. Xu, H. Y. Fang, L. & Ding, Y. T. Magnetically labeled mesenchymal stem cells after autologous transplantation into acutely injured liver, World J. Gastroenterol. 16, 3674-3679 (2010).
  107. 121. Lawaczeck, R. et al. Magnetic iron oxide particles coated with carboxydextran for parenteral administration and liver contrasting. Pre-clinical profile of SH U555A, Acta Radiol. 38, 584-597 (1997).
  108. 85. Hsiao, J.-K. et al. Magnetic nanoparticle labeling of mesenchymal stem cells without transfection agent: cellular behavior and capability of detection with clinical 1.5 T magnetic resonance at the single cell level, Magn. Reson. Med. 58, 717-724 (2007).
  109. 239. Yang, K. et al. Magnetic resonance evaluation of transplanted mesenchymal stem cells after myocardial infarction in swine, Can. J. Cardiol. 27, 818-825 (2011).
  110. 203. Terrovitis, J. V. et al. Magnetic resonance imaging of ferumoxide-labeled mesenchymal stem cells seeded on collagen scaffolds-relevance to tissue engineering, Tissue Eng. 12, 2765-2775 (2006).
  111. 108. Kang, H. W. Josephson, L. Petrovsky, A. Weissleder, R. & Bogdanov, A. Magnetic resonance imaging of inducible E-selectin expression in human endothelial cell culture, Bioconjug. Chem. 13, 122-127 (2002).
  112. 119. Lalande, C. et al. Magnetic resonance imaging tracking of human adipose derived stromal cells within three-dimensional scaffolds for bone tissue engineering, Eur. Cell Mater. 21, 341-354 (2011).
  113. 148. Nishida, K. et al. Magnetic targeting of bone marrow stromal cells into spinal cord: through cerebrospinal fluid, Neuroreport 17, 1269-1272 (2006).
  114. 238. Yang, C.-Y. et al. Mechanism of cellular uptake and impact of ferucarbotran on macrophage physiology, PLoS ONE 6, e25524 (2011b).
  115. 64. Doherty, G. J. & McMahon, H. T. Mechanisms of endocytosis, Annu. Rev. Biochem. 78, 857-902 (2009).
  116. 175. Satija, N. K. et al. Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine, Journal of Cellular and Molecular Medicine 13, 4385-4402 (2009).
  117. 86. Hsiao, J.-K. et al. Mesoporous silica nanoparticles as a delivery system of gadolinium for effective human stem cell tracking, Small 4, 1445-1452 (2008).
  118. 174. Saldanha, K. J. Doan, R. P. Ainslie, K. M. Desai, T. A. & Majumdar, S. Micrometersized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering, Magn. Reson. Imaging 29, 40-49 (2011).
  119. 70. Genre, D. et al. Modulations of dose intensity of doxorubicin and cyclophosphamide in association with G-CSF and peripheral blood stem cells in adjuvant chemotherapy for breast cancer: comparative evaluation of completion and safety of three intensive regimens, Bone Marrow Transplant. 29, 881-886 (2002).
  120. 60. Crichton, R. R. Wilmet, S. Legssyer, R. & Ward, R. J. Molecular and celluar mechanisms of iron homeostasis and toxicity in mammalian cells, Journal Of Inorganic Biochemistry (2002 Jul 25).
  121. 39. Bulte, J. W. & Kraitchman, D. L. Monitoring cell therapy using iron oxide MR contrast agents, Curr. Pharm. Biotechnol. 5, 567-584 (2004b).
  122. 83. Hoehn, M. et al. Monitoring of implanted stem cell migration in vivo: a highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat, Proc. Natl. Acad. Sci. U.S.A. 99, 16267-16272 (2002).
  123. 36. Bulte, J. W. et al. Monitoring stem cell therapy in vivo using magnetodendrimers as a new class of cellular MR contrast agents, Acad. Radiol. 9 Suppl 2, S332-5 (2002a).
  124. 207. To, S. Y. Castro, D. J. Lufkin, R. B. Soudant, J. & Saxton, R. E. Monoclonal antibody-coated magnetite particles as contrast agents for MR imaging and laser therapy of human tumors, J. Clin. Laser Med. Surg. 10, 159-169 (1992).
  125. 47. Cerdan, S. Lötscher, H. R. Künnecke, B. & Seelig, J. Monoclonal antibody-coated magnetite particles as contrast agents in magnetic resonance imaging of tumors, Magn. Reson. Med. 12, 151-163 (1989).
