Science China Life Sciences

, Volume 54, Issue 11, pp 981–987

Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging

  • ZhenHua Ren
  • JiaYin Wang
  • ChunLin Zou
  • YunQian Guan
  • Yu Alex Zhang
Open Access
Cover Article

Abstract

Recently, transplantation of allogeneic and autologous cells has been used for regenerative medicine. A critical issue is monitoring migration and homing of transplanted cells, as well as engraftment efficiency and functional capability in vivo. Monitoring of superparamagnetic iron oxide (SPIO) particles by magnetic resonance imaging (MRI) has been used in animal models and clinical settings to track labeled cells. A major limitation of MRI is that the signals do not show biological characteristics of transplanted cells in vivo. Bone marrow mesenchymal stem cells (MSCs) have been extensively investigated for their various therapeutic properties, and exhibit the potential to differentiate into cells of diverse lineages. In this study, cynomolgus monkey MSCs (cMSCs) were labeled with Molday ION Rhodamine-B™ (MIRB), a new SPIO agent, to investigate and characterize the biophysical and MRI properties of labeled cMSCs in vitro and in vivo. The results indicate that MIRB is biocompatible and useful for cMSCs labeling and cell tracking by multimodality imaging. Our method is helpful for detection of transplanted stem cells in vivo, which is required for understanding mechanisms of cell therapy.

Keywords

bone marrow mesenchymal stem cells MRI Molday ION Rhodamine-B™ transplantation nonhuman primate 

