Neurogenic differentiation of human adipose-derived stem cells: Relevance of different signaling molecules, transcription factors, and key marker genes

Cardozo, Alejandra; Gómez, Daniel E.; Argibay, Pablo

doi:10.1016/j.gene.2012.09.038

Cited by 50 publications

(37 citation statements)

References 75 publications

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“…Immunohistochemical analyses have revealed high beta-tubulin isotype III expression levels in differentiating ADSCs after 14 days of neurogenic induction 6 , which is in accordance with our immunostaining results. MAP-2 is expressed at the later time points by the mature neurons 1 and the high expression levels were maintained at day 14 only when cells were stimulated with both current and copper confirmed by immunostaining and real-time PCR.…”

Section: Discussionsupporting

confidence: 91%

“…We investigated this effect in more detail and exposed the cells to two different currents and amounts of external copper. We studied the marker expression up to 14 days as it is commonly used latest time point in other studies 6,34 and allows enough time to detect the neuronal changes that can often be seen as early as 1-3 hours after induction 34 .…”

Section: Discussionmentioning

confidence: 99%

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The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells

Jaatinen

Salemi

Miettinen³

et al. 2014

Ann Biomed Eng

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Damage to the nervous system can be caused by several types of insults, and it always has a great effect on the life of an individual. Due to the limited availability of neural transplants, alternative approaches for neural regeneration must be developed. Stem cells have a great potential to support neuronal regeneration. Human adipose-derived stem cells (hADSCs) have gained increasing interest in the fields of regenerative medicine due to their multilineage potential and easy harvest compared to other stem cells. In this study, we present a growth factor-free method for the differentiation of hADSCs toward neuron-like cells. We investigated the effect of electric current and copper on neuronal differentiation. We analyzed the morphological changes, the mRNA and protein expression levels in the stimulated cells and showed that the combination of current and copper induces stem cell differentiation toward the neuronal lineage with elongation of the cells and the upregulation of neuron-specific genes and proteins. The induction of the neuronal differentiation of hADSCs by electric field and copper may offer a novel approach for stem cell differentiation and may be a useful tool for safe stem cell-based therapeutic applications. Abstract and key termsDamage to the nervous system can be caused by several types of insults, and it always has a great effect on the life of an individual. Due to the limited availability of neural transplants, alternative approaches for neural regeneration must be developed. Stem cells have a great potential to support neuronal regeneration.Human adipose-derived stem cells (hADSCs) have gained increasing interest in the fields of regenerative medicine due to their multilineage potential and easy harvest compared to other stem cells. In this study, we present a growth factor-free method for the differentiation of hADSCs toward neuron-like cells. We investigated the effect of electric current and copper on neuronal differentiation. We analyzed the morphological changes, the mRNA and protein expression levels in the stimulated cells and showed that the combination of current and copper induces stem cell differentiation toward the neuronal lineage with elongation of the cells and the upregulation of neuron-specific genes and proteins. The induction of the neuronal differentiation of hADSCs by electric field and copper may offer a novel approach for stem cell differentiation and may be a useful tool for safe stem cell-based therapeutic applications.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells

Jaatinen

Salemi

Miettinen³

et al. 2014

Ann Biomed Eng

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“…In addition to the combined effect, BDNF and NGF exerted a competitive effect on neuronal precursors in the combination group. NeuroD drives neural differentiation of precursor cells (30). In the results of the present study, NeuroD expression levels were increased the most in the combination group, and were enhanced in immature and mature neurons following the beginning of differentiation towards a neural phenotype.…”

Section: Discussionmentioning

confidence: 99%

Combined effect of nerve growth factor and brain-derived neurotrophic factor on neuronal differentiation of neural stem cells and the potential molecular mechanisms