  126. 53. Chen, H.-Z. et al. [MR imaging of polyethylenimine-superparamagnetic iron oxide nanoparticle labeled bone marrow mesenchymal stem cells in vitro], Sichuan Da Xue Xue Bao Yi Xue Ban 43, 578-583 (2012).
  127. 52. Chen, G. et al. MRI-visible polymeric vector bearing CD3 single chain antibody for gene delivery to T cells for immunosuppression, Biomaterials 30, 1962-1970 (2009).
  128. 167. Remsen, L. G. et al. MR of carcinoma-specific monoclonal antibody conjugated to monocrystalline iron oxide nanoparticles: the potential for noninvasive diagnosis, AJNR Am. J. Neuroradiol. 17, 411-418 (1996).
  129. 158. Pittenger, M. F. Multilineage Potential of Adult Human Mesenchymal Stem Cells, Science 284, 143-147 (1999).
  130. 226. Wegner, K., Pratsinis, S. E. & Köhler, M (2003): Nanomaterialien und Nanotechnologie, S. 821-905, in Winnacker/Küchler: Chemische Technik: Prozesse und Produkte, Band 2. Neue Technologien, Wiley-VCH Verlag.
  131. 34. Bulte, J. W. et al. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination, Proc. Natl. Acad. Sci. U.S.A. 96, 15256-15261 (1999).
  132. 199. Taupitz, M. et al. New generation of monomer-stabilized very small superparamagnetic iron oxide particles (VSOP) as contrast medium for MR angiography: preclinical results in rats and rabbits, J. Magn. Reson. Imaging 12, 905-911 (2000).
  133. 147. Niemeyer, M. et al. Non-invasive tracking of human haemopoietic CD34+ stem cells in vivo in immunodeficient mice by using magnetic resonance imaging, Eur. Radiol. 20, 2184-2193 (2010).
  134. 98. Janic, B. et al. Optimization and validation of FePro cell labeling method, PLoS ONE 4, e5873 (2009).
  135. 186. Shi, X.-L. et al. Optimization of an effective directed differentiation medium for differentiating mouse bone marrow mesenchymal stem cells into hepatocytes in vitro, Cell Biology International. 32, 959-965 (2008).
  136. 101. Jasmin et al. Optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging, J. Nanobiotechnology 9, 4 (2011).
  137. 91. Hyink, D. P. & Abrahamson, D. R. Origin of the glomerular vasculature in the developing kidney, Semin. Nephrol. 15, 300-314 (1995).
  138. 120. Lauffer, R. B. Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design, Chem. Rev. 87, 901-927 (1987).
  139. 232. Weissleder, R. & Papisov, M. (1992): Pharmaceutical iron oxides for MR Imaging.
  140. 135. McLachlan, S. J. et al. Phase I clinical evaluation of a new iron oxide MR contrast agent, J. Magn. Reson. Imaging 4, 301-307 (1994).
  141. 200. Taupitz, M. et al. Phase I clinical evaluation of citrate-coated monocrystalline very small superparamagnetic iron oxide particles as a new contrast medium for magnetic resonance imaging, Invest. Radiol. 39, 394-405 (2004).
  142. 229. Weissleder, R. et al. Polyclonal human immunoglobulin G labeled with polymeric iron oxide: antibody MR imaging, Radiology 181, 245-249 (1991).
  143. 35. Bulte, J. W. Arbab, A. S. Douglas, T. & Frank, J. A. Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging, Meth. Enzymol. 386, 275-299 (2004).
  144. 150. Oberdörster, G. et al. Principles for characterizing the potential human health effects from exposure to nanomaterials: elements of a screening strategy, Part. Fibre Toxicol. 2, 8 (2005).
  145. 63. Digirolamo, C. M. Stokes, D. Colter, D. Phinney, D. G. Class, R. Prockop, D. J. Propagation and senescence of human marrow stromal cells in culture: a simple colonyforming assay identifies samples with the greatest potential to propagate and differentiate, British journal of haematology 107, 275-281 (1999).
  146. 102. Jing, Y. et al. Quantitative intracellular magnetic nanoparticle uptake measured by live cell magnetophoresis, FASEB J. 22, 4239-4247 (2008).
  147. 57. Corot, C. Robert, P. Idée, J.-M. & Port, M. Recent advances in iron oxide nanocrystal technology for medical imaging, Adv. Drug Deliv. Rev. 58, 1471-1504 (2006).
  148. 51. Chao, Y. et al. Recognition of dextran-superparamagnetic iron oxide nanoparticle conjugates (feridex) via macrophage scavenger receptor charged domains, Bioconjugate Chem. 23, 1003-1009.
