Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

Abstract

Aims:Mutations in DNA/RNA-binding factor (fused-in-sarcoma) FUS and superoxide dismutase-1 (SOD-1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD-1-G93A (SOD-1) and new FUS[1-359]-transgenic (FUS-tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti-inflammatory treatments were investigated using these mutants. Methods: FUS-tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti-inflammatory drug a selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro-Cells (a preparation of 1.39 × 10 6 mesenchymal and hemopoietic human stem cells, containing 5 × 10 5 of CD34 + cells), which showed antiinflammatory properties. SOD-1 mice received i.c.v.-administration of Neuro-Cells or vehicle.Results: All FUS-tg-treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS-tg-vehicle-treated mice. Neuro-Celltreated mutants had reduced muscle atrophy and lumbar motor neuron degeneration.This group but not celecoxib-FUS-tg-treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium-binding adapter molecule-1 (Iba-1), and glycogen-synthase-kinase-3ß (GSK-3ß). The Neuro-Cells-treated-SOD-1 mice showed better motor functions than vehicle-treated-SOD-1 group. Conclusion:The neuropathology in FUS-tg mice is sensitive to standard ALS treatments and Neuro-Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation. | 505MUNTER ET al.

Treatment of rats with spinal cord injury using human bone marrow-derived stromal cells prepared by negative selection

“…3) Thus, the time of intervention is another crucial parameter when considering stem cell therapy of SCI. By far the most animal experiments have been carried out in the acute phase, and with bmSC this seems to be justified because their main benefit is expected to be neuroprotection by modulating the immediate inflammatory response [3,13,45]. Our histological evaluation indicates that the acute intervention, while not reducing gross tissue damage (Fig.…”

“…It is therefore an objective to modify the tissue response such that implanted cells remain functional. Since the bmSC themselves modulate the innate immune system [26,45,47], we suggest that a combination of pharmacological/cellbased therapies should complement the signals released from the bmSC by activating different molecular targets.…”

Dibenzoylthiamine Has Powerful Antioxidant and Anti-Inflammatory Properties in Cultured Cells and in Mouse Models of Stress and Neurodegeneration

“…At the age of 9 weeks, groups of female FUS-tg (Thy-1.FUS 1–359) mice and wild type littermates were treated as described in the Supplemental Materials and Methods File S2 . Briefly, administration of DBT (50 mg/kg/day) or thiamine (50 or 200 mg/kg/day), or riluzole (2-amino-6-trifluoromethoxy-benzothiazole, 8 mg/kg/day) was started by a replacement of drinking water with treatment solutions as described elsewhere [ 12 , 15 , 35 ]. Selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) was administered via food pellets as described elsewhere [ 35 , 36 ].…”

“…Briefly, administration of DBT (50 mg/kg/day) or thiamine (50 or 200 mg/kg/day), or riluzole (2-amino-6-trifluoromethoxy-benzothiazole, 8 mg/kg/day) was started by a replacement of drinking water with treatment solutions as described elsewhere [ 12 , 15 , 35 ]. Selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) was administered via food pellets as described elsewhere [ 35 , 36 ]. After 5 weeks of dosing and monitoring of the body weight and liquid intake of the animals, their latency to fall was scored in the wire test on weeks 5 and 6 as described elsewhere [ 35 , 37 ].…”

Stem cell therapy and FUS[1‐359]‐transgenic mice: A recent study highlighting a promising ALS model and a promising therapy

“…The article of de Munter and co‐authors “ Neuro‐Cell therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice ” has shown that their novel approach has beneficial effect in the G93A SOD‐1 mutant and the more recently described FUS[1‐359] ‐transgenic mouse, which confers a number of advantages over “golden standard” SOD‐1‐G93A line. The study employs a new stem cell preparation known as “Neuro‐Cells” (Neuroplast, Netherlands), which are argued to have novel antiinflammatory actions, such as the suppression of microglial activation, as part of their “stem cell” activity.…”