scholarly journals Hydrogen Peroxide-Preconditioned Human Adipose-Derived Stem Cells Enhance the Recovery of Oligodendrocyte-Like Cells after Oxidative Stress-Induced Damage

2020 ◽  
Vol 21 (24) ◽  
pp. 9513
Author(s):  
Patricia Garrido-Pascual ◽  
Ana Alonso-Varona ◽  
Begoña Castro ◽  
María Burón ◽  
Teodoro Palomares
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Therapeutic Potential ◽  
Mild Stress ◽  
Adipose Derived Stem Cells ◽  
Vitro Model ◽  
Novel Strategy ◽  
The One ◽  
Cell Conditioned Medium

Oxidative stress associated with neuroinflammation is a key process involved in the pathophysiology of neurodegenerative diseases, and therefore, has been proposed as a crucial target for new therapies. Recently, the therapeutic potential of human adipose-derived stem cells (hASCs) has been investigated as a novel strategy for neuroprotection. These cells can be preconditioned by exposing them to mild stress in order to improve their response to oxidative stress. In this study, we evaluate the therapeutic potential of hASCs preconditioned with low doses of H2O2 (called HC016 cells) to overcome the deleterious effect of oxidative stress in an in vitro model of oligodendrocyte-like cells (HOGd), through two strategies: i, the culture of oxidized HOGd with HC016 cell-conditioned medium (CM), and ii, the indirect co-culture of oxidized HOGd with HC016 cells, which had or had not been exposed to oxidative stress. The results demonstrated that both strategies had reparative effects, oxidized HC016 cell co-culture being the one associated with the greatest recovery of the damaged HOGd, increasing their viability, reducing their intracellular reactive oxygen species levels and promoting their antioxidant capacity. Taken together, these findings support the view that HC016 cells, given their reparative capacity, might be considered an important breakthrough in cell-based therapies.

scholarly journals Oxidative Stress in Alzheimer’s Disease: In Vitro Therapeutic Effect of Amniotic Fluid Stem Cells Extracellular Vesicles

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Martina Gatti ◽  
Manuela Zavatti ◽  
Francesca Beretti ◽  
Daniela Giuliani ◽  
Eleonora Vandini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Amniotic Fluid ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Amniotic Fluid Stem Cells ◽  
Vitro Model

Alzheimer’s disease (AD) is characterized by abnormal protein aggregation, deposition of extracellular β-amyloid proteins (Aβ), besides an increase of oxidative stress. Amniotic fluid stem cells (AFSCs) should have a therapeutic potential for neurodegenerative disorders, mainly through a paracrine effect mediated by extracellular vesicles (EV). Here, we examined the effect of EV derived from human AFSCs (AFSC-EV) on the disease phenotypes in an AD neuron primary culture. We observed a positive effect of AFSC-EV on neuron morphology, viability, and Aβ and phospho-Tau levels. This could be due to the apoptotic and autophagic pathway modulation derived from the decrease in oxidative stress. Indeed, reactive oxygen species (ROS) were reduced, while GSH levels were enhanced. This modulation could be ascribed to the presence of ROS regulating enzymes, such as SOD1 present into the AFSC-EV themselves. This study describes the ROS-modulating effects of extracellular vesicles alone, apart from their deriving stem cell, in an AD in vitro model, proposing AFSC-EV as a therapeutic tool to stop the progression of AD.

scholarly journals Enhanced Therapeutic Potential of the Secretome Released from Adipose-Derived Stem Cells by PGC-1α-Driven Upregulation of Mitochondrial Proliferation

2019 ◽  
Vol 20 (22) ◽  
pp. 5589
Author(s):  
Jaeim Lee ◽  
Ok-Hee Kim ◽  
Sang Chul Lee ◽  
Kee-Hwan Kim ◽  
Jin Sun Shin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Liver Injury ◽  
Therapeutic Potential ◽  
Tissue Expression ◽  
In Vitro Models ◽  
Peroxisome Proliferator ◽  
Adipose Derived Stem Cells ◽  
Peroxisome Proliferator Activated Receptor