  149. 79. Henning, T. D. et al. Relaxation effects of ferucarbotran-labeled mesenchymal stem cells at 1.5T and 3T: Discrimination of viable from lysed cells, Magn. Reson. Med. 62, 325-332 (2009b).
  150. 157. Pintaske, J. et al. Relaxivity of Gadopentetate Dimeglumine (Magnevist), Gadobutrol (Gadovist), and Gadobenate Dimeglumine (MultiHance) in human blood plasma at 0.2, 1.5, and 3 Tesla, Invest. Radiol. 41, 213-221 (2006).
  151. 222. Wakitani, S. Nawata, M. Tensho, K. Okabe, T. Machida, H. & Ohgushi, H. Repair of articular cartilage defects in the patello-femoral joint with autologous bone marrow mesenchymal cell transplantation: three case reports involving nine defects in five knees, J. Tissue Eng. Regen. Med. 1, 74-79 (2007).
  152. 162. Ralph, P. Prichard, J. & Cohn, M. Reticulum cell sarcoma: an effector cell in antibody-dependent cell-mediated immunity, J. Immunol. 114, 898-905 (1975).
  153. Rev. Magn. Reson. Med. 4: 1-20
  154. 109. Kim, J. A. Åberg, C. Salvati, A. & Dawson, K. A. Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population, Nat. Nanotechnol. 7, 62-68 (2012).
  155. 92. Imasawa, T. Roles of bone marrow cells in glomerular diseases, Clin. Exp. Nephrol. 7, 179-185 (2003).
  156. 46. Centeno, C. J. Schultz, J. R. Cheever, M. Robinson, B. Freeman, M & Marasco, W. Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique, Curr. Stem Cell Res. Ther. 5, 81-93 (2010).
  157. 201. Taylor, A. M. et al. Safety and preliminary findings with the intravascular contrast agent NC100150 injection for MR coronary angiography, J. Magn. Reson. Imaging 9, 220-227 (1999).
  158. 224. Wang, Z. et al. Self-assembly of magnetite nanocrystals with amphiphilic polyethylenimine: structures and applications in magnetic resonance imaging, J. Nanosci. Nanotechnol. 9, 378-385 (2009).
  159. 81. Hill, J. M. et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells, Circulation 108, 1009-1014 (2003).
  160. 205. Thorek DL & Tsourkas A. Size, charge and concentration dependent uptake of iron oxide particles by non-phagocytic cells, Biomaterials 29, 3583-3590 (2008 Sep).
  161. 145. Nejadnik, H. et al. Somatic differentiation and MR imaging of magnetically labeled human embryonic stem cells, Cell Transplant. 21, 2555-2567 (2012).
  162. 149. Novelline, R. A. Squire's Radiologie: Grundlagen der klinischen Diagnostik für Studium und Praxis. Dt. Bearb. 2. Auflage, Schattauer Stuttgart (2001).
  163. 44. Caravan, P. Strategies for increasing the sensitivity of gadolinium based MRI contrast agents, Chem. Soc. Rev. 35, 512-523 (2006).
  164. 225. Watson, D. J. Walton R. M. Magnitsky, S. G. Bulte, J. W. Poptani, H. & Wolfe, J. H. Structure-specific patterns of neural stem cell engraftment after transplantation in the adult mouse brain, Hum. Gene Ther. 17, 693-704 (2006).
  165. 172. Roohi, F. Lohrke, J. Ide, A. Schütz, G. & Dassler, K. Studying the effect of particle size and coating type on the blood kinetics of superparamagnetic iron oxide nanoparticles, Int. J. Nanomedicine 7, 4447-4458 (2012).
  166. 212. Valle-Delgado, J. J. Molina-Bolivar, J. A. Galisteo-Gonzalez, F. & Galvez-Ruiz, M. J. Study of the colloidal stability of an amphoteric latex, Colloid & Polymer Science 281, 708-715 (2003).
  167. 73. Gutteridge, J. M. Rowley D. A. & Halliwell, B. Superoxide-dependent formation of hydroxyl radicals and lipid peroxidation in the presence of iron salts. Detection of ╩╗catalytic╩╝ iron and anti-oxidant activity in extracelllar fluids, Biochem. 206, 605-609 (1982).
  168. 223. Wang, Y. X. Hussain, S. M. & Krestin, G. P. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging, Eur. Radiol. 11, 2319-2331 (2001).
  169. 206. Thorek, Daniel L J, Chen, A. K. Czupryna, J. & Tsourkas, A. Superparamagnetic iron oxide nanoparticle probes for molecular imaging, Ann. Biomed. Eng. 34, 23-38 (2006).
