Skip to main content

Advertisement

SpringerLink
Log in

In vivo MR Imaging of Tissue-engineered Human Mesenchymal Stem Cells Transplanted to Mouse: a Preliminary Study

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

Current progress integrating stem cell biology and tissue engineering techniques has been invaluable to clinical applications. Prior to the application of celluar transplantation technique to patients, we need to establish techniques that can monitor their tissue biodistribution non-invasively. In this study, we proposed an imaging modality using MRI to not only monitor implanted scaffold in vivo, but also to track transplanted cells and behavior around the implant. For this purpose, human bone marrow-derived mesenchymal stem cells (hMSCs) were labeled with superparamagnetic iron oxide (Feridex) and then labeled hMSCs were cultured in a gelatin sponge used as a scaffold to support cell growth and proliferation. Histological assessment and MTT assay showed that cell labeling with MR contrast agent did not harm cell viability. Also, Feridex-labeled hMSCs showed a significant decrease in T2 signal intensity, even within the gelatin sponge in vitro. After implanting the sponge/cell complex in vivo, we could visualize cellular behavior around the implant over time using a noninvasive MRI modality and this finding was correlated with histological study, which illustrates the potential of a new approach proposed here for in vivo monitoring of implanted cell-based tissue-engineered product.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.
Figure 2.
Figure 3.
Figure 4.

References

  1. Aime S., Botta M., Garino E., Crich S. G., Giovenzana G., Pagliarin R., Palmisano G., Sisti M. (2000) Non-covalent conjugates between cationic polyamino acids and GdIII chelates: A route for seeking accumulation of MRI-contrast agents at tumor targeting sites. Chemistry 6: 2609–2617

    Article  CAS  PubMed  Google Scholar 

  2. Bianco P., Robey P. G. (2001) Stem cells in tissue engineering. Nature 414:118–121

    Article  CAS  PubMed  Google Scholar 

  3. Bull S. R., Guler M. O., Bras R. E., Venkatasubramanian P. N., Stupp S. I., Meade T. J. (2005) Magnetic resonance imaging of self-assembled biomaterial scaffolds. Bioconjug. Chem. 16: 1343-1348

    Article  CAS  PubMed  Google Scholar 

  4. Bulte J. W. M., Duncan I. D., Frank J. A. (2002) In vivo magnetic resonance tracking of magnetically labeled cells after transplantation. J. Cereb. Blood. Flow. Metab. 22: 899–907

    Article  PubMed  Google Scholar 

  5. Cortesini R. (2005) Stem cells, tissue engineering and organogenesis in transplantation. Transpl. Immunol. 15: 81–89

    Article  CAS  PubMed  Google Scholar 

  6. Dodd S. J., William M., Suhan J. P., William D. S., Koretsky A. P., Ho C. (1999) Detection of single mammalian cells by high-resolution magnetic resonance imaging. Biophys. J. 76:103–109

    Article  CAS  PubMed  Google Scholar 

  7. Foster-Gareau P., Heyn C., Alejski A., Rutt B.K.. (2003) Imaging single mammalian cells with a 1.5 T clinical MRI scanner. Magn. Res. Med. 49:968–971

    Article  Google Scholar 

  8. Genove G., DeMarco U., Xu H., Goins W. F., Ahrens E.T. (2005) A new trangene reporter for in vivo magnetic resonance imaging. Nat. Med. 11: 450–454

    Article  CAS  PubMed  Google Scholar 

  9. Hilderbrand S. A., Kelly K. A., Weissleder R., Tung C. H. (2005) Monofunctional near-infrared fluorochromes for imaging applications. Bioconjug. Chem. 16: 1275–1281

    Article  CAS  PubMed  Google Scholar 

  10. Huber M. M., Staubli A. B., Kustedjo K., Gray M. H., Shih J., Fraser S. E., Jacobs R. E., Meade T. J.. (1998) Fluorescently detectable magnetic resonance imaging agents. Bioconjug. Chem. 9: 242–249

    Article  CAS  PubMed  Google Scholar 

  11. Huh Y. M., Jun Y. W., Song H. T., Kim S., Choi J. S., Lee J. H., Yoon S., Kim K. S., Shin J. S., Suh J. S., Cheon J. (2005) In vivo magnetic resonance detection of cancer by using multifunctional magnetic nanocrystals. J. Am. Chem. Soc. 127:12387–12391

    Article  CAS  PubMed  Google Scholar 

  12. Jun Y. W., Huh Y. M., Choi J. S., Lee J. H., Song H. T., Kim S., Yoon S., Kim K. S., Shin J. S., Suh J. S., Cheon J.. (2005) Nanoscale size effect of magnetic nanocrystals and their utilization for cancer diagnosis via magnetic resonance imaging. J. Am. Chem. Soc. 127:5732–5733

    Article  CAS  PubMed  Google Scholar 

  13. Kotobuki N., Ioku K., Kawagoe D., Fujimori H., Goto S., Ohgushi H. (2005) Observation of osteogenic differentiation cascade of living mesenchymal stem cells on transparent hydroxyapatite ceramics. Biomaterials 26:779–785,

