scholarly journals Effect of Astragaloside IV on Neural Stem Cell Transplantation in Alzheimer’s Disease Rat Models

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Hu Haiyan ◽  
Yang Rensong ◽  
Jin Guoqin ◽  
Zhang Xueli ◽  
Xia Huaying ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Learning And Memory ◽  
High Dose ◽  
Astragaloside Iv ◽  
Cell Based Therapy ◽  
Proliferation And Differentiation

Stem cell-based therapy is a promising treatment strategy for neurodegenerative diseases such as Alzheimer’s disease (AD). However, the mechanism underlying the maintenance of renewal and replacement capabilities of endogenous progenitor cells or engrafted stem cells in a pathological environment remains elusive. To investigate the effect of astragaloside IV (ASI) on the proliferation and differentiation of the engrafted neural stem cells (NSCs), we cultured NSCs from the hippocampus of E14 rat embryos, treated the cells with ASI, and then transplanted the cells into the hippocampus of rat AD models.In vitroexperimentation showed that 10−5 M ASI induced NSCs to differentiate intoβ-tubulin III+and GFAP+cells. NSCs transplantation into rat AD models resulted in improvements in learning and memory, especially in the ASI-treated groups. ASI treatment resulted in an increase in the number ofβ-tubulin III+cells in the hippocampus. Further investigation showed that ASI inhibited PS1 expressionin vitroandin vivo. The high-dose ASI downregulated the Notch intracellular domain, whereas the low-dose ASI increased Notch-1 and NICD. In conclusion, ASI treatment resulted in improvements in learning and memory of AD models by promoting NSC proliferation and differentiation partly through the Notch signal pathway.

scholarly journals Therapeutic Potential of Dental Pulp Stem Cell Secretome for Alzheimer’s Disease Treatment: An In Vitro Study

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Nermeen El-Moataz Bellah Ahmed ◽  
Masashi Murakami ◽  
Yujiro Hirose ◽  
Misako Nakashima
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Dental Pulp ◽  
Therapeutic Potential ◽  
Late Onset ◽  
In Vitro Study ◽  
Promising Source

The secretome obtained from stem cell cultures contains an array of neurotrophic factors and cytokines that might have the potential to treat neurodegenerative conditions. Alzheimer’s disease (AD) is one of the most common human late onset and sporadic neurodegenerative disorders. Here, we investigated the therapeutic potential of secretome derived from dental pulp stem cells (DPSCs) to reduce cytotoxicity and apoptosis caused by amyloid beta (Aβ) peptide. We determined whether DPSCs can secrete the Aβ-degrading enzyme, neprilysin (NEP), and evaluated the effects of NEP expression in vitro by quantitating Aβ-degrading activity. The results showed that DPSC secretome contains higher concentrations of VEGF, Fractalkine, RANTES, MCP-1, and GM-CSF compared to those of bone marrow and adipose stem cells. Moreover, treatment with DPSC secretome significantly decreased the cytotoxicity of Aβpeptide by increasing cell viability compared to nontreated cells. In addition, DPSC secretome stimulated the endogenous survival factor Bcl-2 and decreased the apoptotic regulator Bax. Furthermore, neprilysin enzyme was detected in DPSC secretome and succeeded in degradingAβ1–42in vitro in 12 hours. In conclusion, our study demonstrates that DPSCs may serve as a promising source for secretome-based treatment of Alzheimer’s disease.

scholarly journals Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and Alzheimer’s Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-30 ◽  
Author(s):  
Ankit Tandon ◽  
Sangh Jyoti Singh ◽  
Rajnish Kumar Chaturvedi
Keyword(s):  
Multiple Sclerosis ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Stem Cell ◽  
Therapeutic Effects ◽  
Potential Candidate ◽  
Behavioral Deficits ◽  
Cell Therapies ◽  
Proliferation And Differentiation

