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Mouse spinal cords transplanted with human iPS cell-derived neural cells with and without chemogenetic stimulations on 14-days and 42-days after spinal cord injury.

ABSTRACT: hM3Dq-expressing human iPS cell-derived neural cells were transplanted in the injured mouse spinal cord. Thereafter, transplanted cells were selectively stimulated daily by intraperitoneal injection of CNO. The spinal cord 14-days and 42-days after the injury were eviscerated for analyses.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE173244 | GEO | 2021/11/23

REPOSITORIES: GEO

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Project description:SMARD1 is an infantile autosomal recessive motor neuron (MN) disease, caused by mutations in the Immunoglobulin mu binding protein 2 (IGHMBP2). We investigated the potential of a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase activity (ALDH) to modify disease progression of nmd mice, an animal model of SMARD1. ALDHhiSSClo stem cells are self-renewing and multipotent and when intratechally transplanted in nmd mice generate motor neurons properly localized in the spinal cord ventral horns. Transplanted nmd animals presented delayed disease progression, sparing of motor neurons and ventral root axons and increased life-span. To further investigate the molecular events responsible for these differences, microarray and Real time RT-PCR analysis of wild-type, mutated and transplanted nmd spinal cord were undertaken. We demonstrated a down-regulation of genes involved in excitatory amino acid toxicity and oxidative stress handling, as well as an up-regulation of genes related to the chromatin organization in nmd compared to wild-type mice, suggesting that they may play a role in SMARD1 pathogenesis. Spinal cord of nmd transplanted mice expressed high transcript levels for genes related to neurogenesis such as Doublecortin (DCX), LIS1 and drebrin. The presence of DCX-expressing cells in adult nmd spinal cord suggests that both exogenous and endogenous neurogenesis may contribute to the observed nmd phenotype amelioration. Experiment Overall Design: We intratechally transplanted a spinal cord neural stem cell population isolated on the basis of aldehyde dehydrogenase activity (ALDH) in nmd mice, an animal model of SMARD1. Experiment Overall Design: We analyzed the lumbar spinal cord tract of transplanted nmd mice (n=3), untransplanted nmd mice (n=3) and wild-type mice (n=3) (all mice are of male gender). The latter groups underwent surgical procedure with vehicle. The surgical procedure and cell transplantation were done at P1 and the animals were sacrificed at 6 weeks of age.

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Mouse spinal cords transplanted with human iPS cell-derived neural cells with and without chemogenetic stimulations on 14-days and 42-days after spinal cord injury.

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