SKP-SCs transplantation alleviates 6-OHDA-induced dopaminergic neuronal injury by modulating autophagy

AbstractParkinson’s disease is a common neurodegenerative disease. Cell transplantation is a promising therapeutic option for improving the survival and function of dopaminergic neurons, but the mechanisms underlying the interaction between the transplanted cells and the recipient neurons remain to be studied. In this study, we investigated the effects of skin precursor cell-derived Schwann cells (SKP-SCs) directly cocultured with 6-OHDA-injured dopaminergic neurons in vitro and of SKP-SCs transplanted into the brains of 6-OHDA-induced PD mice in vivo. In vitro and in vivo studies revealed that SKP-SCs could reduce the damage to dopaminergic neurons by enhancing self-autophagy and modulating neuronal autophagy. Thus, the present study provides the first evidence that cell transplantation mitigates 6-OHDA-induced damage to dopaminergic neurons by enhancing self-autophagy, suggesting that earlier transplantation of Schwann cells might help alleviate the loss of dopaminergic neurons.

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Alcohol-and-HIV-Induced Lysosomal Dysfunction Regulates Extracellular Vesicles Secretion in Vitro and in Liver-Humanized Mice

Biology ◽

10.3390/biology10010029 ◽

2021 ◽

Vol 10 (1) ◽

pp. 29

Author(s):

Raghubendra Singh Dagur ◽

Moses New-Aaron ◽

Murali Ganesan ◽

Weimin Wang ◽

Svetlana Romanova ◽

...

Keyword(s):

Oxidative Stress ◽

Extracellular Vesicles ◽

Treated Group ◽

Human Hepatocytes ◽

In Vivo Studies ◽

People Living With Hiv ◽

Humanized Mouse Model ◽

And Function

Background: Alcohol abuse is common in people living with HIV-1 and dramaticallyenhances the severity of HIV-induced liver damage by inducing oxidative stress and lysosomaldysfunction in the liver cells. We hypothesize that the increased release of extracellular vesicles(EVs) in hepatocytes and liver humanized mouse model is linked to lysosome dysfunction. Methods:The study was performed on primary human hepatocytes and human hepatoma RLWXP-GFP (Huh7.5 cells stably transfected with CYP2E1 and XPack-GFP) cells and validated on ethanol-fed liverhumanizedfumarylacetoacetate hydrolase (Fah)-/-, Rag2-/-, common cytokine receptor gamma chainknockout (FRG-KO) mice. Cells and mice were infected with HIV-1ADA virus. Results: We observedan increase in the secretion of EVs associated with a decrease in lysosomal activity and expressionof lysosomal-associated membrane protein 1. Next-generation RNA sequencing of primary humanhepatocytes revealed 63 differentially expressed genes, with 13 downregulated and 50 upregulatedgenes in the alcohol–HIV-treated group. Upstream regulator analysis of differentially expressedgenes through Ingenuity Pathway Analysis identified transcriptional regulators affecting downstreamgenes associated with increased oxidative stress, lysosomal associated disease, and function andEVs biogenesis. Our in vitro findings were corroborated by in vivo studies on human hepatocytetransplantedhumanized mice, indicating that intensive EVs’ generation by human hepatocytes andtheir secretion to serum was associated with increased oxidative stress and reduction in lysosomalactivities triggered by HIV infection and ethanol diet. Conclusion: HIV-and-ethanol-metabolisminducedEVs release is tightly controlled by lysosome status in hepatocytes and participates in thedevelopment of double-insult-induced liver injury.

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N-Cadherin Upregulation Promotes the Neurogenic Differentiation of Menstrual Blood-Derived Endometrial Stem Cells

Stem Cells International ◽

10.1155/2018/3250379 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Yanli Liu ◽

Fen Yang ◽

Shengying Liang ◽

Qing Liu ◽

Sulei Fu ◽

...