Alzheimer’s disease (AD) and multiple sclerosis are major neurodegenerative diseases, which are characterized by the accumulation of abnormal pathogenic proteins due to oxidative stress, mitochondrial dysfunction, impaired autophagy, and pathogens, leading to neurodegeneration and behavioral deficits. Herein, we reviewed the utility of plant polyphenols in regulating proliferation and differentiation of stem cells for inducing brain self-repair in AD and multiple sclerosis. Firstly, we discussed the genetic, physiological, and environmental factors involved in the pathophysiology of both the disorders. Next, we reviewed various stem cell therapies available and how they have proved useful in animal models of AD and multiple sclerosis. Lastly, we discussed how polyphenols utilize the potential of stem cells, either complementing their therapeutic effects or stimulating endogenous and exogenous neurogenesis, against these diseases. We suggest that polyphenols could be a potential candidate for stem cell therapy against neurodegenerative disorders.

Amniotic Stem Cell-Conditioned Media for the Treatment of Nerve and Muscle Pathology: A Systematic Review

2021 ◽  
Author(s):  
Chukwuweike Gwam ◽  
Ahmed Emara ◽  
Nequesha Mohamed ◽  
Noor Chughtai ◽  
Johannes Plate ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Cell Damage ◽  
Conditioned Media ◽  
Nerve Tissue ◽  
Muscle Pathology ◽  
Loss Of Function ◽  
Cell Based Therapy

Muscle and nerve tissue damage can elicit a significant loss of function and poses as a burden for patients and healthcare providers. Even for tissues, such as the peripheral nerve and skeletal muscle, that harbor significant regenerative capacity, innate regenerative processes often lead to less than optimal recovery and residual loss of function. The reasons for poor regeneration include significant cell damage secondary to oxidative stress, poor recruitment of resident stem cells, and an unfavorable microenvironment for tissue regeneration. Stem cell-based therapy was once thought as a potential therapy in tissue regeneration, due to its self-renewal and multipotent capabilities. Early advocates for cellular-based therapy pointed to the pluripotent nature of stem cells, thus eluding to its ability to differentiate into resident cells as the source of its regenerative capability. However, increasing evidence has revealed a lack of engraftment and differentiation of stem cells, thereby pointing to stem cell paracrine activity as being responsible for its regenerative potential. Stem cell-conditioned media houses biomolecular factors that portray significant regenerative potential. Amniotic-derived stem cell-conditioned media (AFS-CM) has been of particular interest because of its ease of allocation and in vitro culture. The purpose of this review is to report the results of studies that assess the role of AFS-CM for nerve and muscle conditions. In this review, we will cover the effects of AFS-CM on cellular pathways, genes, and protein expression for different nerve and muscle cell types.

Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cells (Admscs) and/or Taurine in Aluminum Chloride-Induced Alzheimer's Disease Rat Model

2021 ◽  
Author(s):  
Mohamed Hosney ◽  
Alaa Sakraan ◽  
Aman Asaad ◽  
Mervat El-Deftar ◽  
Emad Elzayat
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Cell Activation ◽  
Therapeutic Potential ◽  
Brain Homogenate ◽  
Oxidative Stress Marker

Abstract Alzheimer's disease (AD) is the most prevalent type of dementia characterized by its progression, neurobehavioral and neuro-pathological characteristics, leading to a diverse neuronal loss. Adipose-derived mesenchymal stem cells (ADMSCs) have previously proved potential role in preventing the pathogenesis of several neurodegenerative disorders, so regarded as a promising new approach for AD regenerative therapy. Taurine was found to enhance stem cell activation and propagation yielding a higher concentration of neural progenitors and stem cells, and aid to lessen the number of activated microglia leading to down-regulated inflammation in vitro. The present study aimed to investigate the possible therapeutic potential of ADMSCs and/or taurine in treating AD rat model. It was planned to include three successive phases; induction, withdrawal, and therapeutic phases. Fifty male Wistar rats were divided into 2 main groups: control (C) group and AD model group. Behavioral changes, as manifested by the T-Maze experiment, had been recorded. β-amyloid levels had been measured in brain homogenate and serum by ELISA. Oxidative stress marker (MDA), and anti-oxidant enzymes activity (SOD, GSH, and CAT) in brain, as well as serum acetylcholine esterase activity were spectrophotometrically determined. Pro-apoptotic (p53 and Bax) and anti-apoptotic (Bcl2) gene expression in brain were evaluated using RT-qPCR. The histopathological alterations in brain tissues were also observed. The present study proved the potential therapeutic ability of ADMSCs and/or taurine in alleviating the adverse pathological changes induced by AlCl3 in AD rat model at both physiological and molecular levels.

