Endovascular transplantation of stem cells to the injured rat CNS.
BACKGROUND
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 transplantation 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.


CONCLUSIONS
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.
Lundberg
Johan
J
Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Karolinska University Hospital, 17176 Stockholm, Sweden.
Le Blanc
Katarina
K
Söderman
Mikael
M
Andersson
Tommy
T
Holmin
Staffan
S
D000328:Adult; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000601:surgery; D001930:Brain Injuries / Q000378:metabolism / Q000601:surgery* / Q000628:therapy*; D002343:Carotid Artery, Internal / Q000378:metabolism / Q000601:surgery*; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality; D006801:Humans; D007150:Immunohistochemistry; D007269:Injections, Intra-Arterial / Q000009:adverse effects / Q000379:methods; D007275:Injections, Intravenous / Q000009:adverse effects; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D019060:Minimally Invasive Surgical Procedures / Q000009:adverse effects / Q000379:methods; D019635:Neurosurgical Procedures / Q000009:adverse effects / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000378:metabolism; D016896:Treatment Outcome