Keyword(s):

Stem Cells ◽

Peripheral Nerve ◽

Therapeutic Option ◽

In Vivo Studies ◽

Menstrual Blood ◽

Neurogenic Differentiation ◽

Endometrial Stem Cells ◽

Medical Disorders

Peripheral nerve injuries are typically caused by either trauma or medical disorders, and recently, stem cell-based therapies have provided a promising treatment approach. Menstrual blood-derived endometrial stem cells (MenSCs) are considered an ideal therapeutic option for peripheral nerve repair due to a noninvasive collection procedure and their high proliferation rate and immunological tolerance. Here, we successfully isolated MenSCs and examined their biological characteristics including their morphology, multipotency, and immunophenotype. Subsequent in vitro studies demonstrated that MenSCs express high levels of neurotrophic factors, such as NT3, NT4, BDNF, and NGF, and are capable of transdifferentiating into glial-like cells under conventional induction conditions. Moreover, upregulation of N-cadherin (N-cad) mRNA and protein expression was observed after neurogenic differentiation. In vivo studies clearly showed that N-cad knockdown via in utero electroporation perturbed the migration and maturation of mouse neural precursor cells (NPCs). Finally, a further transfection assay also confirmed that N-cad upregulation in MenSCs results in the expression of S100. Collectively, our results confirmed the paracrine effect of MenSCs on neuroprotection as well as their potential for transdifferentiation into glial-like cells and demonstrated that N-cad upregulation promotes the neurogenic differentiation of MenSCs, thereby providing support for transgenic MenSC-based therapy for peripheral nerve injury.

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Nanoparticles at the neurovascular unit: In vitro and in vivo studies to assess the blood-brain barrier permeability and function

Vascular Pharmacology ◽

10.1016/j.vph.2017.12.023 ◽

2018 ◽

Vol 103-105 ◽

pp. 55-56

Author(s):

G. Forcaia ◽

R. Dal Magro ◽

B. Albertini ◽

P. Blasi ◽

F. Re ◽

...

Keyword(s):

Blood Brain Barrier ◽

Neurovascular Unit ◽

Brain Barrier ◽

In Vivo Studies ◽

Barrier Permeability ◽

Blood Brain Barrier Permeability ◽

Brain Barrier Permeability ◽

And Function

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Structure-function relationships in mitochondrial transcriptional condensates

10.1101/2021.12.30.474545 ◽

2022 ◽

Author(s):

Marina Feric ◽

Azadeh Sarfallah ◽

Furqan Dar ◽

Dmitry Temiakov ◽

Rohit V Pappu ◽

...

Keyword(s):

Structure Function ◽

Computational Modelling ◽

In Vivo Studies ◽

Bulk Solution ◽

The Core ◽

Functional Consequences ◽

Cellular Machinery ◽

And Function

Phase separation organizes many membraneless structures in cells. The functional consequences of concentrating cellular machinery into biomolecular condensates, however, is largely unclear. Here, we use in vitro reconstitutions, in vivo studies, and computational modelling to uncover structure-function relationships of mitochondrial (mt-) transcriptional condensates. In vitro, we find that the core mt-transcription machinery — consisting of POLRMT, TFAM, TFB2M, and DNA — forms viscoelastic, multi-phasic condensates. Strikingly, the rates of condensate-mediated transcription are considerably lower than equivalent reactions in bulk solution. Dampened rates are associated with reduced diffusivities of components that become kinetically arrested in non-equilibrium, vesicular condensates. Perturbation of mt-components in vivo and computational simulations recapitulate the transcription-dependent reorganizations observed in vitro. Our findings demonstrate close, bidirectional interdependence between structure and function of transcriptional condensates.

