ArticleMilitary Medical Research2020
Direct conversion of human fibroblasts into dopaminergic neuron-like cells using small molecules and protein factors.
Article in Military Medical Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Chemical transdifferentiation of somatic cells to neural cells: a systematic review.Einstein (Sao Paulo, Brazil) · 2024Pooled it
- Cell-based regenerative interventions in Parkinson's disease: Overcoming pharmacological limitations.Acta pharmaceutica Sinica. B · 2026Review
- Neurogenic inducers inhibit the proliferation of pancreatic cancer by promoting tumor cell transdifferentiation.Journal of experimental & clinical cancer research : CR · 2025Article
- Neuronal FGF13 Inhibits Mitochondria-Derived Damage Signals to Prevent Neuroinflammation and Neurodegeneration in a Mouse Model of Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Progress in direct reprogramming of dopaminergic cell replacement therapy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Review
- Astragaloside IV Treats Parkinson's Disease by Regulating the Proliferation and Differentiation of NSCs through the SHH-Nurr1 Pathway.Stem cells international · 2024Article
- Next-generation direct reprogramming.Frontiers in cell and developmental biology · 2024Review
- In Vitro Modeling as a Tool for Testing Therapeutics for Spinal Muscular Atrophy and IGHMBP2-Related Disorders.Biology · 2023Article
- Mechanisms of Glucocerebrosidase Dysfunction in Parkinson's Disease.Journal of molecular biology · 2023Review
- Strategic Application of Epigenetic Regulators for Efficient Neuronal Reprogramming of Human Fibroblasts.International journal of stem cells · 2023Article
- Escape from oncogene-induced senescence is controlled by POU2F2 and memorized by chromatin scars.Cell genomics · 2023Article
- Somatic Cell Reprogramming for Nervous System Diseases: Techniques, Mechanisms, Potential Applications, and Challenges.Brain sciences · 2023Review
- Retinal Ganglion Cells in a Dish: Current Strategies and Recommended Best Practices for Effective In Vitro Modeling of Development and Disease.Handbook of experimental pharmacology · 2023Review
- Notch4 participates in mesenchymal stem cell-induced differentiation in 3D-printed matrix and is implicated in eccrine sweat gland morphogenesis.Burns & trauma · 2023Article
- EndogenousNeural regeneration research · 2022Review
- Limitations and challenges of direct cell reprogramming in vitro and in vivo.Histology and histopathology · 2022Review
- Application of Small Molecules in the Central Nervous System Direct Neuronal Reprogramming.Frontiers in bioengineering and biotechnology · 2022Review
- Review
- Repair cell first, then regenerate the tissues and organs.Military Medical Research · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGeneration of neurons is essential in cell replacement therapy for neurodegenerative disorders like Parkinson's disease. Several studies have reported the generation of dopaminergic (DA) neurons from mouse and human fibroblasts by ectopic expression of transcription factors, in which genetic manipulation is associated with potential risks.
methodsThe small molecules and protein factors were selected based on their function to directly induce human fetal lung IMR-90 fibroblasts into DA neuron-like cells. Microscopical, immunocytochemical, and RT-qPCR analyses were used to characterize the morphology, phenotype, and gene expression features of the induced cells. The whole-cell patch-clamp recordings were exploited to measure the electrophysiological properties.
resultsHuman IMR-90 fibroblasts were rapidly converted into DA neuron-like cells after the chemical induction using small molecules and protein factors, with a yield of approximately 95% positive TUJ1-positive cells. The induced DA neuron-like cells were immunopositive for pan-neuronal markers MAP2, NEUN, and Synapsin 1 and DA markers TH, DDC, DAT, and NURR1. The chemical induction process did not involve a neural progenitor/stem cell intermediate stage. The induced neurons could fire single action potentials, which reflected partially the electrophysiological properties of neurons.
conclusionWe developed a chemical cocktail of small molecules and protein factors to convert human fibroblasts into DA neuron-like cells without passing through a neural progenitor/stem cell intermediate stage. The induced DA neuron-like cells from human fibroblasts might provide a cellular source for cell-based therapy of Parkinson's disease in the future.
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