Neurobiology of Disease & Regeneration | Motor Systems | Cerebrovascular Disease | Hematopoietic Stem Cells
Benefit of intravenous injection of clinical grade mesenchymal stem cells after experimental stroke
C Feuerstein, O Detante*, B Naegele, EL Barbier, A Moisan, N Coquery, MJ Richard, E Grillon, F de Fraipont, M Hommel, C Remy
*Corresponding author: O Detante
Grenoble Institut Neurosciences, INSERM U 836, Grenoble, France
Unité Neuro-Vasculaire, Neurologie, Centre Hospitalier Universitaire, Grenoble, France
F1000Posters 2010, 1: 681 (poster) [ENGLISH]
Neuroscience 2010, 13 - 17 Nov 2010, 57.13
Society for Neuroscience
Stroke is the leading cause of disability in adults. Stem cell graft leading to functional recovery after stroke is a promising therapy. However, despite pilot clinical trials showing a clinical improvement, there is limited data available regarding the safety and efficacy of stem cell grafts. Human bone marrow mesenchymal stem cells (hMSC) offer the advantage of not originating from a tumoral or modified source, and benefits have been observed when hMSC is administrated during the acute phase after an experimental stroke.
The purpose of this preclinical study was to assess the functional effects of intravenous (IV) injection of clinical grade hMSC, at the subacute phase in a rat model of stroke.
Rats (n=25) were trained on the Adhesive Removal Test (ART), Neurological Severity Score (NSS), and a spatial memory test (delayed match to sample) on an 8-arm radial maze (RAM). They underwent a 90 minute transient middle cerebral artery occlusion and were allocated into two groups: 1) the treated group (n=13) received an IV injection of 3.106 hMSC one week after the focal cerebral ischemia; 2) the placebo group (n=12) received an IV injection of the cell suspension medium (PBS-glutamine). To identify the cells, hMSC were labelled prior to injection with Iron Fluorophore Particles (IFP) providing a fluorescent label for microscopy and an iron label for MRI. Flow cytometry was performed to assess label efficiency and cell viability. Follow-up (7 weeks) included the behavioral tests and in vivo MRI to follow the lesion size and hMSC migration. Immunohistology was used to identify cells from hMSC.
No adverse effect was observed. Greater sensorimotor and cognitive recoveries were observed in the treated group compared to controls (repeated measures ANOVA for NSS: p=0.007; t-test for RAM post-delay time at 6 weeks: 180.4 ± 27.1 s vs 266.9 ± 17.9 s, p = 0.019). No significant effect was observed on lesion volume. Labeled hMSC could not be distinguished from micro-bleeds during the MRI follow-up. Histology data showed that hMSC could survive in the ischemic lesion for 7 weeks, and that a very few hMSC differentiated into neurons, endothelial or astrocytes.
IV injection of hMSC, one week after experimental stroke, may provide sensorimotor and cognitive benefits. Clinical trials using this approach are warranted.
No relevant conflicts of interest declared.
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