Journal
CYTOTHERAPY
Volume 18, Issue 6, Pages 785-796Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2016.03.296
Keywords
amyotrophic lateral sclerosis; brain; magnetic resonance spectroscopy; outcome; spinal cord; stem cells
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Funding
- Carlos III Institute [FIS EC07/90762]
- Advanced Therapies and Transplant General Direction (Health Ministry, Spain) [TRA-137]
- ISCIII Spanish Cell Therapy Network (Tercel) [RD06/0010/0023]
- Fundacion Diogenes
- Ingenio [MECCONSOLIDER CSD2007-00023]
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Background aims. We aimed to investigate whether magnetic resonance spectroscopy (MRS) metabolite ratios change in the precentral gyrus of patients with amyotrophic lateral sclerosis (ALS) after spinal cord surgical injection of bone marrow mononuclear cells, as well as their relationship with disability and survival. Methods. Stem cells were surgically injected in the spinal cord of 11 spinal-onset amyotrophic lateral sclerosis patients (group 1); 21 matched patients were the control group (group 2), comprising ALS patients with an intrathecal saline infusion. Single-voxel 1.5T MRS was performed in both precentral gyri just after inclusion/baseline (before surgery in group 1) and a year later (7 patients in group 1 and 11 in group 2). The spectroscopy data, time of survival and clinical parameters (ALS Functional Rating Scale, forced vital capacity [FVC], Medical Research Council Score) were longitudinally assessed and correlated in both groups. Results. Only in group 1 was there a significant N-acetyl-aspartate/creatine (NAA/Cr) increase with time in the dominant side (P=0.024). NAA/Cr also correlated with years of survival in the nondominant side (r = 0.808, P = 0.026). Except for FVC, all group 1 clinical parameters at 12 months correlated with baseline NAA/Cr on both sides (P < 0.05); this was not the case in group 2. Discussion. In view of these results, we speculate on a distant beneficial effect of bone marrow stem cells injected at the spinal cord over the upper motor neuron at the precentral gyri in the brain. Spinal cord injection of stem cells shows metabolic improvement in the brain that might be related to longer survival and less disability.
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