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Behav Brain Res. 2014 Feb 1;259:50-9. doi: 10.1016/j.bbr.2013.10.030. Epub 2013 Oct 29.

Human bone marrow mesenchymal stem/stromal cells produce efficient localization in the brain and enhanced angiogenesis after intra-arterial delivery in rats with cerebral ischemia, but this is not translated to behavioral recovery.

Author information

1
Institute of Clinical Medicine-Neurology, University of Eastern Finland, Yliopistonranta 1 C, Kuopio, Finland.
2
Finnish Red Cross Blood Service, Advanced Therapies and Product Development, Helsinki, Finland.
3
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
4
Institute of Clinical Medicine-Neurology, University of Eastern Finland, Yliopistonranta 1 C, Kuopio, Finland. Electronic address: jukka.jolkkonen@uef.fi.

Abstract

Intravascular cell therapy is a promising approach for the treatment of stroke. However, high accumulation of cells to lungs and other filtering organs is a major concern after intravenous (i.v.) cell transplantation. This can be circumvented by intra-arterial (i.a.) cell infusion, which improves homing of cells to the injured brain. We studied the effect of i.a. delivery of human bone marrow-derived mesenchymal cells (BMMSCs) on behavioral and histological outcome in rats after middle cerebral artery occlusion (MCAO). Sixty male Wistar rats were subjected to transient MCAO (60 min) or sham-operation. BMMSCs (1×10(6)) were infused into the external carotid artery on postoperative day 2 or 7. Histology performed after a 42-day follow-up did not detect any human cells (MAB1281) in the ischemic brain. Endothelial cell staining with RECA-1 revealed a significant increase in the number of blood vessels in the perilesional cortex in MCAO rats treated with cells on postoperative day 7. Behavioral recovery as assessed in three tests, sticky label, cylinder and Montoya's staircase, was not improved by human BMMSCs during the follow-up. In conclusion, human BMMSCs did not improve functional recovery in MCAO rats despite effective initial homing to the ischemic hemisphere and enhanced angiogenesis, when strict behavioral tests not affected by repeated testing and compensation were utilized.

KEYWORDS:

Angiogenesis; Behavioral recovery; Cell therapy; Cerebral ischemia; Human bone marrow derived mesenchymal cells; Intravascular delivery

PMID:
24177208
DOI:
10.1016/j.bbr.2013.10.030
[Indexed for MEDLINE]

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