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1.
Stem Cells Int ; 2020: 4636397, 2020.
Article in English | MEDLINE | ID: mdl-32148518

ABSTRACT

BACKGROUND: The aim of this study was to investigate the effects of human umbilical cord mesenchymal stem cell activated by curcumin (hUC-MSCs-CUR) on Parkinson's disease (PD). hUC-MSCs can differentiate into many types of adult tissue cells including dopaminergic (DA) neurons. CUR could protect DA neurons from apoptosis induced by 6-hydroxydopamine (6-OHDA). Therefore, we used the hUC-MSCs activated by CUR for the treatment of PD in an animal model. METHODS: The hUC-MSCs-CUR was transplanted into the MPTP-induced PD mouse models via the tail vein. We found that hUC-MSCs-CUR significantly improved the motor ability, increased the tyrosine hydroxylase (TH), dopamine (DA), and Bcl-2 levels, and reduced nitric oxide synthase, Bax, and cleaved caspase 3 expression in PD mice. The supernatant of hUC-MSCs-CUR (CM-CUR) was used to stimulate the SH-SY5Y cellular model of PD; cell proliferation, differentiation, TH, and neuronal-specific marker microtubular-associated protein 2 (MAP2) expressions were examined. RESULTS: Our data showed that CM-CUR significantly promoted cell proliferation and gradually increased TH and MAP2 expression in SH-SY5Y PD cells. The beneficial effects could be associated with significant increase of rough endoplasmic reticulum in the hUC-MSCs-CUR, which secretes many cytokines and growth factors beneficial for PD treatment. CONCLUSIONS: Transplantation of hUC-MSCs-CUR could show promise for improving the motor recovery of PD.

2.
Sci Rep ; 8(1): 1756, 2018 01 29.
Article in English | MEDLINE | ID: mdl-29379030

ABSTRACT

Multiple Sclerosis (MS), is a chronic inflammatory autoimmune disorder of the central nervous system that leads to chronic demyelination with axonal damage and neuronal loss. Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for MS. In the current study, we investigated the effects of MSCs derived from the human umbilical cord (UCMSC) transfected by sphingosine kinase 1 (SPK1) gene. All the results showed that transplantation of UCMSCs gene modified by SPK1 (UCMSC-SPK1) dramatically reduce the severity of neurological deficits of the experimental autoimmune encephalomyelitis (EAE) mice, paralleling by reductions in demyelination, axonal loss, and astrogliosis. UCMSC-SPK1 transplantation also could inhibit the development of natural killer (NK) responses in the spleen of EAE mice, and increase the ratio of CD4+ CD25+ FoxP3+ (Treg) T cells. Furthermore, we described that a shift in the cytokine response from Th1/Th17 to Th2 was an underlying mechanism that suppressed CNS autoimmunity. UCMSCs transfected by SPK1 gene potentially offer a novel mode for the treatment of MS, and the specific mechanism of SPK1 in treating MS/EAE.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/therapy , Mesenchymal Stem Cells/metabolism , Multiple Sclerosis/therapy , Phosphotransferases (Alcohol Group Acceptor)/genetics , Umbilical Cord/metabolism , Animals , Autoimmunity/physiology , CD4-Positive T-Lymphocytes/metabolism , Central Nervous System/metabolism , Female , Humans , Killer Cells, Natural/metabolism , Mice , Mice, Inbred C57BL , T-Lymphocytes, Regulatory/metabolism , Th17 Cells/metabolism , Transfection/methods
3.
Biomed Res Int ; 2015: 207347, 2015.
Article in English | MEDLINE | ID: mdl-25866766

ABSTRACT

Acidic (leucine-rich) nuclear phosphoprotein 32 family, member A (ANP32A), has multiple functions involved in neuritogenesis, transcriptional regulation, and apoptosis. However, whether ANP32A has an effect on the mammalian developing brain is still in question. In this study, it was shown that brain was the organ that expressed the most abundant ANP32A by human multiple tissue expression (MTE) array. The distribution of ANP32A in the different adult brain areas was diverse dramatically, with high expression in cerebellum, temporal lobe, and cerebral cortex and with low expression in pons, medulla oblongata, and spinal cord. The expression of ANP32A was higher in the adult brain than in the fetal brain of not only humans but also mice in a time-dependent manner. ANP32A signals were dispersed accordantly in embryonic mouse brain. However, ANP32A was abundant in the granular layer of the cerebellum and the cerebral cortex when the mice were growing up, as well as in the Purkinje cells of the cerebellum. The variation of expression levels and distribution of ANP32A in the developing brain would imply that ANP32A may play an important role in mammalian brain development, especially in the differentiation and function of neurons in the cerebellum and the cerebral cortex.


Subject(s)
Brain/embryology , Cell Differentiation/physiology , Gene Expression Regulation, Developmental/physiology , Neurons/metabolism , Nuclear Proteins/biosynthesis , Animals , Brain/cytology , Humans , Male , Mice , Neurons/cytology , RNA-Binding Proteins
4.
Biomed Res Int ; 2014: 909657, 2014.
Article in English | MEDLINE | ID: mdl-25276829

ABSTRACT

Parkinson's disease (PD) is a neurodegenerative movement disorder that is characterized by the progressive degeneration of the dopaminergic (DA) pathway. Mesenchymal stem cells derived from human umbilical cord (hUC-MSCs) have great potential for developing a therapeutic agent as such. HGF is a multifunctional mediator originally identified in hepatocytes and has recently been reported to possess various neuroprotective properties. This study was designed to investigate the protective effect of hUC-MSCs infected by an adenovirus carrying the HGF gene on the PD cell model induced by MPP+ on human bone marrow neuroblastoma cells. Our results provide evidence that the cultural supernatant from hUC-MSCs expressing HGF could promote regeneration of damaged PD cells at higher efficacy than the supernatant from hUC-MSCs alone. And intracellular free Ca(2+) obviously decreased after treatment with cultural supernatant from hUC-MSCs expressing HGF, while the expression of CaBP-D28k, an intracellular calcium binding protein, increased. Therefore our study clearly demonstrated that cultural supernatant of MSC overexpressing HGF was capable of eliciting regeneration of damaged PD model cells. This effect was probably achieved through the regulation of intracellular Ca(2+) levels by modulating of CaBP-D28k expression.


Subject(s)
Adenoviridae/metabolism , Hepatocyte Growth Factor/metabolism , Mesenchymal Stem Cells/metabolism , Nerve Regeneration , Parkinson Disease/pathology , Umbilical Cord/cytology , Calbindin 1/metabolism , Calcium/metabolism , Cell Line , Cell Separation , Cell Survival , Culture Media, Conditioned/pharmacology , Enzyme-Linked Immunosorbent Assay , Humans , Intracellular Space/metabolism , Mesenchymal Stem Cells/cytology , Models, Biological , Neurons , Transduction, Genetic
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