References

  1. 1.
    Caplan A I. Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics. Tissue Eng, 2005, 11: 1198–1211PubMedCrossRefGoogle Scholar
  2. 2.
    Dyson S C, Barker R A. Cell-based therapies for Parkinson’s disease. Expert Rev Neurother, 2011, 11: 831–844PubMedCrossRefGoogle Scholar
  3. 3.
    Raikwar S P, Zavazava N. Spontaneous in vivo differentiation of embryonic stem cell-derived pancreatic endoderm-like cells corrects hyperglycemia in diabetic mice. Transplantation, 2011, 91: 11–20PubMedCrossRefGoogle Scholar
  4. 4.
    Bussolati B, Camussi G. Adult stem cells and renal repair. J Nephrol, 2006, 19: 706–709PubMedGoogle Scholar
  5. 5.
    Daldrup-Link H E, Rudelius M, Piontek G, et al. Migration of iron oxide-labeled human hematopoietic progenitor cells in a mouse model: in vivo monitoring with 1.5-T MR imaging equipment. Radiology, 2005, 234: 197–205PubMedCrossRefGoogle Scholar
  6. 6.
    Budde M D, Frank J A. Magnetic tagging of therapeutic cells for MRI. J Null Med, 2009, 50: 171–174Google Scholar
  7. 7.
    Adler E D, Bystrup A, Briley-Saebo K C, et al. In vivo detection of embryonic stem cell-derived cardiovascular progenitor cells using Cy3-labeled GadofluorineM in murine myocardium. JACC Cardiovasc Imag, 2009, 2: 1114–1122CrossRefGoogle Scholar
  8. 8.
    Guzman R, Uchida N, Bliss TM, et al. Long-term monitoring of transplanted human neural stem cells in developmental and pathological contexts with MRI. Proc Natl Acad Sci USA, 2007, 104: 10211–10216PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Higuchi T, Anton M, Dumler K, et al. Combined reporter gene PET and iron oxide MRI for monitoring survival and localization of transplanted cells in the rat heart. J Nucl Med, 2009, 50: 1088–1094PubMedCrossRefGoogle Scholar
  10. 10.
    Chang N K, Jeong Y Y, Park J S, et al. Tracking of neural stem cells in rats with intracerebral hemorrhage by the use of 3T MRI. Korean J Radiol, 2008, 9: 196–204PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Onda T, Honmou O, Harada K, et al. Therapeutic benefits by human mesenchymal stem cells (hMSCs) and Ang-1 gene-modified hMSCs after cerebral ischemia. J Cereb Blood Flow Metab, 2008, 28: 329–340PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Cai J, Zhang X, Wang X, et al. In vivo MR imaging of magnetically labeled mesenchymal stem cells transplanted into rat liver through hepatic arterial injection. Contrast Media Mol Imag, 2008, 3: 61–66CrossRefGoogle Scholar
  13. 13.
    Kim D, Chun B G, Kim Y K, et al. In vivo tracking of human mesenchymal stem cells in experimental stroke. Cell Transplant, 2008, 16: 1007–1012PubMedCrossRefGoogle Scholar
  14. 14.
    Lu C W, Hung Y, Hsiao J K, et al. Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling. Nano Lett, 2007, 7: 149–154PubMedCrossRefGoogle Scholar
  15. 15.
    Mulder W J, Koole R, Brandwijk R J, et al. Quantum dots with a paramagnetic coating as a bimodal molecular imaging probe. Nano Lett, 2006, 6: 1–6PubMedCrossRefGoogle Scholar
  16. 16.
    Sung C K, Hong K A, Lin S, et al. Dual-modal nanoprobes for imaging of mesenchymal stem cell transplant by MRI and fluorescence imaging. Korean J Radiol, 2009, 10: 613–622PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Addicott B, Willman M, Rodriguez J, et al. Mesenchymal stem cell labeling and in vitro MR characterization at 1.5 T of new SPIO contrast agent: Molday ION Rhodamine-B™. Contrast Media Mol Imaging, 2011, 6: 7–18PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Emborg M E, Ebert A D, Moirano J, et al. GDNF-secreting human neural progenitor cells increase tyrosine hydroxylase and VMAT2 expression in MPTP-treated cynomolgus monkeys. Cell Transplant, 2008, 17: 383–395PubMedGoogle Scholar
  19. 19.
    Kim S H, Lee W J, Lim H K, et al. SPIO-enhanced MRI findings of well-differentiated hepatocellular carcinomas: correlation with MDCT findings. Korean J Radiol, 2009, 10: 112–120PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Satija N K, Singh V K, Verma Y K, et al. Mesenchymal stem cell-based therapy: a new paradigm in regenerative medicine. J Cell Mol Med, 2009, 13: 4385–402PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Wagner J, Kean T, Young R, et al. Optimizing mesenchymal stem cell-based therapeutics. Curr Opin Biotechnol, 2009, 20: 531–536PubMedCrossRefGoogle Scholar
  22. 22.
    Summer R, Fine A. Mesenchymal progenitor cell research: limitations and recommendations. Proc Am Thorac Soc, 2008, 5: 707–710PubMedCrossRefGoogle Scholar
  23. 23.
