Stem Cell Reviews

, Volume 3, Issue 4, pp 265–269

Cell Tracing Techniques in Stem Cell Transplantation

  • Li Yan
  • Ying Han
  • Yuanlong He
  • Huahong Xie
  • Jingmei Liu
  • Lina Zhao
  • Jingbo Wang
  • Liuchun Gao
  • Daiming Fan


Pluripotent stem cells have shown great therapeutic promise because of their natural capacity to regenerate damaged tissue. Likewise, autologous stem cells or genetically modified stem cells have already been successfully applied in animal or clinical experimental studies including cardiopathy, diabetic disease, system lupus erythema, pancreatic disease, and liver disease. In these studies regarding stem cell transplants in different diseases, identifying the location of implanted cells and distinguishing them from endogenous cells is the first and most important step. Moreover, different tracing techniques were applied in different studies for their different sensitivity, dynamic range, convenience and reliability of their assays. Therefore, we will here review different tracing techniques and their applications in stem cell transplants, including both experiment studies and preclinical trials.


Stem cells Transplants Tracing techniques 


  1. 1.
    Petersen, B. E., Bowen, W. C., Patrene, K. D., Mars, W. M., Sullivan, A. K., Murase, N., et al. (1999). Bone marrow as a potential source of hepatic oval cells. Science, 284, 1168–1170.PubMedCrossRefGoogle Scholar
  2. 2.
    Theise, N. D., Nimmakayalu, M., Gardner, R., Illei, P. B., Morgan, G., Teperman, L., et al. (2000). Liver from bone marrow in humans. Hepatology, 32, 11–16.PubMedCrossRefGoogle Scholar
  3. 3.
    Alison, M. R., Poulsom, R., Jeffery, R., Dhillon, A. P., Quaglia, A., Jacob, J., et al. (2000). Hepatocytes from non-hepatic adult stem cells. Nature, 406, 257.PubMedCrossRefGoogle Scholar
  4. 4.
    Li, Y., Chen, J., Wang, L., Lu, M., & Chopp, M. (2001). Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology, 56, 1666–1672.PubMedGoogle Scholar
  5. 5.
    Ferrari, G., Cusella-De, Angelis, G., Coletta, M., Paolucci, E., Stornaiuolo, A., Cossu, G., et al. (1998). Muscle regeneration by bone marrow-derived myogenic progenitors. Science, 279, 1528–1530.PubMedCrossRefGoogle Scholar
  6. 6.
    Korbling, M., Katz, R. L., Khanna, A., Ruifrok, A. C., Rondon, G., Albitar, M., et al. (2002). Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. New England Journal of Medicine, 346, 738–746.PubMedCrossRefGoogle Scholar
  7. 7.
    Dalakas, E., Newsome, P. N., Harrison, D. J., & Plevris, J. N. (2005). Hematopoietic stem cell trafficking in liver injury. FASEB Journal, 19, 1225–1231.PubMedCrossRefGoogle Scholar
  8. 8.
    Kopen, G. C., Preckop, D. J., & Phinney, D. G. (1999). Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proceedings of the National Academy of Sciences of the United States of America, 96, 10711–10716.PubMedCrossRefGoogle Scholar
  9. 9.
    Chen, J., Li, Y., & Chopp, M. (2000). Intracerebral transplantation of bone marrow with BDNF after MCAo in rat. Neurepharmacology, 39, 711.CrossRefGoogle Scholar
  10. 10.
    Kiel, M. J., He, S., Ashkenazi, R., Gentry, S. N., Teta, M., Kushner, J. A., et al. (2007). Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature, 449, 238–242.PubMedCrossRefGoogle Scholar
  11. 11.
    Hou, M., Yang, K. M., Zhang, H., Zhu, W. Q., Duan, F. J., Wang, H., et al. (2007). Transplantation of mesenchymal stem cells from human bone marrow improves damaged heart function in rats. International Journal of Cardiology, 115, 220–228.PubMedCrossRefGoogle Scholar
  12. 12.
    Fu, X. B., Fang, L. J., Wang, Y. X., Sun, T. Z., & Cheng, B. (2004). Enhancing the repair quality of skin injury on porcine after autografting with the bone marrow mesenchymal stem cells. Chinese Journal of Medicine, 84, 920–924.Google Scholar
  13. 13.
    Munoz, J. R., Stoutenger, B. R., Robinson, A. P., Spees, J. L., & Prockop, D. J. (2005). Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proceedings of the National Academy of Sciences of the United States of America, 102, 18171–18176.PubMedCrossRefGoogle Scholar
  14. 14.
    Best, D. H., & Coleman, W. B. (2007). Cells of origin of small hepatocyte-like progenitor cells in the retrorsine model of rat liver injury and regeneration. Journal of Hepatology, 46, 1055–1063.PubMedCrossRefGoogle Scholar
  15. 15.