Peroxisome proliferator activated receptor λ coactivator 1α (PGC-1α) is a potent regulator of mitochondrial biogenesis and energy metabolism. In this study, we investigated the therapeutic potential of the secretome released from the adipose-derived stem cells (ASCs) transfected with PGC-1α (PGC-secretome). We first generated PGC-1α-overexpressing ASCs by transfecting ASCs with the plasmids harboring the gene encoding PGC-1α. Secretory materials released from PGC-1α-overexpressing ASCs were collected and their therapeutic potential was determined using in vitro (thioacetamide (TAA)-treated AML12 cells) and in vivo (70% partial hepatectomized mice) models of liver injury. In the TAA-treated AML12 cells, the PGC-secretome significantly increased cell viability, promoted expression of proliferation-related markers, such as PCNA and p-STAT, and significantly reduced the levels of reactive oxygen species (ROS). In the mice, PGC-secretome injections significantly increased liver tissue expression of proliferation-related markers more than normal secretome injections did (p < 0.05). We demonstrated that the PGC-secretome does not only have higher antioxidant and anti-inflammatory properties, but also has the potential of significantly enhancing liver regeneration in both in vivo and in vitro models of liver injury. Thus, reinforcing the mitochondrial antioxidant potential by transfecting ASCs with PGC-1α could be one of the effective strategies to enhance the therapeutic potential of ASCs.

scholarly journals Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Haoyu Wu ◽  
Zhi Peng ◽  
Ying Xu ◽  
Zixuan Sheng ◽  
Yanshan Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
High Efficiency ◽  
Therapeutic Potential ◽  
Immunohistochemical Analysis ◽  
Fluorescent Labeling ◽  
Knee Joints ◽  
Adipose Derived Stem Cells ◽  
Promising Alternative

Abstract Background Osteoarthritis (OA), a prevalent degenerative disease characterized by degradation of extracellular matrix (ECM), still lacks effective disease-modifying therapy. Mesenchymal stem cells (MSCs) transplantation has been regarded as the most promising approach for OA treatment while engrafting cells alone might not be adequate for effective regeneration. Genetic modification has been used to optimize MSC-based therapy; however, there are still significant limitations that prevent the clinical translation of this therapy including low efficacy and safety concerns. Recently, chemically modified mRNA (modRNA) represents a promising alternative for the gene-enhanced MSC therapy. In this regard, we hypothesized that adipose derived stem cells (ADSCs) engineered with modRNA encoding insulin-like growth factor 1 (IGF-1) were superior to native ADSCs on ameliorating OA development. Methods Mouse ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IGF-1 modRNA engineered ADSCs (named as IGF-1-ADSCs) on chondrocytes. Finally, we evaluated the cell retention and chondroprotective effect of IGF-1-ADSCs in vivo using fluorescent labeling, histology and immunohistochemistry. Results modRNA transfected mouse ADSCs with high efficiency (85 ± 5%) and the IGF-1 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IGF-1 protein. In vitro, IGF-1-ADSCs induced increased anabolic markers expression of chondrocytes in inflammation environment compared to untreated ADSCs. In a murine OA model, histological and immunohistochemical analysis of knee joints harvested at 4 weeks and 8 weeks after OA induction suggested IGF-1-ADSCs had superior therapeutic effect over native ADSCs demonstrated by lower histological OARSI score and decreased loss of cartilage ECM. Conclusions These findings collectively supported the therapeutic potential of IGF-1-ADSCs for clinical OA management and cartilage repair.

scholarly journals Extracts from Myrtle Liqueur Processing Waste Modulate Stem Cells Pluripotency under Stressing Conditions

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Sara Cruciani ◽  
Sara Santaniello ◽  
Angela Fadda ◽  
Luana Sale ◽  
Giorgia Sarais ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Stem Cell ◽  
Pharmaceutical Preparations ◽  
Ros Production ◽  
Adipose Derived Stem Cells ◽  
Epigenetic Changes ◽  
Processing Waste ◽  
Stem Cell Pluripotency

Nutraceuticals present in food are molecules able to exert biological activity for the prevention and treatment of various diseases, in form of pharmaceutical preparations, such as capsules, cream, or pills. Myrtus communis L. is a spontaneous Mediterranean evergreen shrub, widely known for the liqueur obtained from its berries rich in phytochemicals such as tannins and flavonoids. In the present study, we aimed to evaluate the properties of myrtle byproducts, residual of the industrial liqueur processing, in Adipose-derived stem cells (ADSCs) induced at oxidative stress by in vitro H2O2 treatment. Cells were exposed for 12-24 and 48h at treatment with extracts and then senescence-induced. ROS production was then determined. The real-time PCR was performed to evaluate the expression of inflammatory cytokines and sirtuin-dependent epigenetic changes, as well the modifications in terms of stem cell pluripotency. The β-galactosidase assay was conducted to analyze stem cell senescence after treatment. Our results show that industrial myrtle byproducts retain a high antioxidant and antisenescence activity, protecting cells from oxidative stress damages. The results obtained suggest that residues from myrtle liqueur production could be used as resource in formulation of food supplements or pharmaceutical preparations with antioxidant, antiaging, and anti-inflammatory activity.

