Skip to main content
SpringerLink
Log in

Tracking of Administered Progenitor Cells in Brain Injury and Stroke by Magnetic Resonance Imaging

  • Chapter
  • First Online:
Cell Therapy for Brain Injury

Abstract

Traumatic brain injury and stroke remain important causes of chronic neurologic morbidity due to the lack of vasculature in injured brain. Promising data from preclinical and clinical studies suggest that transplantation of exogenous hematopoietic stem cells (HSCs) and neural progenitor cells (NPCs) has therapeutic potential for boosting brain repair. This neuroregeneration could be achieved by HSCs/NPCs migration, differentiation, enhanced endogenous angiogenesis and neurogenesis, and the secretion of trophic factors by these cells in injured tissue and stroke. The neuroregeneration is achieved by significant decrease in graft-versus-host disease and improved functional behavior of damaged brain. Importantly, these stem cells are derived from peripheral blood, umbilical cord blood (UCB), bone marrow (BM), and embryonic sources. A subpopulation of CD34+ human HSCs identified by the cell-surface molecule AC133 (CD133) has been shown to be more specific for endothelial differentiation and vascular repair. Similarly, NPCs have shown to induced angiogenesis and neurogenesis in stroke. Several studies have been exploited in vivo imaging modalities, importantly magnetic resonance imaging (MRI) to monitor the migration and engraftment efficacy of administered cells for cell-based therapies. This chapter covers the characterization of contrast agents, cell-labeling methods for MRI, use of endothelial progenitor cells (EPCs) and NPCs in vascular integrity and neuroregeneration, and molecular mechanisms of their homing to the injured or stroke site, such as their interaction with brain endothelium as depicted by MRI.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Yi BR, Kim SU, Choi KC. Development and application of neural stem cells for treating various human neurological diseases in animal models. Lab Anim Res. 2013;29(3):131–7.

    PubMed Central  PubMed  Google Scholar 

  2. Canazza A, et al. Experimental models of brain ischemia: a review of techniques, magnetic resonance imaging, and investigational cell-based therapies. Front Neurol. 2014;5:19.

    PubMed Central  PubMed  Google Scholar 

  3. Kalladka D, Muir KW. Brain repair: cell therapy in stroke. Stem Cells Cloning. 2014;7:31–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  4. Sanberg PR, et al. Advantages and challenges of alternative sources of adult-derived stem cells for brain repair in stroke. Prog Brain Res. 2012;201:99–117.

    PubMed  Google Scholar 

  5. Liu X, et al. Cell based therapies for ischemic stroke: from basic science to bedside. Prog Neurobiol. 2014;115:92–115.

    PubMed Central  PubMed  Google Scholar 

  6. Brazelton TR, Blau HM. Optimizing techniques for tracking transplanted stem cells in vivo. Stem Cells. 2005;23(9):1251–65.

    PubMed  Google Scholar 

  7. Blits B, et al. Lentiviral vector-mediated transduction of neural progenitor cells before implantation into injured spinal cord and brain to detect their migration, deliver neurotrophic factors and repair tissue. Restor Neurol Neurosci. 2005;23(5–6):313–24.

    CAS  PubMed  Google Scholar 

  8. Tanaka M, et al. In vivo visualization of cardiac allograft rejection and trafficking passenger leukocytes using bioluminescence imaging. Circulation. 2005;112 Suppl 9:I105–10.

    PubMed  Google Scholar 

  9. Paulmurugan R, Gambhir SS. Novel fusion protein approach for efficient high-throughput screening of small molecule-mediating protein-protein interactions in cells and living animals. Cancer Res. 2005;65(16):7413–20.

    PubMed Central  CAS  PubMed  Google Scholar 

  10. Paulmurugan R, Gambhir SS. Firefly luciferase enzyme fragment complementation for imaging in cells and living animals. Anal Chem. 2005;77(5):1295–302.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Bruchez MP. Turning all the lights on: quantum dots in cellular assays. Curr Opin Chem Biol. 2005;9(5):533–7.

    CAS  PubMed  Google Scholar 

  12. Akerman ME, et al. Nanocrystal targeting in vivo. Proc Natl Acad Sci U S A. 2002;99(20):12617–21.

    PubMed Central  CAS  PubMed  Google Scholar 

  13. Michalet X, et al. Quantum dots for live cells, in vivo imaging, and diagnostics. Science. 2005;307(5709):538–44.

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Potapova IA, et al. Mesenchymal stem cells support migration, extracellular matrix invasion, proliferation, and survival of endothelial cells in vitro. Stem Cells. 2007;25(7):1761–8.

    CAS  PubMed  Google Scholar 

  15. Rosen AB, et al. Finding fluorescent needles in the cardiac haystack: tracking human mesenchymal stem cells labeled with quantum dots for quantitative in vivo three-dimensional fluorescence analysis. Stem Cells. 2007;25(8):2128–38.

    CAS  PubMed  Google Scholar 

  16. Dingli D, et al. Combined I-124 positron emission tomography/computed tomography imaging of NIS gene expression in animal models of stably transfected and intravenously transfected tumor. Mol Imaging Biol. 2006;8(1):16–23.

