Small molecules re-establish neural cell fate of human fibroblasts via autophagy activation

Rujanapun, Narawadee; Heebkaew, Nudjanad; Promjantuek, Wilasinee; Sotthibundhu, Areechun; Kunhorm, Phongsakorn; Chaicharoenaudomrung, Nipha; Noisa, Parinya

doi:10.1007/s11626-019-00381-0

Cited by 5 publications

(2 citation statements)

References 58 publications

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“…Fetal NSCs can be expanded for a long period in vitro, while adult NSCs have more partial abilities [49,50]. Nevertheless, both cell types have an ineffective differentiation potential into neurons after numerous in vitro routes when they are transplanted into in vivo models [51,52]. Several studies have demonstrated that adult NSCs are located in the spinal cord and usually around the central canal with narrow extension to the ventricular system stretching across the length of the spinal cord [53][54][55][56].…”

Section: Neural Stem Cellsmentioning

confidence: 99%

Elucidating the Pivotal Neuroimmunomodulation of Stem Cells in Spinal Cord Injury Repair

Richard¹,

Sackey

2021

Stem Cells International

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Spinal cord injury (SCI) is a distressing incident with abrupt onset of the motor as well as sensory dysfunction, and most often, the injury occurs as result of high-energy or velocity accidents as well as contact sports and falls in the elderly. The key challenges associated with nerve repair are the lack of self-repair as well as neurotrophic factors and primary and secondary neuronal apoptosis, as well as factors that prevent the regeneration of axons locally. Neurons that survive the initial traumatic damage may be lost due to pathogenic activities like neuroinflammation and apoptosis. Implanted stem cells are capable of differentiating into neural cells that replace injured cells as well as offer local neurotrophic factors that aid neuroprotection, immunomodulation, axonal sprouting, axonal regeneration, and remyelination. At the microenvironment of SCI, stem cells are capable of producing growth factors like brain-derived neurotrophic factor and nerve growth factor which triggers neuronal survival as well as axonal regrowth. Although stem cells have proven to be of therapeutic value in SCI, the major disadvantage of some of the cell types is the risk for tumorigenicity due to the contamination of undifferentiated cells prior to transplantation. Local administration of stem cells via either direct cellular injection into the spinal cord parenchyma or intrathecal administration into the subarachnoid space is currently the best transplantation modality for stem cells during SCI.

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Section: Neural Stem Cellsmentioning

confidence: 99%

Elucidating the Pivotal Neuroimmunomodulation of Stem Cells in Spinal Cord Injury Repair

Richard¹,

Sackey

2021

Stem Cells International

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“…Some researchers have found that fibroblasts can be directly reprogrammed into induced neurons (iNs) by combinations of TFs or TFs combined with small-molecule compounds (SMs). , However, the insertion of ectopic genes often requires viral vectors and integration of retroviral vectors into the reprogrammed genome carries the risk of insertion mutations, residual expression, and activation of transgenes, which may induce host oncogenesis. , Moreover, some challenges such as complexity of use, the need for a large amount of time, and low induction efficiency weaken the application value of this strategy . Researchers have demonstrated that terminally differentiated somatic cells can be reprogrammed into neuronal cells with SMs alone, which may improve the safety and efficacy of cell therapy. − SMs can improve conversion efficiency by inhibiting DNA methyltransferase and histone deacetylase (HDAC) and regulating related signaling pathways. − …”

Section: Introductionmentioning

confidence: 99%

Reprogramming of Rat Fibroblasts into Induced Neurons by Small-Molecule Compounds In Vitro and In Vivo

Wang

et al. 2022

ACS Chem. Neurosci.

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Cell replacement is a promising approach for neurodegenerative disease treatment. Somatic cells such as fibroblasts can be induced to differentiate into neurons by specific transcription factors; however, the potential of viral vectors used for reprogramming to integrate into the genome raises concerns about the potential clinical applications of this approach. Here, we directly reprogrammed rat embryonic skin fibroblasts into induced neurons (iNs) via six small-molecule compounds (SMs) (VPA, CHIR99021, forskolin, Y-27632, Repsox, and P7C3-A20). iNs exhibit typical neuronal morphology, and immunofluorescence showed that more than 96% of the iNs expressed the early neuronal marker class III beta-tubulin (TUJ1) and that more than 91% of iNs expressed the mature neuronal marker neuron-specific enolase (NSE) after 10 days of reprogramming. Quantitative real-time polymerase chain reaction also showed that most iNs expressed the dopaminergic neuron marker tyrosine hydroxylase, the neural marker Nur correlation factor 1, the (γ-aminobutyric acid, GABA) GABAergic neuronal marker GABA, and the cholinergic neuron marker choline acetyltransferase. In addition, we found that cell proliferation decreased during reprogramming and that protein synthesis increased initially and then decreased. SMs were mixed with hydrogels, and the hydrogels were implanted subcutaneously into the backs of rats. After 7 days, the TUJ1 and NSE proteins were expressed in surrounding tissues, indicating that SMs caused reprogramming in vivo. In summary, rat skin fibroblasts can be efficiently reprogrammed into iNs by SMs in vitro and in vivo.

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Combination of Melatonin and Small Molecules Improved Reprogramming Neural Cell Fates via Autophagy Activation

et al. 2021

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Small molecules re-establish neural cell fate of human fibroblasts via autophagy activation

Cited by 5 publications

References 58 publications

Elucidating the Pivotal Neuroimmunomodulation of Stem Cells in Spinal Cord Injury Repair

Elucidating the Pivotal Neuroimmunomodulation of Stem Cells in Spinal Cord Injury Repair

Reprogramming of Rat Fibroblasts into Induced Neurons by Small-Molecule Compounds In Vitro and In Vivo

Combination of Melatonin and Small Molecules Improved Reprogramming Neural Cell Fates via Autophagy Activation

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