scholarly journals Extracellular Vesicles of Adipose-Derived Stem Cells Promote the Healing of Traumatized Achilles Tendons

2021 ◽  
Vol 22 (22) ◽  
pp. 12373
Author(s):  
Shih-Heng Chen ◽  
Zhi-Yu Chen ◽  
Ya-Hsuan Lin ◽  
Shih-Hsien Chen ◽  
Pang-Yun Chou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mechanical Strength ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Early Stage ◽  
Adipose Derived Stem Cells ◽  
Tendon Regeneration ◽  
And Migration ◽  
Proliferation And Migration

Healing of ruptured tendons remains a clinical challenge because of its slow progress and relatively weak mechanical force at an early stage. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have therapeutic potential for tissue regeneration. In this study, we isolated EVs from adipose-derived stem cells (ADSCs) and evaluated their ability to promote tendon regeneration. Our results indicated that ADSC-EVs significantly enhanced the proliferation and migration of tenocytes in vitro. To further study the roles of ADSC-EVs in tendon regeneration, ADSC-EVs were used in Achilles tendon repair in rabbits. The mechanical strength, histology, and protein expression in the injured tendon tissues significantly improved 4 weeks after ADSC-EV treatment. Decorin and biglycan were significantly upregulated in comparison to the untreated controls. In summary, ADSC-EVs stimulated the proliferation and migration of tenocytes and improved the mechanical strength of repaired tendons, suggesting that ADSC-EV treatment is a potential highly potent therapeutic strategy for tendon injuries.

scholarly journals Intra-articular injection of PDGF-BB explored in a novel in vitro model mobilizes mesenchymal stem cells from the synovium into synovial fluid in rats

2021 ◽  
Author(s):  
Kentaro Endo ◽  
Kiyotaka Horiuchi ◽  
Hisako Katano ◽  
Nobutake Ozeki ◽  
Yuriko Sakamaki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Synovial Fluid ◽  
In Vitro Model ◽  
Practical Application ◽  
Collagen Hydrogel ◽  
Vitro Model ◽  
The One

Abstract Background Drugs that can induce mesenchymal stem cell (MSC) mobilization from synovium into synovial fluid will enable regenerative medicine in joints without use of exogenous MSCs. An in vitro synovial MSC migration model had previously been developed for screening but had problems in practical application. We herein developed a novel in vitro model, explored cytokines for synovial MSC mobilization with this model, and verified whether MSCs in synovial fluid increase following intra-articular injection of the cytokine. Methods Human synovial MSCs embedded in a mixture of Matrigel and type 1 collagen hydrogel were placed on a culture insert and then put in medium containing migration factor. Of the six cytokines, we identified the one that mobilizes the highest number of MSCs. PDGF-BB or PBS was injected into rat knees, and 48 h later, synovial fluid was collected and cultured. The cells were examined for MSC properties. Results PDGF-BB was the most effective for synovial MSC mobilization among six cytokines. The effect of PDGF-BB was inhibited by a PRGFR inhibitor. Injection of PDGF-BB into rat knees increased colony-forming cells in the synovial fluid. These cells had surface epitopes and multipotency comparable to MSCs and a higher capacity for proliferation, colony formation, and chondrogenesis. Conclusions This novel in vitro model recapitulated the migration of MSCs from synovium into synovial fluid. Our exploration of cytokines revealed that PDGF-BB strongly induced in vitro synovial MSC migration, while intra-articular injection of PDGF-BB increased in vivo MSC numbers in synovial fluid in rats.

scholarly journals Robot technology identifies a Parkinsonian therapeutics repurpose to target stem cells of glioblastoma

CNS Oncology ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. CNS58 ◽  
Author(s):  
Andres Vargas-Toscano ◽  
Dilaware Khan ◽  
Ann-Christin Nickel ◽  
Michael Hewera ◽  
Marcel Alexander Kamp ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mode Of Action ◽  
Drug Testing ◽  
Therapeutic Potential ◽  
Cancer Models ◽  
Testing Facility ◽  
Action Analysis ◽  
Vitro Model ◽  
Stem Cell Hierarchy