    PubMed  Google Scholar 

  17. Kim DE, et al. Near-infrared fluorescent imaging of cerebral thrombi and blood-brain barrier disruption in a mouse model of cerebral venous sinus thrombosis. J Cereb Blood Flow Metab. 2005;25(2):226–33.

    PubMed  Google Scholar 

  18. Chung JK. Sodium iodidesymporter: its role in nuclear medicine. J Nucl Med. 2002;43(9):1188–200.

    CAS  PubMed  Google Scholar 

  19. Yaghoubi SS, et al. Imaging progress of herpes simplex virus type 1 thymidine kinase suicide gene therapy in living subjects with positron emission tomography. Cancer Gene Ther. 2005;12(3):329–39.

    CAS  PubMed  Google Scholar 

  20. Buursma AR, et al. 18F-FEAU as a radiotracer for herpes simplex virus thymidine kinase gene expression: in-vitro comparison with other PET tracers. Nucl Med Commun. 2006;27(1):25–30.

    CAS  PubMed  Google Scholar 

  21. Hustinx R, et al. Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and. Eur J Nucl Med. 2001;28(1):5–12.

    CAS  PubMed  Google Scholar 

  22. Cao F, et al. In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery. Circulation. 2006;113(7):1005–14.

    PubMed  Google Scholar 

  23. Zhang H, et al. Synthesis and evaluation of bombesin derivatives on the basis of pan-bombesin peptides labeled with indium-111, lutetium-177, and yttrium-90 for targeting bombesin receptor-expressing tumors. Cancer Res. 2004;64(18):6707–15.

    CAS  PubMed  Google Scholar 

  24. Love C, et al. Diagnosing infection in the failed joint replacement: a comparison of coincidence detection 18F-FDG and 111In-labeled leukocyte/99mTc-sulfur colloid marrow imaging. J Nucl Med. 2004;45(11):1864–71.

    PubMed  Google Scholar 

  25. Botti C, et al. Comparison of three different methods for radiolabelling human activated T lymphocytes. Eur J Nucl Med. 1997;24(5):497–504.

    CAS  PubMed  Google Scholar 

  26. Read EJ, et al. In vivo traffic of indium-111-oxine labeled human lymphocytes collected by automated apheresis. J Nucl Med. 1990;31(6):999–1006.

    CAS  PubMed  Google Scholar 

  27. Griffith KD, et al. In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma. J Natl Cancer Inst. 1989;81(22):1709–17.

    CAS  PubMed  Google Scholar 

  28. Fisher B, et al. Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma. J Clin Oncol. 1989;7(2):250–61.

    CAS  PubMed  Google Scholar 

  29. Adonai N, et al. Ex vivo cell labeling with 64Cu-pyruvaldehyde-bis(N4-methylthiosemicarbazone) for imaging cell trafficking in mice with positron-emission tomography. Proc Natl Acad Sci U S A. 2002;99(5):3030–5.

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Hofmann M, et al. Monitoring of bone marrow cell homing into the infarcted human myocardium. Circulation. 2005;111(17):2198–202.

    PubMed  Google Scholar 

  31. Frank JA, et al. Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents. Acad Radiol. 2002;9 Suppl 2:S484–7.

    PubMed  Google Scholar 

  32. Frank JA, et al. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology. 2003;228(2):480–7.

    PubMed  Google Scholar 

  33. Arbab AS, et al. Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. Blood. 2004;104(4):1217–23.

    CAS  PubMed  Google Scholar 

  34. Arbab AS, et al. Characterization of biophysical and metabolic properties of cells labeled with superparamagnetic iron oxide nanoparticles and transfection agent for cellular MR imaging. Radiology. 2003;229(3):838–46.

    PubMed  Google Scholar 

  35. Modo M, Hoehn M, Bulte JW. Cellular MR imaging. Mol Imaging. 2005;4(3):143–64.

    PubMed  Google Scholar 

  36. Bulte JW, et al. Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging. Methods Enzymol. 2004;386:275–99.

    CAS  PubMed  Google Scholar 

  37. Bulte JW, Kraitchman DL. Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed. 2004;17(7):484–99.

    CAS  PubMed  Google Scholar 

  38. Arbab AS, et al. Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation: methods and techniques. Transplantation. 2003;76(7):1123–30.

    CAS  PubMed  Google Scholar 

  39. Arbab AS, et al. In vivo trafficking and targeted delivery of magnetically labeled stem cells. Hum Gene Ther. 2004;15(4):351–60.

    CAS  PubMed  Google Scholar 

  40. Kircher MF, et al. A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation. Cancer Res. 2003;63(23):8122–5.

    CAS  PubMed  Google Scholar 

  41. Moore A, et al. Tracking the recruitment of diabetogenic CD8 + T-cells to the pancreas in real time. Diabetes. 2004;53(6):1459–66.

    CAS  PubMed  Google Scholar 

  42. Josephson L, et al. High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. Bioconjug Chem. 1999;10(2):186–91.

    CAS  PubMed  Google Scholar 

  43. Walczak P, et al. Instant MR labeling of stem cells using magnetoelectroporation. Magn Reson Med. 2005;54(4):769–74.

    CAS  PubMed  Google Scholar 

  44. Toyoda K, et al. Effective magnetic labeling of transplanted cells with HVJ-E for magnetic resonance imaging. Neuroreport. 2004;15(4):589–93.

