ArticleFrontiers in neuroscience2019
Valproic Acid Enhances Reprogramming Efficiency and Neuronal Differentiation on Small Molecules Staged-Induction Neural Stem Cells: Suggested Role of mTOR Signaling.
Article in Frontiers in neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Chemical transdifferentiation of somatic cells to neural cells: a systematic review.Einstein (Sao Paulo, Brazil) · 2024Pooled it
- Therapeutic potential of astrocyte transdifferentiated neurons.Neural regeneration research · 2026Article
- Activation of canonical Wnt signaling is required for efficient direct reprogramming into human hepatic progenitor cells.Stem cell reports · 2025Article
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
- Epigenetic regulation of reprogramming and pluripotency: insights from histone modifications and their implications for cancer stem cell therapies.Frontiers in cell and developmental biology · 2025Review
- Possible Strategies to Reduce the Tumorigenic Risk of Reprogrammed Normal and Cancer Cells.International journal of molecular sciences · 2024Review
- Chemical approaches targeting the hurdles of hepatocyte transplantation: mechanisms, applications, and advances.Frontiers in cell and developmental biology · 2024Review
- Small Molecules Temporarily Induce Neuronal Features in Adult Canine Dermal Fibroblasts.International journal of molecular sciences · 2023Article
- Plumping up a Cushion of Human Biowaste in Regenerative Medicine: Novel Insights into a State-of-the-Art Reserve Arsenal.Stem cell reviews and reports · 2022Review
- Combined cell grafting and VPA administration facilitates neural repair through axonal regeneration and synaptogenesis in traumatic brain injury.Acta biochimica et biophysica Sinica · 2022Article
- Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.Cells · 2022Article
- Application of Small Molecules in the Central Nervous System Direct Neuronal Reprogramming.Frontiers in bioengineering and biotechnology · 2022Review
- Valproic acid promotes the in vitro differentiation of human pluripotent stem cells into spermatogonial stem cell-like cells.Stem cell research & therapy · 2021Article
- Valproic acid stimulates myogenesis in pluripotent stem cell-derived mesodermal progenitors in a NOTCH-dependent manner.Cell death & disease · 2021Article
- Urine-derived induced pluripotent/neural stem cells for modeling neurological diseases.Cell & bioscience · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inducing somatic cells into neural stem cells (iNSCs) in specific ways provides a new cell therapy in a variety of neurological diseases. In the past, iNSCs were generated by transcription factors which increased the risk of mutagenesis, tumor formations, and immune reactions by viral transduction vectors. Therefore, in this study, different small molecules were used to induce mouse embryonic fibroblasts (MEFs) into iNSCs in different reprogramming stages, which showed high reprogramming efficiency without altering the genome. We demonstrated that the small molecules staged-induction neural stem cells (SMSINS) have the characteristics of neural stem cells (NSCs) in morphology, gene expression, self-renewal and differentiation potential. Furthermore, valproic acid (VPA), one of small molecules, was showed to enhance neural induction with highest efficiency compared with six other small molecules, which were also investigated in the present study. Moreover, our results suggested that activating the mammalian target of rapamycin (mTOR) signaling enhanced the induction efficiency and neuronal differentiation. Collectively, our findings indicated that using this induction program allowed us to obtain safe and efficient iNSCs which were free of genetic manipulation. The VPA-mediated mTOR signaling pathway may enhance reprogramming efficiency and neuronal differentiation. So we suggested that this program could be a new method of obtaining iNSCs for the treatment of neurological diseases by cell replacement therapy in the future.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.