    Article  CAS  PubMed  Google Scholar 

  14. Langer R., Vacanti J. P. (1993) Tissue engineering. Science 260: 920–926

    Article  CAS  PubMed  Google Scholar 

  15. Lewin M., Carlesso N., Tung C. H., Tang X. W., Cory D., Scadden D. T., Weissleder R.. (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat. Biotechnol. 18: 410–414

    Article  CAS  PubMed  Google Scholar 

  16. Louie A. Y., Huber M. M., Ahrens E. T., Rothbacher U., Moats R., Jacobs R. E., Fraser S. E., Meade T. J. (2000) In vivo visualization of gene expression using magnetic resonance imaging. Nat. Biotechnol. 18: 321–325

    Article  CAS  PubMed  Google Scholar 

  17. Mader K., Bacic G., Domb A., Elmalak O., Langer R., Swartz H. M. (1997) Noninvasive in vivo monitoring of drug release and polymer erosion from biodegradable polymers by EPR spectroscopy and NMR imaging. J. Pharm. Sci. 86:126–134

    Article  CAS  PubMed  Google Scholar 

  18. Meade T. J., Taylor A. K., Bull S. R. (2003) New magnetic resonance contrast agents as biochemical reporters. Curr. Opin. Neurobiol. 13: 597–602

    Article  CAS  PubMed  Google Scholar 

  19. Nagaya N., Kangawa K., Itoh T., Iwase T., Murakami S., Miyahara Y., Fujii T., Uematsu M., Ohgushi H., Yamagishi M., Tokudome T., Mori H., Miyatake K., Kitamura S. (2005) Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation 112:1128–1135

    Article  PubMed  Google Scholar 

  20. Park K. I., Teng Y. D., Snyder E. Y. (2002) The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue. Nat. Biotechnol. 20:111–1117

    Article  CAS  Google Scholar 

  21. Pihlajamaki H., Kinnunen J., Bostman O. (1997) In vivo monitoring of the degradation process of bioresorbable polymeric implants using magnetic resonance imaging. Biomaterials 18: 1311–1315

    Article  CAS  PubMed  Google Scholar 

  22. Richardson T. P., Peters M. C., Ennett A. B., Mooney D. J. (2001) Polymeric system for dual growth factor delivery. Nat. Biotechnol. 19:1029–1034

    Article  CAS  PubMed  Google Scholar 

  23. Shapiro E. M., Skrtic S., Koretsky A. P. (2005) Sizing it up: Cellular MRI using micron-sized iron oxide particles. Magn. Reson. Med. 53:329–338

    Article  PubMed  Google Scholar 

  24. Shen F., Poncet-Legrand C., Somers S., Slade A., Yip C., Duft A. M., Winnik F. M., Chang P. L. (2003) Properties of a novel magnetized alginate for magnetic resonance imaging. Biotechnol. Bioeng. 83: 282–292

    Article  CAS  PubMed  Google Scholar 

  25. Song H. T., Choi J. S., Huh Y. M., Kim S., Jun Y. W., Suh J. S., Cheon J. (2005) Surface modulation of magnetic nanocrystals in the development of highly efficient magnetic resonance probes for intracellular labeling. J. Am. Chem. Soc. 127: 9992––9993

    Article  CAS  PubMed  Google Scholar 

  26. Uematsu K., Hattori K., Ishimoto Y., Yamauchi J., Habata T., Takakura Y., Ohgushi H., Fukuchi T., Sato M. (2005) Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold. Biomaterials 26:4273-4279

    Article  CAS  PubMed  Google Scholar 

  27. Vuu K., Xie J., McDonald M. A., Bernardo M., Hunter F., Zhang Y., Li K., Bednarski M., Guccione S.. (2005) Gadolinium–rhodamine nanoparticles for cell labeling and tracking via magnetic resonance and optical imaging. Bioconjug. Chem. 16: 995–999

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

We would like to thank to Prof. S.-H. Moon in Department of Orthopaedic Surgery in Yonsei University for his kind hMSC donation. This work was supported by the Korea Research Foundation Grant (KRF-2004-003-E00171).

Author information

Authors and Affiliations

  1. Department of radiology, College of Medicine, 134 ShinChon-Dong, Seodaemun-Ku, Seoul, 120-752, Republic of Korea

    In Kap Ko, Ho-Taek Song, Eun-Jin Cho, Eun Sook Lee, Yong-Min Huh & Jin-Suck Suh

Authors
  1. In Kap Ko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ho-Taek Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eun-Jin Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eun Sook Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong-Min Huh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jin-Suck Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yong-Min Huh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ko, I.K., Song, HT., Cho, EJ. et al. In vivo MR Imaging of Tissue-engineered Human Mesenchymal Stem Cells Transplanted to Mouse: a Preliminary Study. Ann Biomed Eng 35, 101–108 (2007). https://doi.org/10.1007/s10439-006-9204-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-006-9204-7

Keywords

Search

Navigation