    Hemmrich, K., Meersch, M., von Heimburg, D., & Pallua, N. (2006). Applicability of the dyes CFSE, CM-DiI and PKH26 for tracking of human preadipocytes to evaluate adipose tissue engineering. Cells Tissues Organs, 184, 117–127.PubMedCrossRefGoogle Scholar
  16. 16.
    Hendrikx, P. J., Martens, C. M., Hagenbeek, A., Keij, J. F., & Visser, J. W. (1996). Homing of fluorescently labeled murine hematopoietic stem cells. Experimental Hematology, 24, 129–140.PubMedGoogle Scholar
  17. 17.
    Ford, J. W., Welling, T. H., Stanley, J. C., & Messina, L. M. (1996). PKH26 and 1251-PKH95: characterization and efficacy as labels for in vitro and in vivo endothelial cell localization and tracking. Journal of Surgical Research, 62, 23–28.PubMedCrossRefGoogle Scholar
  18. 18.
    Svilvassy, S. J., Meyerrose, T. E., Ragland, P. L., & Grimes, B. (2001). Differential homing and engraftment properties of hematopoietic progenitor cells from murine bone marrow, mobilized peripheral blood, and fetal liver. Blood, 98, 2108–2115.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhan, Y., Wang, Y., Wei, L., Chen, H., Cong, X., Fei, R., et al. (2006). Differentiation of hematopoietic stem cells into hepatocytes in liver fibrosis in rats. Transplantation Proceedings, 38, 3082–3085.PubMedCrossRefGoogle Scholar
  20. 20.
    Canola, K., Angenieux, B., Tekaya, M., Quiambao, A., Naash, M. I., Munier, F. L., et al. (2007). Retinal stem cells transplanted into models of late stages of retinitis pigmentosa preferentially adopt a glial or a retinal ganglion cell fate. Investigative Ophthalmology and Visual Science, 48, 446–454.PubMedCrossRefGoogle Scholar
  21. 21.
    Boomsma, R. A, Swaminathan, P. D., & Geenen, D. L. (2007). Intravenously injected mesenchymal stem cells home to viable myocardium after coronary occlusion and preserve systolic function without altering infarct size. International Journal of Cardiology, 122, 17–28.PubMedCrossRefGoogle Scholar
  22. 22.
    Brzóska, E., Grabowska, I., Hoser, G., Stremińska, W., Wasilewska, D., Machaj, E. K., et al. (2006). Participation of stem cells from human cord blood in skeletal muscle regeneration of SCID mice. Experimental Hematology, 34, 1262–1270.PubMedCrossRefGoogle Scholar
  23. 23.
    Chu, K., Park, K. I., Lee, S. T., Jung, K. H., Ko, S. Y., Kang, L., et al. (2005). Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia. Neuroscience Research, 53, 384–390.PubMedCrossRefGoogle Scholar
  24. 24.
    Parish, C. R. (1999). Fluorescent dyes for lymphocyte migration and proliferation studies. Immunology and Cell Biology, 77, 499–508.PubMedCrossRefGoogle Scholar
  25. 25.
    Shimomura, O., Johnson, F. H., & Saiga, Y. (1962). Extraction, purification and properties of aequorin, a bioluminescent protein from the luminous hydromedusan, Aequorea. Journal of Cellular and Comparative Physiology, 59, 223–239.PubMedCrossRefGoogle Scholar
  26. 26.
    Yoo, T. H., Link, A. J., & Tirrell, D. A. (2007). Evolution of a fluorinated green fluorescent protein. Proceedings of the National Academy of Sciences of the United States of America, 104, 13887–13890.PubMedCrossRefGoogle Scholar
  27. 27.
    Beaudry, P., Hida, Y., Udagawa, T., Alwayn, I. P., Greene, A. K., Arsenault, D., et al. (2007). Evolution of a fluorinated green fluorescent protein. Journal of Pediatric Surgery, 42, 1190–1198.PubMedCrossRefGoogle Scholar
  28. 28.
    Zhang, S., Zou, Z., Jiang, X., Xu, R., Zhang, W., Zhou, Y., et-al (2007). The therapeutic effects of tyrosine hydroxylase gene transfected hematopoetic stem cells in a rat model of Parkinson’s disease. Cellular and Molecular Neurobiology (in press), Aug 23.Google Scholar
  29. 29.
    Dai, W., Field, L. J., Rubart, M., Reuter, S., Hale, S. L., Zweigerdt, R., et al. (2007). Survival and maturation of human embryonic stem cell-derived cardiomyocytes in rat hearts. Journal of Molecular and Cellular Cardiology, 43, 504–516.PubMedCrossRefGoogle Scholar
  30. 30.
    Fujita, J., Mori, M., Kawada, H., Ieda, Y., Tsuma, M., Matsuzaki, Y., et-al. (2007). Administration of granulocyte colony-stimulating factor after myocardial infarction enhances the recruitment of hematopoietic stem cell-derived myofibroblasts and contributes to cardiac repair. Stem Cells (in press), Aug 9.Google Scholar
  31. 31.