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Structure and function of anhydride-modified forms of human insulin: In silico, in vitro and in vivo studies

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2016.09.030 ◽

2017 ◽

Vol 96 ◽

pp. 342-350 ◽

Cited By ~ 4

Author(s):

Maryam Chinisaz ◽

Azadeh Ebrahim-Habibi ◽

Ahmad-Reza Dehpour ◽

Parichehreh Yaghmaei ◽

Kazem Parivar ◽

...

Keyword(s):

Human Insulin ◽

In Silico ◽

Structure And Function ◽

In Vivo Studies ◽

And Function ◽

Modified Forms

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Effects of ozone and particulate matter on airway epithelial barrier structure and function: a review of in vitro and in vivo studies

Inhalation Toxicology ◽

10.1080/08958378.2021.1956021 ◽

2021 ◽

pp. 1-16

Author(s):

Timothy Smyth ◽

Steve N. Georas

Keyword(s):

Particulate Matter ◽

Structure And Function ◽

In Vivo Studies ◽

Epithelial Barrier ◽

Airway Epithelial ◽

Barrier Structure ◽

And Function

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Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: In vitro and in vivo studies

International Journal of Molecular Medicine ◽

10.3892/ijmm_00000330 ◽

2009 ◽

Vol 25 (2) ◽

Cited By ~ 3

Author(s):

De Carlo

Keyword(s):

In Vivo Studies ◽

Acellular Matrix ◽

And Function ◽

Islet Survival

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Single-cell transcriptomics reveals multiple neuronal cell types in human midbrain-specific organoids

10.1101/589598 ◽

2019 ◽

Cited By ~ 2

Author(s):

Lisa M. Smits ◽

Stefano Magni ◽

Kamil Grzyb ◽

Paul MA. Antony ◽

Rejko Krüger ◽

...

Keyword(s):

Single Cell ◽

Dopaminergic Neurons ◽

Neuronal Cell ◽

Cell Types ◽

Human Stem Cell ◽

Glutamatergic Neurons ◽

And Function ◽

Excellent Tool

AbstractHuman stem cell-derived organoids have great potential for modelling physiological and pathological processes. They recapitulatein vitrothe organisation and function of a respective organ or part of an organ. Human midbrain organoids (hMOs) have been described to contain midbrain-specific dopaminergic neurons that release the neurotransmitter dopamine. However, the human midbrain contains also additional neuronal cell types, which are functionally interacting with each other. Here, we analysed hMOs at high-resolution by means of single-cell RNA-sequencing (scRNA-seq), imaging and electrophysiology to unravel cell heterogeneity. Our findings demonstrate that hMOs show essential neuronal functional properties as spontaneous electrophysiological activity of different neuronal subtypes, including dopaminergic, GABAergic, and glutamatergic neurons. Recapitulating thesein vivofeatures makes hMOs an excellent tool forin vitrodisease phenotyping and drug discovery.

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In vitro and in vivo preclinical studies predict REGEN-COV protection against emergence of viral escape in humans

10.1101/2021.03.10.434834 ◽

2021 ◽

Author(s):

Richard Copin ◽

Alina Baum ◽

Elzbieta Wloga ◽

Kristen E. Pascal ◽

Stephanie Giordano ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Therapeutic Option ◽

Viral Escape ◽

Spike Protein ◽

In Vivo Studies ◽

Preclinical Studies ◽

Global Pandemic ◽

Emerging Virus

SummaryMonoclonal antibodies against SARS-CoV-2 are a clinically validated therapeutic option against COVID-19. As rapidly emerging virus mutants are becoming the next major concern in the fight against the global pandemic, it is imperative that these therapeutic treatments provide coverage against circulating variants and do not contribute to development of treatment emergent resistance. To this end, we investigated the sequence diversity of the spike protein and monitored emergence of minor virus variants in SARS-COV-2 isolates found in nature or identified from preclinical in vitro and in vivo studies and in the clinic. This study demonstrates that a combination of noncompeting antibodies not only provides full coverage against currently circulating variants but also protects against emergence of new such variants and their potential seeding into the population in a clinical setting.

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