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Neuroradiology

, Volume 51, Issue 10, pp 661–667 | Cite as

Endovascular transplantation of stem cells to the injured rat CNS

  • Johan Lundberg
  • Katarina Le Blanc
  • Mikael Söderman
  • Tommy Andersson
  • Staffan Holmin
Interventional Neuroradiology

Abstract

Introduction

Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood–brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment.

Methods

Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells.

Results

Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p < 0.01) and 5 days (p < 0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed.

Conclusion

Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases.

Keywords

Trauma Mesenchymal MAB 1281 Intra-arterial 

Notes

Acknowledgments

Mrs. Britt Meijer is thanked for her excellent technical assistance. This study was supported by the Swedish Research Council (2005-19973-31999-24, K2006-32X-14716-04-1, K2008-64X-20742-01-3, K2008-64P-15457-04-3), the Swedish Cancer Society (07 0132, 07 0529), the Children’s Cancer Foundation (05/077), the Cancer Society in Stockholm, the Tobias Foundation, the Sven and Ebba-Christina Hagbergs Foundation, the Karolinska Institutet, ALF funding from the Stockholm County Council, and the Swedish Society of Medicine.

Conflict of interest statement

We declare that we have no conflict of interest.

References

  1. 1.
    Englund U, Fricker-Gates RA, Lundberg C et al (2002) Transplantation of human neural progenitor cells into the neonatal rat brain: extensive migration and differentiation with long-distance axonal projections. Exp Neurol 173:1–21PubMedCrossRefGoogle Scholar
  2. 2.
    Jeong SW, Chu K, Jung KH et al (2003) Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke 34:2258–2263PubMedCrossRefGoogle Scholar
  3. 3.
    Mahmood A, Lu D, Qu C et al (2006) Long-term recovery after bone marrow stromal cell treatment of traumatic brain injury in rats. J Neurosurg 104:272–277PubMedCrossRefGoogle Scholar
  4. 4.
    Kordower JH, Freeman TB, Snow BJ et al (1995) Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson’s disease. N Engl J Med 332:1118–1124PubMedCrossRefGoogle Scholar
  5. 5.
    Bang OY, Lee JS, Lee PH et al (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57:874–882PubMedCrossRefGoogle Scholar
  6. 6.
    Wennersten A, Meier X, Holmin S et al (2004) Proliferation, migration, and differentiation of human neural stem/progenitor cells after transplantation into a rat model of traumatic brain injury. J Neurosurg 100:88–96PubMedCrossRefGoogle Scholar
  7. 7.
    Chen J, Zhang ZG, Li Y et al (2003) Intravenous administration of human bone marrow stromal cells induces angiogenesis in the ischemic boundary zone after stroke in rats. Circ Res 92:692–699PubMedCrossRefGoogle Scholar
  8. 8.
    Shen LH, Li Y, Chen J et al (2006) Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 137:393–399PubMedCrossRefGoogle Scholar
  9. 9.
    Liu W, Jiang X, Fu X et al (2008) Bone marrow stromal cells can be delivered to the site of traumatic brain injury via intrathecal transplantation in rabbits. Neurosci Lett 434:60–164Google Scholar
  10. 10.
    Jin K, Sun Y, Xie L et al (2005) Comparison of ischemia-directed migration of neural precursor cells after intrastriatal, intraventricular, or intravenous transplantation in the rat. Neurobiol Dis 18:366–374PubMedCrossRefGoogle Scholar
  11. 11.
    Guzman R, De Los Angeles A, Cheshier S et al (2008) Intracarotid injection of fluorescence activated cell-sorted CD49d-positive neural stem cells improves targeted cell delivery and behavior after stroke in a mouse stroke model. Stroke 39:1300–1306PubMedCrossRefGoogle Scholar
  12. 12.
    Li Y, Chen J, Wang L et al (2001) Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 56:1666–1672PubMedGoogle Scholar
  13. 13.
    Feeney DM, Boyeson MG, Linn RT et al (1981) Responses to cortical injury: I. Methodology and local effects of contusions in the rat. Brain Res 211:67–77PubMedCrossRefGoogle Scholar
  14. 14.
    Grinnemo KH, Mansson-Broberg A, Leblanc K et al (2006) Human mesenchymal stem cells do not differentiate into cardiomyocytes in a cardiac ischemic xenomodel. Ann Med 38:144–153PubMedCrossRefGoogle Scholar
  15. 15.
    Holmin S, Schalling M, Hojeberg B et al (1997) Delayed cytokine expression in rat brain following experimental contusion. J Neurosurg 86:493–504PubMedCrossRefGoogle Scholar
  16. 16.
    von Gertten C, Flores Morales A, Holmin S et al (2005) Genomic responses in rat cerebral cortex after traumatic brain injury. BMC Neurosci 6:69CrossRefGoogle Scholar
  17. 17.
    Bederson JB, Pitts LH, Tsuji M et al (1986) Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 17:472–476PubMedGoogle Scholar
  18. 18.
    John D, Bancroft AS (1996) Theory and practice of histological techniques, 4th edn. Churcill Livingstone, LondonGoogle Scholar
  19. 19.
    Schachinger V, Erbs S, Elsasser A et al (2006) Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J 27:2775–2783PubMedCrossRefGoogle Scholar
  20. 20.
    Seyfried D, Ding J, Han Y et al (2006) Effects of intravenous administration of human bone marrow stromal cells after intracerebral hemorrhage in rats. J Neurosurg 104:313–318PubMedCrossRefGoogle Scholar
  21. 21.
    Politi LS (2007) MR-based imaging of neural stem cells. Neuroradiology 49:523–534PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Johan Lundberg
    • 1
  • Katarina Le Blanc
    • 2
  • Mikael Söderman
    • 1
  • Tommy Andersson
    • 1
  • Staffan Holmin
    • 1
  1. 1.Department of Clinical Neuroscience, Karolinska Institutet, Department of NeuroradiologyKarolinska University HospitalStockholmSweden
  2. 2.Department of Stem Cell Research, Karolinska Institutet, Department of Clinical ImmunologyKarolinska University HospitalStockholmSweden

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