Aim: Glioblastoma is a heterogeneous lethal disease, regulated by a stem-cell hierarchy and the neurotransmitter microenvironment. The identification of chemotherapies targeting individual cancer stem cells is a clinical need. Methodology: A robotic workstation was programmed to perform a drug concentration to cell-growth analysis on an in vitro model of glioblastoma stem cells (GSCs). Mode-of-action analysis of the selected top substance was performed with manual repetition assays and acquisition of further parameters. Results: We identified 22 therapeutic potential substances. Three suggested a repurpose potential of neurotransmitter signal-modulating agents to target GSCs, out of which the Parkinson's therapeutic trihexyphenidyl was most effective. Manual repetition assays and initial mode of action characterization revealed suppression of cell proliferation, cell cycle and survival. Conclusion: Anti-neurotransmitter signaling directed therapy has potential to target GSCs. We established a drug testing facility that is able to define a mid-scale chemo responsome of in vitro cancer models, possibly also suitable for other cell systems.

scholarly journals Human Adipose-Derived Stem Cells in Madelung’s Disease: Morphological and Functional Characterization

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 44
Author(s):  
Federica Caponnetto ◽  
Ivana Manini ◽  
Michela Bulfoni ◽  
Nicola Zingaretti ◽  
Giovanni Miotti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Kinetic ◽  
In Vitro Model ◽  
Adipogenic Differentiation ◽  
Functional Characterization ◽  
Adipose Derived Stem Cells ◽  
Differentiation Potential ◽  
Molecular Alterations ◽  
Vitro Model

Madelung Disease (MD) is a syndrome characterized by the accumulation of aberrant symmetric adipose tissue deposits. The etiology of this disease is yet to be elucidated, even though the presence of comorbidities, either genetic or environmental, has been reported. For this reason, establishing an in vitro model for MD is considered crucial to get insights into its physiopathology. We previously established a protocol for isolation and culture of stem cells from diseased tissues. Therefore, we isolated human adipose-derived stem cells (ASC) from MD patients and compared these cells with those isolated from healthy subjects in terms of surface phenotype, growth kinetic, adipogenic differentiation potential, and molecular alterations. Moreover, we evaluated the ability of the MD-ASC secretome to affect healthy ASC. The results reported a difference in the growth kinetic and surface markers of MD-ASC compared to healthy ASC but not in adipogenic differentiation. The most commonly described mitochondrial mutations were not observed. Still, MD-ASC secretome was able to shift the healthy ASC phenotype to an MD phenotype. This work provides evidence of the possibility of exploiting a patient-based in vitro model for better understanding MD pathophysiology, possibly favoring the development of novel target therapies.

scholarly journals Characterization of human adipose-derived stem cells

2012 ◽  
Vol 27 (7) ◽  
pp. 471-476 ◽  
Author(s):  
Silvana Gaiba ◽  
Lucimar Pereira de França ◽  
Jerônimo Pereira de França ◽  
Lydia Masako Ferreira
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Chondrogenic Differentiation ◽  
Therapeutic Potential ◽  
Culture Conditions ◽  
In Vitro Cultivation ◽  
Neural Cells ◽  
Adipose Derived Stem Cells ◽  
Differentiation Potential

PURPOSE: There is a growing scientific interest in the plasticity and therapeutic potential of adipose-derived stem cells (ASCs), which are multipotent and abundant in adipose tissue and can differentiate in vitro into multiple lineages, including adipocytes, chondrocytes, osteoblasts, neural cells, endothelial cells and cardiomyocytes. The aim of this study was to isolate, cultivate and identify ASCs. METHODS: Human adipose precursor cells were obtained from subcutaneous abdominal tissue. Recently dispersed cells were separated by density centrifugation gradient, cultured and then analyzed. RESULTS: Human ASCs were able to replicate in our culture conditions. The cells maintained their phenotypes throughout the studied period on different passages confirming they suitability for in vitro cultivation. We also induced their adipogenic, osteogenic and chondrogenic differentiation, verifying their mesenchymal stem cells potentiality in vitro. Flow cytometry results showed that these cells expressed CD73, CD90 and CD105, (mesenchymal stem-cells markers), contrasting with the lack of expression of CD16, CD34 and CD45 (hematopoietic cells markers). CONCLUSION: It was possible to isolate human adipose-derived stem cells by in vitro cultivation without adipogenic induction, maintaining their functional integrity and high proliferation levels. The cells demonstrated adipogenic, osteogenic and chondrogenic differentiation potential in vitro.

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