    CAS  PubMed  Google Scholar 

  45. van den Bos EJ, et al. Improved efficacy of stem cell labeling for magnetic resonance imaging studies by the use of cationic liposomes. Cell Transplant. 2003;12(7):743–56.

    PubMed  Google Scholar 

  46. Shapiro EM, Skrtic S, Koretsky AP. Sizing it up: cellular MRI using micron-sized iron oxide particles. Magn Reson Med. 2005;53(2):329–38.

    PubMed  Google Scholar 

  47. Zheng H, et al. Novel potential neuroprotective agents with both iron chelating and amino acid-based derivatives targeting central nervous system neurons. Biochem Pharmacol. 2005;70(11):1642–52.

    CAS  PubMed  Google Scholar 

  48. Vuu K, et al. Gadolinium-rhodamine nanoparticles for cell labeling and tracking via magnetic resonance and optical imaging. Bioconjug Chem. 2005;16(4):995–9.

    CAS  PubMed  Google Scholar 

  49. Anderson SA, Lee KK, Frank JA. Gadolinium-fullerenol as a paramagnetic contrast agent for cellular imaging. Invest Radiol. 2006;41(3):332–8.

    PubMed  Google Scholar 

  50. Rudelius M, et al. Highly efficient paramagnetic labelling of embryonic and neuronal stem cells. Eur J Nucl Med Mol Imaging. 2003;30(7):1038–44.

    CAS  PubMed  Google Scholar 

  51. Aime S, et al. Targeting cells with MR imaging probes based on paramagnetic Gd(III) chelates. Curr Pharm Biotechnol. 2004;5(6):509–18.

    CAS  PubMed  Google Scholar 

  52. Aoki I, et al. Cell labeling for magnetic resonance imaging with the T1 agent manganese chloride. NMR Biomed. 2006;19(1):50–9.

    CAS  PubMed  Google Scholar 

  53. Crich SG, et al. Improved route for the visualization of stem cells labeled with a Gd-/Eu-chelate as dual (MRI and fluorescence) agent. Magn Reson Med. 2004;51(5):938–44.

    CAS  PubMed  Google Scholar 

  54. Crich SG, et al. Visualization through magnetic resonance imaging of DNA internalized following “in vivo” electroporation. Mol Imaging. 2005;4(1):7–17.

    PubMed  Google Scholar 

  55. Himmelreich U, et al. A responsive MRI contrast agent to monitor functional cell status. Neuroimage. 2006;32(3):1142–9.

    CAS  PubMed  Google Scholar 

  56. Giesel FL, et al. Gadofluorine m uptake in stem cells as a new magnetic resonance imaging tracking method: an in vitro and in vivo study. Invest Radiol. 2006;41(12):868–73.

    CAS  PubMed  Google Scholar 

  57. Modo M, et al. Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging. Neuroimage. 2002;17(2):803–11.

    PubMed  Google Scholar 

  58. Daldrup-Link HE, et al. Cell tracking with gadophrin-2: a bifunctional contrast agent for MR imaging, optical imaging, and fluorescence microscopy. Eur J Nucl Med Mol Imaging. 2004;31(9):1312–21.

    PubMed  Google Scholar 

  59. Su W, et al. Synthesis and cellular uptake of a MR contrast agent coupled to an antisense peptide nucleic acid-cell- penetrating peptide conjugate. Contrast Media Mol Imaging. 2007;2(1):42–9.

    CAS  PubMed  Google Scholar 

  60. Brekke C, et al. The in vitro effects of a bimodal contrast agent on cellular functions and relaxometry. NMR Biomed. 2007;20(2):77–89.

    CAS  PubMed  Google Scholar 

  61. Wolf GL, et al. Contrast agents for magnetic resonance imaging. Magn Reson Annu. 1985:231–66.

    Google Scholar 

  62. Mendonca-Dias MH, Gaggelli E, Lauterbur PC. Paramagnetic contrast agents in nuclear magnetic resonance medical imaging. Semin Nucl Med. 1983;13(4):364–76.

    CAS  PubMed  Google Scholar 

  63. Na HB, et al. Development of a T1 contrast agent for magnetic resonance imaging using MnO nanoparticles. Angew Chem Int Ed Engl. 2007;46(28):5397–401.

    CAS  PubMed  Google Scholar 

  64. Odaka K, et al. In vivo tracking of transplanted mononuclear cells using manganese-enhanced magnetic resonance imaging (MEMRI). PLoS ONE. 2011;6(10):e25487.

    PubMed Central  CAS  PubMed  Google Scholar 

  65. Wang YX, Hussain SM, Krestin GP. Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol. 2001;11(11):2319–31.

    CAS  PubMed  Google Scholar 

  66. Jung CW. Surface properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn Reson Imaging. 1995;13(5):675–91.

    CAS  PubMed  Google Scholar 

  67. Hogemann D, et al. Improvement of MRI probes to allow efficient detection of gene expression. Bioconjug Chem. 2000;11(6):941–6.

    CAS  PubMed  Google Scholar 

  68. Yeh TC, et al. Intracellular labeling of T-cells with superparamagnetic contrast agents. Magn Reson Med. 1993;30(5):617–25.