Stem cells in brain diseases: From cell replacement to disease modeling

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Nina Kosi ◽  
Dinko Mitrečić
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Disease Modeling ◽  
Neurological Diseases ◽  
Rapid Development ◽  
Modern Society ◽  
Brain Diseases ◽  
Stem Cell Technology ◽  
Cell Based Therapy

AbstractNeurological diseases are recognized as one of the most significant burdens of the modern society. Therefore, a new therapeutic approach applicable to nervous system represents priority of today’s medicine. A rapid development of stem cell technology in the last two decades introduced a possibility to regenerate disease-affected nervous tissue. In this vein, stem cells are envisioned as a replacement for lost neurons, a source of trophic support, a therapeutic vehicle, and as a tool for in vitro modeling. This article reviews the current concepts in stem cell-based therapy of neurological diseases and comments ongoing efforts aiming at clinical translation.

Systematic Intracellular Biocompatibility Assessments of Superparamagnetic Iron Oxide Nanoparticles in Human Umbilical Cord Mesenchyme Stem Cells in Testifying Its Reusability for Inner Cell Tracking by MRI

2019 ◽  
Vol 15 (11) ◽  
pp. 2179-2192
Author(s):  
Yuanyuan Xie ◽  
Wei Liu ◽  
Bing Zhang ◽  
Bin Wang ◽  
Liudi Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Cell Tracking ◽  
Superparamagnetic Iron Oxide ◽  
Human Umbilical Cord ◽  
Cell Based Therapy

Until now, there is no effective method for tracking transplanted stem cells in human. Ruicun (RC) is a new ultra-small SPIONs agent that has been approved by China Food and Drug Administration for iron supplementation but not as a stem cell tracer in clinic. In this study, we demonstrated magnetic resonance imaging-based tracking of RC-labeled human umbilical cord derived mesenchymal stem cells (MSCs) transplanted to locally injured site of rat spinal cords. We then comprehensively evaluated the safety and quality of the RC-labeled MSCs under good manufacturing practicecompliant conditions, to investigate the feasibility of SPIONs for inner tracking in stem cell-based therapy (SCT). Our results showed that RC labeling at appropriate dose (200 μg/mL) did not have evident impacts on characteristics of MSCs in vitro, demonstrating safety, non-carcinogenesis, and non-tissue inflammation in vivo. The systematic assessments of intracellular biocompatibility indicated that the RC labeled MSCs met with mandatory requirements and standards for law-regulation systems regarding SCT, facilitating translation of cell-tracking technologies to clinical trials.

296 PRODUCTION OF HEMIZYGOUS AND HOMOZYGOUS EMBRYONIC STEM CELL-DERIVED NEURAL PROGENITOR CELLS FROM THE TRANSGENIC ALZHEIMER GÖTTINGEN MINIPIG

2011 ◽  
Vol 23 (1) ◽  
pp. 245
Author(s):  
V. J. Hall ◽  
J. Jakobsen ◽  
A. Gunnarsson ◽  
M. Schmidt ◽  
A. Lund Jørgensen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Cell Lines ◽  
Real Time Pcr ◽  
Embryonic Stem ◽  
Neural Progenitor ◽  
Novel Drugs

