Skip to main content

Advertisement

Log in

In Vivo Evaluation of Cerebral Transplantation of Resovist-Labeled Bone Marrow Stromal Cells in Parkinson’s Disease Rats Using Magnetic Resonance Imaging

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

The effectiveness of Resovist-labeled bone marrow stem cells (BMSCs) was evaluated in vivo following their cerebral transplantation in a model of Parkinson’s disease (PD) in rats using MRI, and the MRI findings were further compared with the behavior and histopathological manifestations of these rats. Forty PD rats were randomly assigned into five groups according to the cell doses injected into the rat brain site: control group (normal saline injection) and groups injected with 1 × 105, 1.5 × 105, 2 × 105, and 2.5 × 105 BMSCs. Gradient echo T2-weighted images were obtained immediately after cell transplantation and repeatedly taken 1, 4, 8, and 12 week(s) after cell transplantation. The rotational behavior of the animals was observed before and 1, 4, and 8 week(s) after transplantation. The rats were killed after the last MRI scanning, the brain tissues were analyzed by histopathology techniques, and RNAs were extracted for the expression analysis of selected genes using RT-PCR. One week following cell transplantation, all injected sites showed well-defined hypointense areas on MR images, with the most significant effect observed in rats injected with 2 × 105 BMSCs. These MR findings in PD rats lasted up to 12 weeks. The effectiveness of BMSC transplantation revealed by MRI was well confirmed by the behavioral and histopathological observations as well as indirectly supported by gene expression analyses. With the use of SPIO labeling, MRI techniques provided a dynamic evaluation of the spatial and temporal changes following cell transplantation and allowed the association analysis among the imaging, functions, and gene expression analysis in rats. These data also suggest the therapeutic potential of transplanted BMSCs. It is reasonable to speculate that the use of MRI in in vivo evaluation of the effect and fate of transplanted cells in various disease models will be beneficial to developing new strategies of cell-based gene therapy.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

BMSCs:

Bone marrow stem cells

MRI:

Magnetic resonance imaging

PD:

Parkinson’s disease

SPIO:

Superparamagnetic iron oxide

References

  1. Galvan, A., & Wichmann, T. (2008). Pathophysiology of Parkinsonism. Clinical Neurophysiology, 119, 1459–1474.

    Article  CAS  Google Scholar 

  2. Sanchez-Ramos, J., Song, S., Cardozo-Pelaez, F., Hazzi, C., Stedeford, T., Willing, A., et al. (2000). Adult bone marrow stromal cells differentiate into neural cells in vitro. Experimental Neurology, 164, 247–256.

    Article  CAS  Google Scholar 

  3. Daniela, F., Vescovi, A. L., & Bottai, D. (2007). The stem cells as a potential treatment for neurodegeneration. Methods in Molecular Biology, 399, 199–213.

    Article  Google Scholar 

  4. Woodbury, D., Schwarz, E. J., Prockop, D. J., & Black, I. B. (2000). Adult rat and human bone marrow stromal cells differentiate into neurons. Journal of Neuroscience Research, 61, 364–370.

    Article  CAS  Google Scholar 

  5. Li, Y., Chen, J., Wang, L., Zhang, L., Lu, M., & Chopp, M. (2001). Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neuroscience Letters, 316, 67–70.

    Article  CAS  Google Scholar 

  6. Strauer, B. E., & Kornowski, R. (2003). Stem cell therapy in perspective. Circulation, 107, 929–934.

    Article  Google Scholar 

  7. Read, E. J., Keenan, A. M., Carter, C. S., Yolles, P. S., & Davey, R. J. (1990). In vivo traffic of indium-111-oxine labeled human lymphocytes collected by automated apheresis. Journal of Nuclear Medicine, 31, 999–1006.

    CAS  Google Scholar 

  8. Corot, C., Robert, P., Idee, J. M., & Port, M. (2006). Recent advances in iron oxide nanocrystal technology for medical imaging. Advanced Drug Delivery Reviews, 58, 1471–1504.

    Article  CAS  Google Scholar 

  9. Jendelova, P., Herynek, V., Urdzikova, L., Glogarova, K., Kroupova, J., Andersson, B., et al. (2004). Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord. Journal of Neuroscience Research, 76, 232–243.

    Article  CAS  Google Scholar 

  10. Wang, Y. X., Hussain, S. M., & Krestin, G. P. (2001). Superparamagnetic iron oxide contrast agents: Physicochemical characteristics and applications in MR imaging. European Radiology, 11, 2319–2331.

    Article  CAS  Google Scholar 

  11. Reimer, P., & Tombach, B. (1998). Hepatic MRI with SPIO: Detection and characterization of focal liver lesions. European Radiology, 8, 1198–1204.