    CAS  PubMed  Google Scholar 

  69. Bulte JW, et al. Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nat Biotechnol. 2001;19(12):1141–7.

    CAS  PubMed  Google Scholar 

  70. Ittrich H, et al. Labeling of mesenchymal stem cells with different superparamagnetic particles of iron oxide and detectability with MRI at 3T. Rofo. 2005;177(8):1151–63.

    CAS  PubMed  Google Scholar 

  71. Mikhaylova M, Kim doK, Bobrysheva N, Osmolowsky M, Semenov V, Tsakalakos T, Muhammed M. Superparamagnetism of magnetite nanoparticles: dependence on surface modification. Langmuir. 2004;20(6):2472–7.

    CAS  PubMed  Google Scholar 

  72. Hawrylak N, et al. Nuclear magnetic resonance (NMR) imaging of iron oxide-labeled neural transplants. Exp Neurol. 1993;121(2):181–92.

    CAS  PubMed  Google Scholar 

  73. Yeh TC, et al. In vivo dynamic MRI tracking of rat T-cells labeled with superparamagnetic iron-oxide particles. Magn Reson Med. 1995;33(2):200–8.

    CAS  PubMed  Google Scholar 

  74. Shen TT, et al. Magnetically labeled secretin retains receptor affinity to pancreas acinar cells. Bioconjug Chem. 1996;7(3):311–6.

    CAS  PubMed  Google Scholar 

  75. Fleige G, et al. In vitro characterization of two different ultrasmall iron oxide particles for magnetic resonance cell tracking. Invest Radiol. 2002;37(9):482–8.

    CAS  PubMed  Google Scholar 

  76. Kaufman CL, et al. Superparamagnetic iron oxide particles transactivator protein-fluorescein isothiocyanate particle labeling for in vivo magnetic resonance imaging detection of cell migration: uptake and durability. Transplantation. 2003;76(7):1043–6.

    CAS  PubMed  Google Scholar 

  77. Koch AM, et al. Uptake and metabolism of a dual fluorochrome Tat-nanoparticle in HeLa cells. Bioconjug Chem. 2003;14(6):1115–21.

    CAS  PubMed  Google Scholar 

  78. Ho C, Hitchens TK. A non-invasive approach to detecting organ rejection by MRI: monitoring the accumulation of immune cells at the transplanted organ. Curr Pharm Biotechnol. 2004;5(6):551–66.

    CAS  PubMed  Google Scholar 

  79. Song H, Choi JS, Huh YM, Kim S, Jun YW, Suh JS, Cheon J. Surface modulation of magnetic nanocrystals in the development of highly efficient magnetic resonance probes for intracellular labeling. J Am Chem Soc. 2005;127(28):9992–3.

    CAS  PubMed  Google Scholar 

  80. Schulze E, Ferrucci, Jr JT, Poss K, Lapointe L, Bogdanova A, Weissleder R. Cellular uptake and trafficking of a prototypical magnetic iron oxide label in vitro. Invest Radiol. 1995;30(10):604–10.

    CAS  PubMed  Google Scholar 

  81. Bulte JW, et al. Monitoring stem cell therapy in vivo using magnetodendrimers as a new class of cellular MR contrast agents. Academic Radiology. 2002;9 Suppl 2:S332–5.

    PubMed  Google Scholar 

  82. Smirnov P, et al. In vivo cellular imaging of magnetically labeled hybridomas in the spleen with a 1.5-T clinical MRI system. Magn Reson Med. 2004;52(1):73–9.

    PubMed  Google Scholar 

  83. Riviere C, et al. Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for cell graft monitoring and quantitation. Radiology. 2005;235(3):959–67.

    PubMed  Google Scholar 

  84. Brillet PY, et al. Evaluation of tumoral enhancement by superparamagnetic iron oxide particles: comparative studies with ferumoxtran and anionic iron oxide nanoparticles. Eur Radiol. 2005;15(7):1369–77.

    PubMed  Google Scholar 

  85. Wilhelm C, et al. Intracellular uptake of anionic superparamagnetic nanoparticles as a function of their surface coating. Biomaterials. 2003;24(6):1001–11.

    CAS  PubMed  Google Scholar 

  86. Jung CW, Jacobs P. Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. Magn Reson Imaging. 1995;13(5):661–74.

    CAS  PubMed  Google Scholar 

  87. Balakrishnan VS, et al. Physicochemical properties of ferumoxytol, a new intravenous iron preparation. Eur J Clin Invest. 2009;39(6):489–96.

    CAS  PubMed  Google Scholar 

  88. Schwenk MH. Ferumoxytol. a new intravenous iron preparation for the treatment of iron deficiency anemia in patients with chronic kidney disease. Pharmacotherapy. 2010;30(1):70–9.

    CAS  PubMed  Google Scholar 

  89. Thu MS, et al. Self-assembling nanocomplexes by combining ferumoxytol, heparin and protamine for cell tracking by magnetic resonance imaging. Nat Med. 2012;18(3):463–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  90. Gutova M, et al. Magnetic resonance imaging tracking of ferumoxytol-labeled human neural stem cells: studies leading to clinical use. Stem Cells Transl Med. 2013;2(10):766–75.

    PubMed Central  CAS  PubMed  Google Scholar 

  91. Kalish H, et al. Combination of transfection agents and magnetic resonance contrast agents for cellular imaging: relationship between relaxivities, electrostatic forces, and chemical composition. Magn Reson Med. 2003;50(2):275–82.

    CAS  PubMed  Google Scholar 

  92. Taupitz M, Schmitz S, Hamm B. Superparamagnetic iron oxide particles: current state and future development. Rofo. 2003;175(6):752–65.

    CAS  PubMed  Google Scholar 

  93. Sato N, et al. Pharmacokinetics and enhancement patterns of macromolecular MR contrast agents with various sizes of polyamidoamine dendrimer cores. Magn Reson Med. 2001;46(6):1169–73.

    CAS  PubMed  Google Scholar 

  94. Yan GP, et al. Synthesis and evaluation of gadolinium complexes based on PAMAM as MRI contrast agents. J Pharm Pharmacol. 2005;57(3):351–7.

    CAS  PubMed  Google Scholar 

  95. Bryant LH Jr, et al. Synthesis and relaxometry of high-generation (G = 5, 7, 9, and 10) PAMAM dendrimer-DOTA-gadolinium chelates. J Magn Reson Imaging. 1999;9(2):348–52.

    PubMed  Google Scholar 

  96. Kobayashi H, et al. Macromolecular MRI contrast agents with small dendrimers: pharmacokinetic differences between sizes and cores. Bioconjug Chem. 2003;14(2):388–94.

    CAS  PubMed  Google Scholar 

  97. Dodd CH, et al. Normal T-cell response and in vivo magnetic resonance imaging of T cells loaded with HIV transactivator-peptide-derived superparamagnetic nanoparticles. J Immunol Methods. 2001;256(1–2):89–105.

    CAS  PubMed  Google Scholar 

  98. Moore A, et al. MRI of insulitis in autoimmune diabetes. Magn Reson Med. 2002;47(4):751–8.

    PubMed  Google Scholar 

  99. Kircher MF, et al. In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors. Cancer Res. 2003;63(20):6838–46.

    CAS  PubMed  Google Scholar 

  100. Josephson L, et al. Near-infrared fluorescent nanoparticles as combined MR/optical imaging probes. Bioconjug Chem. 2002;13(3):554–60.

    CAS  PubMed  Google Scholar 

  101. Moore A, et al. Human transferrin receptor gene as a marker gene for MR imaging. Radiology. 2001;221:244–250.

    CAS  PubMed  Google Scholar 

  102. Moore A, et al. Measuring transferrin receptor gene expression by NMR imaging. Biochim Biophys Acta. 1998;1402(3):239–49.

    CAS  PubMed  Google Scholar 

  103. Bulte JW, et al. Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. Proc Natl Acad Sci U S A. 1999;96(26):15256–61.

    PubMed Central  CAS  PubMed  Google Scholar 

  104. Bulte JW, et al. Specific MR imaging of human lymphocytes by monoclonal antibody-guided dextran-magnetite particles. Magn Reson Med. 1992;25(1):148–57.

    CAS  PubMed  Google Scholar 

  105. Ahrens ET, et al. Receptor-mediated endocytosis of iron-oxide particles provides efficient labeling of dendritic cells for in vivo MR imaging. Magn Reson Med. 2003;49(6):1006–13.

    CAS  PubMed  Google Scholar 

  106. Berry CC, et al. The influence of transferrin stabilised magnetic nanoparticles on human dermal fibroblasts in culture. Int J Pharm. 2004;269(1):211–25.

    CAS  PubMed  Google Scholar 

  107. Miyoshi S, Flexman JA, Cross DJ, Maravilla KR, Kim Y, Anzai Y, Oshima J, Minoshima S. Transfection of neuroprogenitor cells with iron nanoparticles for magnetic resonance imaging tracking: cell viability, differentiation, and intracellular localization. Mol Imaging Biol. 2005;7(4):1–10.

    Google Scholar 

  108. Song Y, et al. Magnetic resonance imaging using hemagglutinating virus of Japan-envelope vector successfully detects localization of intra-cardially administered microglia in normal mouse brain. Neurosci Lett. 2006;395(1):42–5.

    CAS  PubMed  Google Scholar 

  109. Hinds KA, et al. Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells. Blood. 2003;102(3):867–72.

    CAS  PubMed  Google Scholar 

  110. Hill JM, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation. 2003;108(8):1009–14.

    PubMed Central  PubMed  Google Scholar 

  111. Wu YL, et al. In situ labeling of immune cells with iron oxide particles: an approach to detect organ rejection by cellular MRI. Proc Natl Acad Sci U S A. 2006;103(6):1852–7.

    PubMed Central  CAS  PubMed  Google Scholar 

  112. Suzuki Y, et al. In vitro comparison of the biological effects of three transfection methods for magnetically labeling mouse embryonic stem cells with ferumoxides. Magn Reson Med. 2007;57(6):1173–9.

    CAS  PubMed  Google Scholar 

  113. 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. 2007;26(2):505–16.

    PubMed  Google Scholar 

  114. Montet-Abou K, et al. Transfection agent induced nanoparticle cell loading. Mol Imaging. 2005;4(3):165–71.

    PubMed  Google Scholar 

  115. Reynolds F, Weissleder R, Josephson L. Protamine as an efficient membrane-translocating peptide. Bioconjug Chem. 2005;16(5):1240–5.

    CAS  PubMed  Google Scholar 

  116. Wu YJ, et al. In vivo leukocyte labeling with intravenous ferumoxides/protamine sulfate complex and in vitro characterization for cellular magnetic resonance imaging. Am J Physiol Cell Physiol. 2007;293(5):C1698–708.

    CAS  PubMed  Google Scholar 

  117. Arbab AS, et al. Labeling of cells with ferumoxides-protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells. NMR Biomed. 2005;18(8):553–9.

    CAS  PubMed  Google Scholar 

  118. Guzman R, et al. Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proc Natl Acad Sci U S A. 2007;104(24):10211–6.

    PubMed Central  CAS  PubMed  Google Scholar 

  119. Janic B, et al. Optimization and validation of FePro cell labeling method. PLoS ONE. 2009;4(6):e5873.

    PubMed Central  PubMed  Google Scholar 

  120. Pawelczyk E, et al. Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging. NMR Biomed. 2006;19(5):581–92.

    CAS  PubMed  Google Scholar 

  121. Arbab AS, et al. A model of lysosomal metabolism of dextran coated superparamagnetic iron oxide (SPIO) nanoparticles: implications for cellular magnetic resonance imaging. NMR Biomed. 2005;18(6):383–9.

    CAS  PubMed  Google Scholar 

  122. Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol. 1995;11(1):73–91.

    CAS  PubMed  Google Scholar 

  123. Folkman J, Shing Y. Angiogenesis. J Biol Chem. 1992;267(16):10931–4.

    CAS  PubMed  Google Scholar 

  124. Ellis LM, et al. Overview of angiogenesis: biologic implications for antiangiogenic therapy. Semin Oncol. 2001; 28(5 Suppl 16):94–104.

    CAS  PubMed  Google Scholar 

  125. Zhang ZG, et al. Bone marrow-derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res. 2002;90(3):284–8.

    CAS  PubMed  Google Scholar 

  126. Asahara T, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275(5302):964–7.

    CAS  PubMed  Google Scholar 

  127. Gehling UM, et al. In vitro differentiation of endothelial cells from AC133-positive progenitor cells. Blood. 2000;95(10):3106–12.

    CAS  PubMed  Google Scholar 

  128. Janic B, et al. Human cord blood-derived AC133 + progenitor cells preserve endothelial progenitor characteristics after long term in vitro expansion. PLoS ONE. 2010;5(2):e9173.

    PubMed Central  PubMed  Google Scholar 

  129. Arbab AS, et al. Magnetic resonance imaging and confocal microscopy studies of magnetically labeled endothelial progenitor cells trafficking to sites of tumor angiogenesis. Stem Cells. 2006;24(3):671–8.

    CAS  PubMed  Google Scholar 

  130. Hladovec J. Circulating endothelial cells as a sign of vessel wall lesions. Physiol Bohemoslov. 1978;27(2):140–4.

    CAS  PubMed  Google Scholar 

  131. Peichev M, et al. Expression of VEGFR-2 and AC133 by circulating human CD34( + ) cells identifies a population of functional endothelial precursors. Blood. 2000;95(3):952–8.

    CAS  PubMed  Google Scholar 

  132. Khakoo AY, Finkel T. Endothelial progenitor cells. Annu Rev Med. 2005;56:79–101.

    CAS  PubMed  Google Scholar 

  133. Ingram DA, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood. 2004;104(9):2752–60.

    CAS  PubMed  Google Scholar 

  134. Janic B, Arbab AS. Cord blood endothelial progenitor cells as therapeutic and imaging probes. Imaging Med. 2012;4(4):477–90.

    PubMed Central  CAS  PubMed  Google Scholar 

  135. Duda DG, et al. A protocol for phenotypic detection and enumeration of circulating endothelial cells and circulating progenitor cells in human blood. Nat Protoc. 2007;2(4):805–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  136. Castillo-Melendez M, et al. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells. Front Neurosci. 2013;7:194.

    PubMed Central  PubMed  Google Scholar 

  137. Patel SD, et al. Hematopoietic progenitor cells and restenosis after carotid endarterectomy. Stroke. 2012;43(6):1663–5.

    PubMed  Google Scholar 

  138. Hristov M, Weber C. Endothelial progenitor cells in vascular repair and remodeling. Pharmacol Res. 2008;58(2):148–51.

    CAS  PubMed  Google Scholar 

  139. Zampetaki A, Kirton JP, Xu Q. Vascular repair by endothelial progenitor cells. Cardiovasc Res. 2008;78(3):413–21.

    CAS  PubMed  Google Scholar 

  140. Bogoslovsky T, et al. Circulating CD133 + CD34 + progenitor cells inversely correlate with soluble ICAM-1 in early ischemic stroke patients. J Transl Med. 2011;9:145.

    PubMed Central  CAS  PubMed  Google Scholar 

  141. Tsai NW, et al. The association between circulating endothelial progenitor cells and outcome in different subtypes of acute ischemic stroke. Clin Chim Acta. 2014;427:6–10.