    Li, Y., Atmaca-Sonmez, P., Schanie, C. L., Ildstad, S. T., Kaplan, H. J., & Enzmann, V. (2007). Endogenous bone marrow derived cells express retinal pigment epithelium cell markers and migrate to focal areas of RPE damage. Investigative Ophthalmology and Visual Science, 48, 4321–4327.PubMedCrossRefGoogle Scholar
  32. 32.
    Falanga, V., Iwamoto, S., Chartier, M., Yufit, T., Butmarc, J., Kouttab, N., et al. (2007). Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Engineering, 13, 1299–1312.PubMedCrossRefGoogle Scholar
  33. 33.
    Jeong, S. W., Chu, K., Jung, K. H., Kim, S. U., Kim, M., & Roh, J. K. (2003). Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke, 34, 2258–2263.PubMedCrossRefGoogle Scholar
  34. 34.
    Dragoo, J. L., Carlson, G., McCormick, F., Khan-Farooqi, H., Zhu, M., Zuk, P. A., et al. (2007). Healing full-thickness cartilage defects using adipose-derived stem cells. Tissue Engineering, 13, 1615–1621.PubMedCrossRefGoogle Scholar
  35. 35.
    Doi, K., Nibu, K., Ishida, H., Okado, H., & Terashima, T. (2005). Adenovirus-mediated gene transfer in olfactory epithelium and olfactory bulb: A long-term study. Annals of Otology, Rhinology & Laryngology, 114, 629–633.Google Scholar
  36. 36.
    Crain, B. J., Tran, S. D., & Mezey, E. (2005). Transplanted human bone marrow cells generate new brain cells. Journal of the Neurological Sciences, 233, 121–123.PubMedCrossRefGoogle Scholar
  37. 37.
    Jiang, W., Ma, A., Wang, T., Han, K., Liu, Y., Zhang, Y., et al. (2006). Intravenous transplantation of mesenchymal stem cells improves cardiac performance after acute myocardial ischemia in female rats. Transplant International, 19, 570–580.PubMedCrossRefGoogle Scholar
  38. 38.
    Kudo, K., Abe, Y., Hu, D. L., Kijima, H., & Nakane, A. (2007). Colonization and differentiation of transplanted embryonic stem cells in the irradiated intestine of mice. Tohoku Journal of Experimental Medicine, 212, 143–150.PubMedCrossRefGoogle Scholar
  39. 39.
    Deng, W., Han, Q., Liao, L., Li, C., Ge, W., Zhao, Z., et al. (2005). Engrafted bone marrow-derived flk-(1+) mesenchymal stem cells regenerate skin tissue. Tissue Engineering, 11, 110–119.PubMedCrossRefGoogle Scholar
  40. 40.
    Modo, M., Cash, D., Mellodew, K., Williams, S. C., Fraser, S. E., Meade, T. J., et al. (2002). Tracking transplanted stem cell migration using bifunctional, contrast agent-enhanced, magnetic resonance imaging. Neuroimage, 17, 803–811.PubMedCrossRefGoogle Scholar
  41. 41.
    Amsalem, Y., Mardor, Y., Feinberg, M. S., Landa, N., Miller, L., Daniels, D., et al. (2007). Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. Circulation, 116, 138–145.CrossRefGoogle Scholar
  42. 42.
    Ebert, S. N., Taylor, D. G., Nguyen, H. L., Kodack, D. P., Beyers, R. J., Xu, Y., et-al. (2007). Non-invasive tracking of cardiac embryonic stem cells in vivo using magnetic resonance imaging techniques. Stem Cells (in press), Aug 9.Google Scholar
  43. 43.
    Rice, H. E., Hsu, E. W., Sheng, H., Evenson, D. A., Freemerman, A. J., Safford, K. M., et al. (2007). Superparamagnetic iron oxide labeling and transplantation of adipose-derived stem cells in middle cerebral artery occlusion-injured mice. American Journal of Roentgenology, 188, 1101–1108.PubMedCrossRefGoogle Scholar
  44. 44.
    Tran, N., Franken, P. R., Maskali, F., Nloga, J., Maureira, P., Poussier, S., et al. (2007). Intramyocardial Implantation of bone marrow-derived stem cells enhances perfusion in chronic myocardial infarction: Dependency on initial perfusion depth and follow-up assessed by gated pinhole SPECT. Journal of Nuclear Medicine, 48, 405–412.PubMedGoogle Scholar
  45. 45.
    Caveliers, V., De Keulenaer, G., Everaert, H., Van Riet, I., Van Camp, G., Verheye, S., et al. (2007). In vivo visualization of 111In labeled CD133+ peripheral blood stem cells after intracoronary administration in patients with chronic ischemic heart disease. Quarterly Journal of Nuclear Medicine and Molecular Imaging, 51, 61–66.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Li Yan
    • 1
    • 2
  • Ying Han
    • 1
  • Yuanlong He
    • 1
  • Huahong Xie
    • 1
  • Jingmei Liu
    • 1
  • Lina Zhao
    • 1
  • Jingbo Wang
    • 1
  • Liuchun Gao
    • 1
  • Daiming Fan
    • 1
  1. 1.Department of GastroenterologyXijing Hospital, Fourth Military Medical UniversityXi’anChina
  2. 2.Department of Gastroenterology401 Hospital of PLAQingdaoChina

Personalised recommendations