Liu

Xuan

Chen

et al. 2014

Molecular Medicine Reports

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Neural stem cells (NSCs) are important pluripotent stem cells, which have potential applications in cell replacement therapy. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) have been demonstrated to exert a marked impact on the proliferation and differentiation of NSCs. The effects of NGF, BDNF, and BDNF combined with NGF on NSC neuronal differentiation and the possible mechanisms for these effects were investigated in this study. An adherent monolayer culture was employed to obtain highly homogeneous NSCs. The cells were divided into four groups: Control, NGF, BDNF and combination (BDNF + NGF) groups. Neuron differentiation was examined using immunocytochemistry and phospho-extracellular signal-regulated kinase (p-ERK) levels were analyzed using western blotting. Reverse transcription polymerase chain reaction was used to measure the mRNA expression levels of the HES1, HES5, MASH1, NGN1 and NeuroD transcription factors at different time intervals following neurotrophin-induced differentiation. NGF and BDNF were observed to induce NSC neuronal differentiation, and β-tubulin III-positive cells and p-ERK expression levels were highest in the NGF + BDNF combination group at all time points. The proportion of β-tubulin III-positive neurons in each group was associated with the expression levels of MASH1, NGN1 and NeuroD in the group. In conclusion, BDNF combined with NGF significantly improved NSC neuronal differentiation, which may provide support for the practical application of NSCs in neurodegenerative diseases.

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“…Stem cells, derived from various tissue sources and capable of differentiating into many cell types, provide an attractive option for cellular therapies in neurological diseases. Stem cells in the body differentiate into several cell types based on various environmental cues, and studies have shown that neural-like and glial-like cells can be successfully generated from multiple (human and animal) stem cells (Kim & de Vellis, 2009), including induced pluripotent stem cells (iPSCs) (Kuo & Chang, 2012; Kuo & Wang, 2012), embryonic stem cells (ESCs) (Ostrakhovitch et al, 2012), mesenchymal stem/stromal cells (MSCs) (Cardozo et al, 2012), and neural stem cells (Ribeiro et al, 2012; Ostrakhovitch et al, 2012). MSCs, the most widely studied stem cell type, have undergone several protocols for generating neural-like cells.…”

Section: Introductionmentioning

confidence: 99%

Neurogenesis of Neural Crest‐Derived Periodontal Ligament Stem Cells by EGF and bFGF

Fortino

Chen

Pelaez

et al. 2013

Journal Cellular Physiology

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Neuroregenerative medicine is an ever-growing field in which regeneration of lost cells/tissues due to a neurodegenerative disease is the ultimate goal. With the scarcity of available replacement alternatives, stem cells provide an attractive source for regenerating neural tissue. While many stem cell sources exist, including: mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), the limited cellular potency, technical difficulties, and ethical considerations associated with these make finding alternate sources a desirable goal. Periodontal ligament stem cells (PDLSCs) derived from the neural crest were induced into neural-like cells using a combination of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Morphological changes were evident in our treated group, seen under both light microscopy and scanning electron microscopy (SEM). A statistically significant increase in the expression of neuron-specific β-tubulin III and the neural stem/progenitor cell marker nestin, along with positive immunohistochemical staining for glial fibrillary acidic protein (GFAP), demonstrated the success of our treatment in inducing both neuronal and glial phenotypes. Positive staining for synaptophysin demonstrated neural connections and electrophysiological recordings indicated that when subjected to whole cell patch clamping, our treated cells displayed inward currents conducted through voltage-gated sodium (Na+) channels. Taken together, our results indicate the success of our treatment in inducing PDLSCs to neural-like cells. The ease of sourcing and expansion, their embryologic neural crest origin, and the lack of ethical implications in their use make PDLSCs an attractive source for use in neuroregenerative medicine.

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Neurogenic differentiation of human adipose-derived stem cells: Relevance of different signaling molecules, transcription factors, and key marker genes

Cited by 50 publications

References 75 publications

The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells

The Combination of Electric Current and Copper Promotes Neuronal Differentiation of Adipose-Derived Stem Cells

Combined effect of nerve growth factor and brain-derived neurotrophic factor on neuronal differentiation of neural stem cells and the potential molecular mechanisms

Neurogenesis of Neural Crest‐Derived Periodontal Ligament Stem Cells by EGF and bFGF

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