  170. 95. Ittrich, H. Peldschus, K. Raabe, N. Kaul, M. & Adam, G. Superparamagnetic iron oxide nanoparticles in biomedicine: applications and developments in diagnostics and therapy, RöFo : Fortschritte auf dem Gebiete der Röntgenstrahlen und der Nuklearmedizin 185, 1149-1166 (2013).
  171. 198. Taupitz, M. Schmitz, S. & Hamm, B. Superparamagnetische Eisenoxidpartikel: Aktueller Stand und zukünftige Entwicklungen, RöFo 175, 752-765 (2003).
  172. 188. Simon, G. H. et al. T1 and T2 relaxivity of intracellular and extracellular USPIO at 1.5T and 3T clinical MR scanning, Eur. Radiol. 16, 738-745 (2006).
  173. 33. Bulte, J. W. Laughlin, P. G. Jordan, E. K. Tran, V. A. Vymazal, J. & Frank J. A. Tagging of T cells with superparamagnetic iron oxide: uptake kinetics and relaxometry, Acad. Radiol. 3 Suppl 2, S301-3 (1996).
  174. 160. Qian, Z. M. Li, H. Sun, H. & Ho, K. Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway, Pharmacol. Rev. 54, 561-587 (2002).
  175. 124. Lewin, M. et al. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells, Nat. Biotechnol. 18, 410-414 (2000).
  176. 104. Josephson, L. Lewis, J. Jacobs, P. Hahn, P. F. & Stark, D. D. The effects of iron oxides on proton relaxivity, Magn. Reson. Imaging 6, 647-653 (1988).
  177. 61. Daigneault, M. Preston, J. A. Marriott, H. M. Whyte, Moira K B & Dockrell, D. H. The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages, PLoS ONE 5, e8668 (2010).
  178. 78. Henning, T. D. et al. The influence of ferucarbotran on the chondrogenesis of human mesenchymal stem cells, Contrast Media Mol. Imaging 4, 165-173 (2009a).
  179. 55. Chen Y.C. et al. The inhibitory effect of superparamagnetic iron oxide nanoparticle (Ferucarbotran) on osteogenic differentiation and its signaling mechanism in human mesenchymal stem cells, Toxicology And Applied Pharmacology (2010 Jun 1).
  180. 168. Richardson, D. R. & Ponka, P. The molecular mechanisms of the metabolism and transport of iron in normal and neoplastic cells, Biochim. Biophys. Acta 1331, 1-40 (1997).
  181. 89. Huang, D.-M. et al. The promotion of human mesenchymal stem cell proliferation by superparamagnetic iron oxide nanoparticles, Biomaterials 30, 3645-3651 (2009).
  182. 139. Min, Y. Akbulut, M. Kristiansen, K. Golan, Y. & Israelachvili, J. The role of interparticle and external forces in nanoparticle assembly, Nat. Mater. 7, 527-538 (2008).
  183. 151. Ogris, M. Steinlein, P. Kursa, M. Mechtler, K. Kircheis, R. & Wagner, E. The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells, Gene Ther. 5, 1425-1433 (1998).
  184. 177. Schäfer, R. et al. The use of clinically approved small particles of iron oxide (SPIO) for labeling of mesenchymal stem cells Aggravates Clinical Symptoms in Experimental Autoimmune Encephalomyelitis and Influences Their In Vivo Distribution, Cell Transplant. 17, 923-941 (2008).
  185. 71. Goodman, C. M. McCusker, C. D. Yilmaz, T. & Rotello, V. M. Toxicity of gold nanoparticles functionalized with cationic and anionic side chains, Bioconjug. Chem. 15, 897-900 (2004).
  186. 141. Montet-Abou, K. Montet, X. Weissleder, R. & Josephson, L. Transfection agent induced nanoparticle cell loading, Mol. Imaging 4, 165-171 (2005).
  187. 69. Freed, C. R. et al. Transplantation of embryonic dopamine neurons for severe Parkinson's disease, N Engl J Med 344, 710-719 (2001).
  188. 204. Thode, K. Müller, R. H. & Kresse, M. Two-time window and multiangle photon correlation spectroscopy size and zeta potential analysis--highly sensitive rapid assay for dispersion stability, Journal of pharmaceutical sciences 89, 1317-1324 (2000).
  189. 228. Weissleder, R. Elizondo, G. Wittenberg, J. Rabito, C. A. Bengele, H. H. & Josephson, L. Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging, Radiology 175, 489-493 (1990).
  190. 76. Heiland, S. Erb, G. Ziegler, S. & Krix, M. Where contrast agent concentration really matters - a comparison of CT and MRI, Invest. Radiol. 45, 529-537 (2010).


* Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten