Combined use of bFGF/EGF and all-trans-retinoic acid cooperatively promotes neuronal differentiation and neurite outgrowth in neural stem cells

Zhao, Haixia; Zuo, Xuan; Ren, Liyi; Li, Lili; Tai, Haoran; Du, Jing; Xie, Xuemin; Zhang, Xiaoqing; Han, Yuping; Wu, Yongmei; Yang, Chan; Xu, Zhen; Hong, Huarong; Li, Shurong; Su, Bingyin

doi:10.1016/j.neulet.2018.10.002

Cited by 29 publications

(16 citation statements)

References 32 publications

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“…Among other cytokines which exhibit a significant increase, we found EGF, bFGF, AR (amphiregulin, a member of the EGF family), insulin, HGF (hepatocyte growth factor), OPG (Ooteoprotegrin), IGF (insulin-like growth factor), GDNF (glial cell linederived neurotrophic growth factor), etc. As we all know, EGF and bFGF have long been shown to play an important role in neural stem cell maintenance and proliferation [34,35]. The highly increased expression of EGF and bFGF means that these MSC-derived neurospheres can be selfsufficient.…”

mentioning

confidence: 99%

Efficient One-Step Induction of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) Produces MSC-Derived Neurospheres (MSC-NS) with Unique Transcriptional Profile and Enhanced Neurogenic and Angiogenic Secretomes

Peng

et al. 2019

Stem Cells International

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Cell therapy has emerged as a promising strategy for treating neurological diseases such as stroke, spinal cord injury, and various neurodegenerative diseases, but both embryonic neural stem cells and human induced Pluripotent Stem Cell- (iPSC-) derived neural stem cells have major limitations which restrict their broad use in these diseases. We want to find a one-step induction method to transdifferentiate the more easily accessible Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) into neural stem/progenitor cells suitable for cell therapy purposes. In this study, UC-MSCs were induced to form neurospheres under a serum-free suspension culture with Epidermal Growth Factor- (EGF-) and basic Fibroblast Growth Factor- (bFGF-) containing medium within 12 hours. These MSC-derived neurospheres can self-renew to form secondary neurospheres and can be readily induced to become neurons and glial cells. Real-time PCR showed significantly upregulated expression of multiple stemness and neurogenic genes after induction. RNA transcriptional profiling study showed that UC-MSC-derived neurospheres had a unique transcriptional profile of their own, with features of both UC-MSCs and neural stem cells. RayBio human growth factor cytokine array analysis showed significantly upregulated expression levels of multiple neurogenic and angiogenic growth factors, skewing toward a neural stem cell phenotype. Thus, we believe that these UC-MSC-derived neurospheres have amenable features of both MSCs and neural stem/progenitor cells and have great potential in future stem cell transplantation clinical trials targeting neurological disorders.

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mentioning

confidence: 99%

Efficient One-Step Induction of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) Produces MSC-Derived Neurospheres (MSC-NS) with Unique Transcriptional Profile and Enhanced Neurogenic and Angiogenic Secretomes

Peng

et al. 2019

Stem Cells International

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“…Interestingly, the expression of MAP2, NEFL, and Tuj1 was decreased and NEFM did not change. These results suggest that MS-275 and VPA are effective inducers of neuronal differentiation and are, therefore, novel drugs for SH-SY5Y cell differentiation [19,20].…”

Section: Neuronal Marker Genes Highly Expressed With Hdac Inhibitorsmentioning

confidence: 82%

Effects of HDAC inhibitors on neuroblastoma SH-SY5Y cell differentiation into mature neurons via the Wnt signaling pathway

Choi

Hwang

Mahesh

et al. 2022

Preprint

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Histone deacetylase (HDAC) inhibitors affect cell homeostasis, gene expression, and cell cycle progression and promote cell terminal differentiation or apoptosis. However, the effect of HDAC inhibition on SH-SY5Y cells, neuroblastoma cells capable of differentiating into neurons under specific conditions, such as in presence of retinoic acid (RA), is unknown. In this study, we hypothesized that HDAC inhibitors induced the neuronal differentiation of SH-SY5Y cells. To test this hypothesis, we used phase contrast microscopy, immunocytochemistry (ICC), reverse transcriptase PCR (RT-PCR), and western blot analysis. MS-275 and valproic acid (VPA), two HDAC inhibitors, were selected to evaluate neuronal differentiation. It was confirmed that cells treated with MS-275 or VPA differentiated into mature neurons, distinguished by bipolar or multipolar morphologies with elongated branches. In addition, the mRNA expression of neuronal markers (MAP2 and NEFH), the astrocytic marker (GFAP), and the oligodendrocyte marker (CNP) was significantly increased with MS-275 or VPA treatment compared to RA treatment. Interestingly, the mRNA expression of NEFM, another neuronal marker, was only increased in VPA treatment compared to RA treatment. In addition, the protein expression of Tuj1 and NeuN, other neuronal markers, were highly expressed with HDAC inhibitors compared to RA treatment. Furthermore, we confirmed that non-canonical Wnt signaling was upregulated with HDAC inhibitors via MAPK signaling and the Wnt/JNK pathway. Therefore, both MS-275 and VPA promoted the differentiation of SH-SY5Y cells into mature neurons via the Wnt signaling pathway.

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“…Synaptic pruning and synaptic rewiring are the two main steps of synaptic regeneration [ 80 ], which occur within 1 month after stroke [ 26 ]. A series of substances secreted by astrocytes and differentiated NSCs promote neurogenesis, while neurite outgrowth is dependent on VEGF, thrombospondin 1 and 2, and bFGF and EGF released by the transplanted stem cells [ 81 , 82 ]. Further, BDNF released by NSCs differentiated into glial cells promote dendrite growth and myelination [ 83 ], while axonal growth is dependent on the axonal growth cone protein GAP-34 expressed by the transplanted cells [ 30 ].…”

Section: Stem Cell Therapies For Ischemic Strokementioning

confidence: 99%

Stem Cell- and Cell-Based Therapies for Ischemic Stroke

Nistor-Cseppentö

Jurcău

et al. 2022

Bioengineering

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Stroke is the second cause of disability worldwide as it is expected to increase its incidence and prevalence. Despite efforts to increase the number of patients eligible for recanalization therapies, a significant proportion of stroke survivors remain permanently disabled. This outcome boosted the search for efficient neurorestorative methods. Stem cells act through multiple pathways: cell replacement, the secretion of growth factors, promoting endogenous reparative pathways, angiogenesis, and the modulation of neuroinflammation. Although neural stem cells are difficult to obtain, pose a series of ethical issues, and require intracerebral delivery, mesenchymal stem cells are less immunogenic, are easy to obtain, and can be transplanted via intravenous, intra-arterial, or intranasal routes. Extracellular vesicles and exosomes have similar actions and are easier to obtain, also allowing for engineering to deliver specific molecules or RNAs and to promote the desired effects. Appropriate timing, dosing, and delivery protocols must be established, and the possibility of tumorigenesis must be settled. Nonetheless, stem cell- and cell-based therapies for stroke have already entered clinical trials. Although safe, the evidence for efficacy is less impressive so far. Hopefully, the STEP guidelines and the SPAN program will improve the success rate. As such, stem cell- and cell-based therapy for ischemic stroke holds great promise.

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Combined use of bFGF/EGF and all-trans-retinoic acid cooperatively promotes neuronal differentiation and neurite outgrowth in neural stem cells

Cited by 29 publications

References 32 publications

Efficient One-Step Induction of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) Produces MSC-Derived Neurospheres (MSC-NS) with Unique Transcriptional Profile and Enhanced Neurogenic and Angiogenic Secretomes

Efficient One-Step Induction of Human Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSCs) Produces MSC-Derived Neurospheres (MSC-NS) with Unique Transcriptional Profile and Enhanced Neurogenic and Angiogenic Secretomes

Effects of HDAC inhibitors on neuroblastoma SH-SY5Y cell differentiation into mature neurons via the Wnt signaling pathway

Stem Cell- and Cell-Based Therapies for Ischemic Stroke

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