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Published in: Neuroradiology 10/2009

01-10-2009 | Interventional Neuroradiology

Endovascular transplantation of stem cells to the injured rat CNS

Authors: Johan Lundberg, Katarina Le Blanc, Mikael Söderman, Tommy Andersson, Staffan Holmin

Published in: Neuroradiology | Issue 10/2009

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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.
Literature
1.
go back to reference 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 173:1–21PubMedCrossRef 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 173:1–21PubMedCrossRef
2.
go back to reference Jeong SW, Chu K, Jung KH et al (2003) Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke 34:2258–2263PubMedCrossRef Jeong SW, Chu K, Jung KH et al (2003) Human neural stem cell transplantation promotes functional recovery in rats with experimental intracerebral hemorrhage. Stroke 34:2258–2263PubMedCrossRef
3.
go back to reference 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 104:272–277PubMedCrossRef 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 104:272–277PubMedCrossRef
4.
go back to reference 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 332:1118–1124PubMedCrossRef 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 332:1118–1124PubMedCrossRef
5.
go back to reference Bang OY, Lee JS, Lee PH et al (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57:874–882PubMedCrossRef Bang OY, Lee JS, Lee PH et al (2005) Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57:874–882PubMedCrossRef
6.
go back to reference 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 100:88–96PubMedCrossRef 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 100:88–96PubMedCrossRef
7.
go back to reference 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 92:692–699PubMedCrossRef 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 92:692–699PubMedCrossRef
8.
go back to reference Shen LH, Li Y, Chen J et al (2006) Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 137:393–399PubMedCrossRef Shen LH, Li Y, Chen J et al (2006) Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 137:393–399PubMedCrossRef
9.
go back to reference 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 434:60–164 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 434:60–164
10.
go back to reference 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 18:366–374PubMedCrossRef 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 18:366–374PubMedCrossRef
11.
go back to reference 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 39:1300–1306PubMedCrossRef 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 39:1300–1306PubMedCrossRef
12.
go back to reference Li Y, Chen J, Wang L et al (2001) Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 56:1666–1672PubMed Li Y, Chen J, Wang L et al (2001) Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 56:1666–1672PubMed
13.
go back to reference 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 211:67–77PubMedCrossRef 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 211:67–77PubMedCrossRef
14.
go back to reference 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 38:144–153PubMedCrossRef 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 38:144–153PubMedCrossRef
15.
go back to reference Holmin S, Schalling M, Hojeberg B et al (1997) Delayed cytokine expression in rat brain following experimental contusion. J Neurosurg 86:493–504PubMedCrossRef Holmin S, Schalling M, Hojeberg B et al (1997) Delayed cytokine expression in rat brain following experimental contusion. J Neurosurg 86:493–504PubMedCrossRef
16.
go back to reference von Gertten C, Flores Morales A, Holmin S et al (2005) Genomic responses in rat cerebral cortex after traumatic brain injury. BMC Neurosci 6:69CrossRef von Gertten C, Flores Morales A, Holmin S et al (2005) Genomic responses in rat cerebral cortex after traumatic brain injury. BMC Neurosci 6:69CrossRef
17.
go back to reference 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 17:472–476PubMed 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 17:472–476PubMed
18.
go back to reference John D, Bancroft AS (1996) Theory and practice of histological techniques, 4th edn. Churcill Livingstone, London John D, Bancroft AS (1996) Theory and practice of histological techniques, 4th edn. Churcill Livingstone, London
19.
go back to reference 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 27:2775–2783PubMedCrossRef 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 27:2775–2783PubMedCrossRef
20.
go back to reference 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 104:313–318PubMedCrossRef 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 104:313–318PubMedCrossRef
Metadata
Title
Endovascular transplantation of stem cells to the injured rat CNS
Authors
Johan Lundberg
Katarina Le Blanc
Mikael Söderman
Tommy Andersson
Staffan Holmin
Publication date
01-10-2009
Publisher
Springer-Verlag
Published in
Neuroradiology / Issue 10/2009
Print ISSN: 0028-3940
Electronic ISSN: 1432-1920
DOI
https://doi.org/10.1007/s00234-009-0551-6

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