    Article  CAS  Google Scholar 

  12. Javazon, E. H., Colter, D. C., Schwarz, E. J., & Prockop, D. J. (2001). Rat marrow stromal cells are more sensitive to plating density and expand more rapidly from single-cell-derived colonies than human marrow stromal cells. Stem Cells, 19, 219–225.

    Article  CAS  Google Scholar 

  13. Colter, D. C., Sekiya, I., & Prockop, D. J. (2001). Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proceedings of the National Academy of Sciences of the United States of America, 98, 7841–7845.

    Article  CAS  Google Scholar 

  14. Fawwaz, R. A., Oluwole, S., Wang, T. S., Kuromoto, N., Iga, C., Hardy, M. A., et al. (1985). Biodistribution of radiolabeled lymphocytes. Radiology, 155, 483–486.

    CAS  Google Scholar 

  15. Schafer, R., Kehlbach, R., Wiskirchen, J., Bantleon, R., Pintaske, J., Brehm, B. R., et al. (2007). Transferrin receptor upregulation: In vitro labeling of rat mesenchymal stem cells with superparamagnetic iron oxide. Radiology, 244, 514–523.

    Article  Google Scholar 

  16. Sun, R., Dittrich, J., Le-Huu, M., Mueller, M. M., Bedke, J., Kartenbeck, J., et al. (2005). Physical and biological characterization of superparamagnetic iron oxide- and ultrasmall superparamagnetic iron oxide-labeled cells: A comparison. Investigative Radiology, 40, 504–513.

    Article  Google Scholar 

  17. Metz, S., Bonaterra, G., Rudelius, M., Settles, M., Rummeny, E. J., & Daldrup-Link, H. E. (2004). Capacity of human monocytes to phagocytose approved iron oxide MR contrast agents in vitro. European Radiology, 14, 1851–1858.

    Article  Google Scholar 

  18. Linker, R. A., Kroner, A., Horn, T., Gold, R., Maurer, M., & Bendszus, M. (2006). Iron particle-enhanced visualization of inflammatory central nervous system lesions by high resolution: Preliminary data in an animal model. AJNR. American Journal of Neuroradiology, 27, 1225–1229.

    CAS  Google Scholar 

  19. Henning, T. D., Boddington, S., & Daldrup-Link, H. E. (2008). Labeling hESCs and hMSCs with iron oxide nanoparticles for non-invasive in vivo tracking with MR imaging. Journal of Visualized Experiments, 31, 685. http://www.ncbi.nlm.nih.gov/pubmed/19066574.

  20. Hsiao, J. K., Tai, M. F., Chu, H. H., Chen, S. T., Li, H., Lai, D. M., et al. (2007). 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. Magnetic Resonance in Medicine, 58, 717–724.

    Article  CAS  Google Scholar 

  21. Wang, L., Deng, J., Wang, J., Xiang, B., Yang, T., Gruwel, M., et al. (2009). Superparamagnetic iron oxide does not affect the viability and function of adipose-derived stem cells, and superparamagnetic iron oxide-enhanced magnetic resonance imaging identifies viable cells. Magnetic Resonance Imaging, 27, 108–119.

    Article  CAS  Google Scholar 

  22. Bulte, J. W., Duncan, I. D., & Frank, J. A. (2002). In vivo magnetic resonance tracking of magnetically labeled cells after transplantation. Journal of Cerebral Blood Flow and Metabolism, 22, 899–907.

    Google Scholar 

  23. Guzman, R., Uchida, N., Bliss, T. M., He, D., Christopherson, K. K., Stellwagen, D., et al. (2007). Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proceedings of the National Academy of Sciences of the United States of America, 104, 10211–10216.

    Article  CAS  Google Scholar 

  24. George, A. J., Bhakoo, K. K., Haskard, D. O., Larkman, D. J., & Reynolds, P. R. (2006). Imaging molecular and cellular events in transplantation. Transplantation, 82, 1124–1129.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by the Natural science fund for colleges and universities in Jiangsu Province (no. 06KJB320097). Mr. Wenbing Li read this manuscript and gave some comments.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Jun-Kang Shen or Kai Li.

Additional information

Jing Guo and Jun-Kang Shen have contributed equally to this paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guo, J., Shen, JK., Wang, L. et al. In Vivo Evaluation of Cerebral Transplantation of Resovist-Labeled Bone Marrow Stromal Cells in Parkinson’s Disease Rats Using Magnetic Resonance Imaging. Appl Biochem Biotechnol 163, 636–648 (2011). https://doi.org/10.1007/s12010-010-9069-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-010-9069-y

Keywords

Navigation