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Targeting 17β-estradiol biosynthesis in neural stem cells improves stroke outcome.

Front Cell Neurosci

July 2022

Strathclyde Institute of Pharmacy and Biological Sciences, University of Strathclyde, Glasgow, United Kingdom.

Dax-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital region on X-chromosome gene 1) blocks 17β-estradiol biosynthesis and its knockdown would be expected to increase 17β-estradiol production. We hypothesized that knockdown of Dax-1 in a conditionally immortalized neural stem cell (NSC) line, MHP36, is a useful approach to increase 17β-estradiol production. Short hairpin (sh) RNA targeted to in NSCs, namely MHP36-Dax1KD cells, resulted in the degradation of RNA and attenuation of Dax-1 protein expression.

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Cell therapy has enormous potential to restore neurological function after stroke. The present study investigated effects of conditionally immortalised neural stem cells (ciNSCs), the Maudsley hippocampal murine neural stem cell line clone 36 (MHP36), on sensorimotor and histological outcome in mice subjected to transient middle cerebral artery occlusion (MCAO). Adult male C57BL/6 mice underwent MCAO by intraluminal thread or sham surgery and MHP36 cells or vehicle were implanted into ipsilateral cortex and caudate 2 days later.

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Recent studies have shown that many kinds of stem cells are beneficial for patients suffering with neurodegenerative diseases. We investigated the effects of neural stem cell (NSC), Maudsley hippocampal clone 36 (MHP36) in the Niemann-Pick disease type C (NP-C) model mice. Herein, we demonstrate that MHP36 transplantation improves the neuropathological features without acute immune response and promotes neuronal networks with functional synaptic transmission.

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Positional specification in a neural stem cell line involves modulation of Musashi1 expression.

Stem Cells Dev

April 2010

Centre for the Cellular Basis of Behaviour, King's College London, Institute of Psychiatry, Denmark Hill, London, United Kingdom.

In this study, we have used an in vitro co-culture system to investigate the competency of a conditionally immortalized multipotential neural progenitor cell line (MHP36) to adopt "dorsal" or "striatal" telencephalic fates. We report that MHP36 cells, unlike primary fetal neural progenitors cells, do not express either dorsal or ventral telencephalic positional specification genes; at both the mRNA and protein levels, but that they quickly turn on expression of the appropriate set of proteins when cultured in either a dorsal (cortical) or a ventral (striatal) environment. This control has 2 components: transcriptional activation of positional specification genes, and translational control whereby only the appropriate set of mRNAs appears as immunoreactive protein.

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Non-invasive identification of transplanted neural stem cells in vivo by pre-labelling with contrast agents may play an important role in the translation of cell therapy to the clinic. Understanding the impact of these labels on the cells' ability to repair is therefore vital. In rats with middle cerebral artery occlusion (MCAo), a model of stroke, the transhemispheric migration of MHP36 cells labelled with the bimodal contrast agent GRID was detected on magnetic resonance images (MRI) up to 4 weeks following transplantation.

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