Differentiation of adult rat mesenchymal stem cells to GABAergic, dopaminergic and cholinergic neurons

Borkowska, Paulina; Fila-Daniłow, Anna; Paul-Samojedny, Monika; Kowalczyk, Małgorzata; Hart, Justyna; Ryszawy, Jakub; Kowalski, Jan

doi:10.1016/j.pharep.2014.08.022

Cited by 21 publications

(15 citation statements)

References 25 publications

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“…Several studies have showed differentiation of BMSCs into GABAergic neuron-like cells to facilitate the use of an autologous source of donor cells for grafting in neurological disorders. Some studies have used beta-mercaptoethanol and retinoic acid (RA) as pre-inducers followed by potassium chloride [ 34 ], and others have employed differentiation cocktails comprising a hippocampal astrocyte and glioblastoma conditioned medium [ 7 ] or conditioned medium including Bt2cAMP and acid ATRA [ 11 ]. Moreover, our previous study demonstrated that overexpression of Mash1 can enhance the differentiation of BMSCs into functional GABAergic neuron-like cells [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…Despite these exciting results, the clinical application of GABAergic precursor cell therapy is hampered by both difficulties in obtaining a sufficient amount of donor cells and ethical issues associated with the use of GABAergic precursor cells from fetal brains. From these perspectives, mesenchymal stem cells (MSCs) and induced pluripotent stem cells (iPSC) appear ideal as a starting material for obtaining large numbers of GABAergic precursor cells [ 7 - 9 ].…”

mentioning

confidence: 99%

“…Nonetheless, bone marrow-derived mesenchymal stem cells (BMSCs) have received significant attention due to their amenability for expansion in culture and minimal immunogenicity [ 13 - 15 ]. These cells also have the capability to differentiate into GABAergic neuron-like cells when genetically engineered or treated with a cocktail conditioned medium [ 7 , 10 , 11 ]. Furthermore, previous studies have shown that GABAergic neuron-like cells derived from BMSCs express GABA and GABA A receptors following transplantation into the brain in a cerebral infarct model [ 16 , 17 ].…”

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confidence: 99%

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Mash1-dependent Notch Signaling Pathway Regulates GABAergic Neuron-Like Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells

Long¹,

Luo²,

Wang³

et al. 2017

Aging and disease

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GABAergic neuronal cell grafting has promise for treating a multitude of neurological disorders including epilepsy, age-related memory dysfunction, Alzheimer’s disease and schizophrenia. However, identification of an unlimited source of GABAergic cells is critical for advancing such therapies. Our previous study implied that reprogramming of bone marrow-derived mesenchymal stem cells (BMSCs) through overexpression of the Achaete-scute homolog 1 (Ascl1, also called Mash1) could generate GABAergic neuron-like cells. Here, we investigated mechanisms underlying the conversion of BMSCs into GABAergic cells. We inhibited γ-secretase (an enzyme that activates Notch signaling) with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or manipulated the expression of Notch signaling components such as the recombination signal binding protein for immunoglobulin kappa J region (RBPJ), hairy and enhancer of split-1 (Hes1) or Mash1. We demonstrate that inhibition of γ-secretase through DAPT down-regulates RBPJ and Hes1, up-regulates Mash1 and results in an enhanced differentiation of BMSCs into GABAergic cells. On the other hand, RBPJ knockdown in BMSCs has no effect on Mash1 gene expression whereas Hes1 knockdown increases the expression of Mash1. Transduction of Mash1 in BMSCs also increases the expression of Hes1 but not RBPJ. Moreover, increased GABAergic differentiation in BMSCs occurs with concurrent Mash1 overexpression and Hes1-silencing. Thus, the Mash1-dependent Notch signaling pathway regulates GABAergic neuron-like differentiation of BMSCs. These results also suggest that genetic engineering of BMSCs is a useful avenue for obtaining GABAergic neuron-like donor cells for the treatment of neurological disorders.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Mash1-dependent Notch Signaling Pathway Regulates GABAergic Neuron-Like Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells

Long¹,

Luo²,

Wang³

et al. 2017

Aging and disease

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“…Innervation of DA neuron in the striatum adjusts voluntary movements and preferentially degenerates in PD. The disease is a chronic progressive neurodegenerative disorder of central nervous system with clinical motor symptoms such as akinesia, muscle rigidity, tremor, and postural instability, resulting from the extensive degeneration of dopaminergic neurons in substantia nigra pars compacta to the striatum (2345).…”

Section: Introductionmentioning

confidence: 99%

“…MSCs can be isolated from various tissues such as bone marrow, dental pulp, amnion, placenta, umbilical cord blood, and adipose tissue transdifferentiated into dopaminergic neurons in PD (11121314151617). Therefore, our goal was to generate dopaminergic neurons from human adipose derived stem cells (hADSCs) that can express TH, a specific dopaminergic neuronal marker in DA synthesis and regulation (5). For this purpose, we induced low passage (P4) of adult ADMSCs to dopaminergic neurons via direct differentiation method to investigate the specificity of the differentiated hADSCs to dopaminergic neurons.…”

Section: Introductionmentioning

confidence: 99%

Differentiation of adult human mesenchymal stem cells into dopaminergic neurons

et al. 2019

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The striatal dopamine (DA) deficiency is known as the main cause of the clinical picture of Parkinson’s disease (PD). The disease is a progressive degeneration of dopaminergic neurons in the striatum. The treatment of PD is based on compensation for the brain’s supply of DA lost by drug therapy, deep brain stimulation, surgery, gene and cell therapies. Clinical studies have focused on the utility of stem cell-based therapies in PD. Embryonic and mesenchymal stem cells (MSCs) are widely used. Recently, human adipose derived stem cells (hADSCs) have been considered as a suitable source of tissue for this purpose. In this project, hADSCs differentiated into dopaminergic neurons and the specificity of the cell preparations was examined. Human adipose tissues were collected from healthy volunteers undergoing liposuction and hADSCs were isolated by collagenase-based enzymatic method. Flow cytometry was performed using the surface cluster of differentiation (CD) markers to confirm the cell typical properties. Then hADSCs were differentiated to dopaminergic neurons in neurobasal medium in the presence of differentiation factors and confirmed by immunocytochemistry via neuronal and dopaminergic markers. The isolated hADSCs were cultured and identified by the expression of MSCs surface markers including CD90, and CD44. These cells did not express hematopoietic surface markers such as CD45 and CD14. Differentiated cells express neuronal marker NeuN and dopaminergic marker tyrosine hydroxylase (TH). It is concluded that hADSCs can be easily taken from the patient’s own body and differentiated into dopaminergic cells having a lower risk of transplant rejection.

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Therapeutic Application of Perinatal Mesenchymal Stem Cells in Nervous System Diseases

Liao¹

2019

Perinatal Stem Cells

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Differentiation of adult rat mesenchymal stem cells to GABAergic, dopaminergic and cholinergic neurons

Cited by 21 publications

References 25 publications

Mash1-dependent Notch Signaling Pathway Regulates GABAergic Neuron-Like Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells

Mash1-dependent Notch Signaling Pathway Regulates GABAergic Neuron-Like Differentiation from Bone Marrow-Derived Mesenchymal Stem Cells

Differentiation of adult human mesenchymal stem cells into dopaminergic neurons

Therapeutic Application of Perinatal Mesenchymal Stem Cells in Nervous System Diseases

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