    Lee J W, Fang X, Krasnodembskaya A, et al. Concise review: mesenchymal stem cells for acute lung injury: Role of paracrine soluble factors. Stem Cells, 2011, 29: 913–919PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Bussolati B, Tetta C, Camussi G. Contribution of stem cells to kidney repair. Am J Nephrol, 2008, 28: 813–822PubMedCrossRefGoogle Scholar
  25. 25.
    Fattahi H, Laurent S, Liu F, et al. Magnetoliposomes as multimodal contrast agents for molecular imaging and cancer nanotheragnostics. Nanomedicine (Lond), 2011, 6: 529–544CrossRefGoogle Scholar
  26. 26.
    Fan C, Gao W, Chen Z, et al. Tumor selectivity of stealth multifunctionalized superparamagnetic iron oxide nanoparticles. Int J Pharm, 2011, 404: 180–190PubMedCrossRefGoogle Scholar
  27. 27.
    Bulte J W. In vivo MRI cell tracking: clinical studies. AJR Am J Roentgenol, 2009, 193: 314–325PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Kedziorek D A, Kraitchman D L. Superparamagnetic iron oxide labeling of stem cells for MRI tracking and delivery in cardiovascular disease. Methods Mol Biol, 2010, 660: 171–183PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Wagner J, Kean T, Young R, et al. Optimizing mesenchymal stem cell-based therapeutics. Curr Opin Biotechnol, 2009, 20: 531–536PubMedCrossRefGoogle Scholar
  30. 30.
    Karussis D, Karageorgiou C, Vaknin-Dembinsky A, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol, 2010, 67: 1187–1194PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Addicott B, Willman M, Rodriguez J, et al. Mesenchymal stem cell labeling and in vitro MR characterization at 1.5 T of new SPIO contrast agent: Molday ION Rhodamine-B™. Contrast Media Mol Imaging, 2011, 6: 7–18PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Frank J A, Miller B R, Arbab A S, et al. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology, 2003, 228: 480–487PubMedCrossRefGoogle Scholar
  33. 33.
    Song M, Moon W K, Kim Y, et al. 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 tat-CLIO. Korean J Radiol, 2007, 8: 365–371PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Hill J M, Dick A J, Raman V K, et al. Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation, 2003, 108: 1009–1014PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Chang J S, Chang K L, Hwang D F, et al. In vitro cytotoxicitiy of silica nanoparticles at high concentrations strongly depends on the metabolic activity type of the cell line. Environ Sci Technol, 2007, 41: 2064–2068PubMedCrossRefGoogle Scholar
  36. 36.
    Huang H, Xie Q, Kang M, et al. Labeling transplanted mice islet with polyvinylpyrrolidone coated superparamagnetic iron oxide nanoparticles for in vivo detection by magnetic resonance imaging. Nanotechnology, 2009, 20: 365101PubMedCrossRefGoogle Scholar
  37. 37.
    So P W, Kalber T, Hunt D, 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, 2010, 19: 419–429PubMedCrossRefGoogle Scholar
  38. 38.
    Mainenti P P, Mancini M, Mainolfi C, et al. Detection of colo-rectal liver metastases: prospective comparison of contrast enhanced US, multidetector CT, PET/CT, and 1.5 Tesla MR with extracellular and reticulo-endothelial cell specific contrast agents. Abdom Imaging, 2010, 35: 511–521PubMedCrossRefGoogle Scholar
  39. 39.
    Yoon T J, Yu K N, Kim E, et al. Specific targeting, cell sorting, and bioimaging with smart magnetic silica core-shell nanomaterials. Small, 2006, 2: 209–215PubMedCrossRefGoogle Scholar
  40. 40.
    Lu C W, Hung Y, Hsiao J K, et al. Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling. Nano Lett, 2007, 7: 149–154PubMedCrossRefGoogle Scholar
  41. 41.
    Veiseh O, Sun C, Gunn J, et al. Optical and MRI multifunctional nanoprobe for targeting gliomas. Nano Lett, 2005, 5: 1003–1008PubMedCrossRefGoogle Scholar
  42. 42.
    Kim J S, Yoon T J, Kim H K, et al. Sentinel lymph node mapping of the stomach using fluorescent magnetic nanoparticles in rabbits. Korean J Gastroenterol, 2008, 51: 19–24PubMedGoogle Scholar
  43. 43.
    Weissleder R. A clearer vision for in vivo imaging. Nat Biotechnol, 2001, 19: 316–317PubMedCrossRefGoogle Scholar

Copyright information

© The Author(s) 2011

This article is published under license to BioMed Central Ltd. Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  • ZhenHua Ren
    • 1
    • 2
  • JiaYin Wang
    • 1
  • ChunLin Zou
    • 1
  • YunQian Guan
    • 1
  • Yu Alex Zhang
    • 1
  1. 1.Cell Therapy Center, Xuanwu HospitalCapital Medical University, and Key Laboratory of Neurodegeneration, Ministry of EducationBeijingChina
  2. 2.Department of AnatomyAnhui Medical UniversityHefeiChina

Personalised recommendations