    CAS  PubMed  Google Scholar 

  142. Marti-Fabregas J, et al. Endothelial progenitor cells in acute ischemic stroke. Brain Behav. 2013;3(6):649–55.

    PubMed Central  PubMed  Google Scholar 

  143. Fan Y, et al. A modified culture medium increases blastocyst formation and the efficiency of human embryonic stem cell derivation from poor-quality embryos. J Reprod Dev. 2010;56(5):533–9.

    CAS  PubMed  Google Scholar 

  144. Red-Horse K, et al. Endothelium-microenvironment interactions in the developing embryo and in the adult. Dev Cell. 2007;12(2):181–94.

    CAS  PubMed  Google Scholar 

  145. Ohta T, et al. Administration of ex vivo-expanded bone marrow-derived endothelial progenitor cells attenuates focal cerebral ischemia-reperfusion injury in rats. Neurosurgery. 2006;59(3):679–86; (discussion 679-86).

    PubMed  Google Scholar 

  146. Bogoslovsky T, et al. Endothelial progenitor cells correlate with lesion volume and growth in acute stroke. Neurology. 2010;75(23):2059–62.

    PubMed Central  CAS  PubMed  Google Scholar 

  147. Hayakawa K, et al. Astrocytic high-mobility group box 1 promotes endothelial progenitor cell-mediated neurovascular remodeling during stroke recovery. Proc Natl Acad Sci U S A. 2012;109(19):7505–10.

    PubMed Central  CAS  PubMed  Google Scholar 

  148. Iskander A, et al. Intravenous administration of human umbilical cord blood-derived ac133 + endothelial progenitor cells in rat stroke model reduces infarct volume: magnetic resonance imaging and histological findings. Stem Cells Transl Med. 2013;2(9):703–14.

    PubMed Central  CAS  PubMed  Google Scholar 

  149. Jiang Q, et al. MRI detects brain reorganization after human umbilical tissue-derived cells (hUTC) treatment of stroke in rat. PLoS ONE. 2012;7(8):e42845.

    PubMed Central  CAS  PubMed  Google Scholar 

  150. Fan Y, et al. Endothelial progenitor cell transplantation improves long-term stroke outcome in mice. Ann Neurol. 2010;67(4):488–97.

    PubMed Central  CAS  PubMed  Google Scholar 

  151. Lu C, et al. EPCs in vascular repair: how can we clear the hurdles between bench and bedside? Front Biosci (Landmark Ed). 2014;19:34–48.

    CAS  Google Scholar 

  152. Arbab AS, et al. Detection of migration of locally implanted AC133 + stem cells by cellular magnetic resonance imaging with histological findings. FASEB J. 2008;22(9):3234–46.

    PubMed Central  CAS  PubMed  Google Scholar 

  153. Finney MR, et al. Umbilical cord blood-selected CD133 + cells exhibit vasculogenic functionality in vitro and in vivo. CytoTherapy. 2010;12(1):67–78.

    CAS  PubMed  Google Scholar 

  154. Kioi M, et al. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest. 2010;120(3):694–705.

    PubMed Central  CAS  PubMed  Google Scholar 

  155. Shichinohe H, et al. Role of SDF-1/CXCR4 system in survival and migration of bone marrow stromal cells after transplantation into mice cerebral infarct. Brain Res. 2007;1183:138–47.

    CAS  PubMed  Google Scholar 

  156. Silverman MD, et al. Endothelial progenitor cell (EPC) recruitment in rheumatoid arthritis. FASEB J. 2007;21(5):A186–A6.

    Google Scholar 

  157. Guo AM, et al. The cytochrome P450 4A/F-20-hydroxyeicosatetraenoic acid system: a regulator of endothelial precursor cells derived from human umbilical cord blood. J Pharmacol Exp Ther. 2011;338(2):421–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  158. Chen C, et al. Effect of HMGB1 on the paracrine action of EPC promotes post-ischemic neovascularization in mice. Stem Cells. 2014;32(10):2679–89.

    CAS  PubMed  Google Scholar 

  159. Heissig B, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109(5):625–37.

    PubMed Central  CAS  PubMed  Google Scholar 

  160. Ceradini DJ, et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004;10(8):858–64. Epub 2004 Jul 4.

    CAS  PubMed  Google Scholar 

  161. Kollet O, et al. Rapid and efficient homing of human CD34( + )CD38(-/low)CXCR4( + ) stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) mice. Blood. 2001;97(10):3283–91.

    CAS  PubMed  Google Scholar 

  162. Hayakawa K, et al. Reactive astrocytes promote adhesive interactions between brain endothelium and endothelial progenitor cells via HMGB1 and beta-2 integrin signaling. Stem Cell Res. 2014;12(2):531–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  163. Paczkowska E, et al. Increased circulating endothelial progenitor cells in patients with haemorrhagic and ischaemic stroke: the role of endothelin-1. J Neurol Sci. 2013;325(1–2):90–9.

    CAS  PubMed  Google Scholar 

  164. Rosell A, et al. Factors secreted by endothelial progenitor cells enhance neurorepair responses after cerebral ischemia in mice. PLoS ONE. 2013;8(9):e73244.