Alzheimer’s disease is the most prevalent cause of dementia and afflicts ∼26 million people worldwide. There are currently no cures for this disease. Production of in vitro models of the disease would be extremely useful for studying disease mechanisms and for potential screening of novel drugs. In this study we produced 2 hemizygote and 2 homozygote embryonic stem cell-derived neural progenitor cell lines from Day 8 transgenic blastocysts carrying a human gene linked to early-onset Alzheimer’s disease [Swedish mutation of the amyloid precursor protein (hAPPsw)]. Following onset of spontaneous oestrus, a mating of hAPPsw± × hAPPsw± Göttingen transgenic progeny was performed. Eight days after the first of 2 matings, embryos were flushed from the tip of both cornuas of the gilt under surgical anaesthesia. A total of 6 blastocysts were obtained and 7 corpora lutei recorded. Blastocysts were transported for 4 h in porcine zygote medium 3 (PZM-3) in hypoxic, humidified conditions at 39°C to the cell laboratory. Compact epiblasts were mechanically isolated from the embryo using insulin needles and cultured on inactivated mouse embryonic fibroblasts in embryonic stem cell medium, supplemented with 20 ng mL–1 human recombinant basic fibroblast growth factor (Prospec) and 20 ng mL–1 human recombinant Activin A (Prospec), for a period of 5 days in hypoxic conditions at 39°C. Five of the 6 epiblasts expanded to form embryonic stem-cell-like outgrowth colonies. These were cut into small colonies and plated on MS5 murine stromal cells to induce spontaneous neural differentiation in DMEM medium containing 15% knockout serum replacement. Neuronal rosette-like structures were identified from Day 10 of differentiation onward. Six rosette structures were mechanically isolated from 4 outgrowths and plated in serum-free conditions on Matrigel-coated dishes. Two of the 6 lines failed to proliferate beyond passage 2. The 4 remaining cell lines have currently been cultured to passage 7. These lines were analysed at passage 5 by comparative real-time PCR and found to be positive for the neural progenitor markers VIMENTIN, SOX2, NESTIN PAX6, MUSASHI; other neural markers BETAIIITUBULIN and NCAM; and the astrocyte marker, GFAP. These lines were also subjected to analysis by immunocytochemistry and found to express SOX2, VIMENTIN, and NESTIN. Further genotyping by comparative real-time PCR using primers designed to target the hAPPsw gene revealed that 2 lines carried a single copy of hAPPsw and 2 lines carried 2 copies of hAPPsw. The expression levels of the hAPPsw transgene in these cell lines were determined using quantitative PCR. These cell lines are currently being investigated for their ability to differentiate into cholinergic neurons and for their expression of hyperphosphorylated TAU and β-Amyloid secretion. These cell lines will be potentially relevant for the in vitro study of amyloid precursor protein accumulation in neural cells and its role in cell death, as well as for potential screening of novel drugs for Alzheimer’s disease.

scholarly journals Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells

2017 ◽  
Vol 43 (3) ◽  
pp. 891-904 ◽  
Author(s):  
Jie He ◽  
Guang-ping Ruan ◽  
Xiang Yao ◽  
Ju-fen Liu ◽  
Xiang-qing Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Intravenous Infusion ◽  
Dose Group ◽  
High Dose ◽  
Human Umbilical Cord ◽  
Cynomolgus Monkeys ◽  
Cell Based Therapy

Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3+ and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 107/kg, which is 10 times of that in clinical human use.

scholarly journals Icariin Promotes Survival, Proliferation, and Differentiation of Neural Stem Cells In Vitro and in a Rat Model of Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Denglei Ma ◽  
Lihong Zhao ◽  
Li Zhang ◽  
Yali Li ◽  
Lan Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rat Model ◽  
Basal Forebrain ◽  
Chinese Herb ◽  
Cholinergic Neurons ◽  
Model Of Alzheimer’S Disease ◽  
Promising Therapeutic Approach ◽  
Proliferation And Differentiation

Alzheimer’s disease (AD) involves the degeneration of cholinergic neurons in the basal forebrain. Neural stem cell (NSC) transplantation has emerged as a promising therapeutic approach for treating AD. Icariin (ICA) is the main active component in Epimedium, a traditional Chinese herb. The purpose of the present study was to investigate the effects and mechanisms of ICA on the proliferation and differentiation of NSCs in the basal forebrain of a fimbria-fornix transection (FFT) rat model. In the present study, ICA promoted the survival, proliferation, and migration of NSCs in vitro. In FFT rats, ICA promoted the proliferation and differentiation of NSCs into neurons and increased the number of cholinergic neurons in the MS and VDB of the basal forebrain. These results suggest that combination therapy of ICA oral administration and NSC transplantation may provide a new potential and effective approach for AD therapy.

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