    PubMed Central  CAS  PubMed  Google Scholar 

  165. Navarro-Sobrino M, et al. The angiogenic gene profile of circulating endothelial progenitor cells from ischemic stroke patients. Vasc Cell. 2013;5(1):3.

    PubMed Central  CAS  PubMed  Google Scholar 

  166. Varma NR, et al. Differential biodistribution of intravenously administered endothelial progenitor and cytotoxic T-cells in rat bearing orthotopic human glioma. BMC Med Imaging. 2013;13(1):17.

    PubMed Central  PubMed  Google Scholar 

  167. Janic B, et al. MRI tracking of FePro labeled fresh and cryopreserved long term in vitro expanded human cord blood AC133 + endothelial progenitor cells in rat glioma. PLOS ONE. 2012;7(5):e37577.

    PubMed Central  CAS  PubMed  Google Scholar 

  168. Varma NR, et al. Endothelial progenitor cells (EPCs) as gene carrier system for rat model of human glioma. PLoS ONE. 2012;7(1):e30310.

    PubMed Central  CAS  PubMed  Google Scholar 

  169. Gotts JE, Chesselet MF. Vascular changes in the subventricular zone after distal cortical lesions. Exp Neurol. 2005;194(1):139–50.

    PubMed  Google Scholar 

  170. Nakayama D, et al. Injury-induced neural stem/progenitor cells in post-stroke human cerebral cortex. Eur J Neurosci. 2010;31(1):90–8.

    PubMed  Google Scholar 

  171. Borlongan CV, et al. Bone marrow grafts restore cerebral blood flow and blood brain barrier in stroke rats. Brain Res. 2004;1010(1–2):108–16.

    CAS  PubMed  Google Scholar 

  172. Polezhaev LV, Alexandrova MA. Transplantation of embryonic brain tissue into the brain of adult rats after hypoxic hypoxia. J Hirnforsch. 1984;25(1):99–106.

    CAS  PubMed  Google Scholar 

  173. Polezhaev LV, et al. Morphological, biochemical and physiological changes in brain nervous tissue of adult intact and hypoxia-subjected rats after transplantation of embryonic nervous tissue. J Hirnforsch. 1985;26(3):281–9.

    CAS  PubMed  Google Scholar 

  174. Jiang Q, et al. MRI detects white matter reorganization after neural progenitor cell treatment of stroke. Neuroimage. 2006;32(3):1080–9.

    PubMed  Google Scholar 

  175. Li L, et al. Transplantation of marrow stromal cells restores cerebral blood flow and reduces cerebral atrophy in rats with traumatic brain injury: in vivo MRI study. J Neurotrauma. 2011;28(4):535–45.

    PubMed Central  PubMed  Google Scholar 

  176. Liu XS, et al. MicroRNA-17-92 cluster mediates the proliferation and survival of neural progenitor cells after stroke. J Biol Chem. 2013;288(18):12478–88.

    PubMed Central  CAS  PubMed  Google Scholar 

  177. Liu XS, et al. MicroRNA profiling in subventricular zone after stroke: MiR-124a regulates proliferation of neural progenitor cells through Notch signaling pathway. PLOS ONE. 2011;6(8):e23461.

    PubMed Central  CAS  PubMed  Google Scholar 

  178. Wang L, et al. The Notch pathway mediates expansion of a progenitor pool and neuronal differentiation in adult neural progenitor cells after stroke. Neuroscience. 2009;158(4):1356–63.

    PubMed Central  CAS  PubMed  Google Scholar 

  179. Bakondi B, et al. SDF-1alpha secreted by human CD133-derived multipotent stromal cells promotes neural progenitor cell survival through CXCR7. Stem Cells Dev. 2011;20(6):1021–9.

    PubMed Central  CAS  PubMed  Google Scholar 

  180. Zhu J, Zhou L, XingWu F. Tracking neural stem cells in patients with brain trauma. N Engl J Med. 2006;355(22):2376–8.

    CAS  PubMed  Google Scholar 

  181. Zhang ZG, et al. Magnetic resonance imaging and neurosphere therapy of stroke in rat. Ann Neurol. 2003;53(2):259–63.

    PubMed  Google Scholar 

  182. Zhang Z, et al. In vivo magnetic resonance imaging tracks adult neural progenitor cell targeting of brain tumor. Neuroimage. 2004;23(1):281–7.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Tumor Angiogenesis Laboratory, Department of Biochemistry and Molecular Biology, Cancer Center, Georgia Regents University, 1410 Laney Walker Blvd, 30912, Augusta, GA, USA

    Bhagelu R. Achyut PhD & Prof. Ali S. Arbab MD, PhD

Authors
  1. Bhagelu R. Achyut PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Prof. Ali S. Arbab MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ali S. Arbab MD, PhD .

Editor information

Editors and Affiliations

  1. Department of Neurology, Georgia Regents University, Augusta, Georgia, USA

    David C. Hess

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Achyut, B., Arbab, A. (2015). Tracking of Administered Progenitor Cells in Brain Injury and Stroke by Magnetic Resonance Imaging. In: Hess, D. (eds) Cell Therapy for Brain Injury. Springer, Cham. https://doi.org/10.1007/978-3-319-15063-5_12

Download citation

Publish with us

Policies and ethics

Search

Navigation