scholarly journals Transplantation of Neural Precursors Derived from Induced Pluripotent Cells Preserve Perineuronal Nets and Stimulate Neural Plasticity in ALS Rats

2020 ◽  
Vol 21 (24) ◽  
pp. 9593
Author(s):  
Serhiy Forostyak ◽  
Oksana Forostyak ◽  
Jessica C. F. Kwok ◽  
Nataliya Romanyuk ◽  
Monika Rehorova ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Perineuronal Nets ◽  
Pluripotent Cells ◽  
Neuronal Phenotype ◽  
Induced Pluripotent Cells ◽  
Genes Expression ◽  
The Central Nervous System ◽  
Induced Pluripotent ◽  
Lateral Sclerosis

A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) treatment is stem cell therapy. Neural progenitors derived from induced pluripotent cells (NP-iPS) might rescue or replace dying motoneurons (MNs). However, the mechanisms responsible for the beneficial effect are not fully understood. The aim here was to investigate the mechanism by studying the effect of intraspinally injected NP-iPS into asymptomatic and early symptomatic superoxide dismutase (SOD)1G93A transgenic rats. Prior to transplantation, NP-iPS were characterized in vitro for their ability to differentiate into a neuronal phenotype. Motor functions were tested in all animals, and the tissue was analyzed by immunohistochemistry, qPCR, and Western blot. NP-iPS transplantation significantly preserved MNs, slowed disease progression, and extended the survival of all treated animals. The dysregulation of spinal chondroitin sulfate proteoglycans was observed in SOD1G93A rats at the terminal stage. NP-iPS application led to normalized host genes expression (versican, has-1, tenascin-R, ngf, igf-1, bdnf, bax, bcl-2, and casp-3) and the protection of perineuronal nets around the preserved MNs. In the host spinal cord, transplanted cells remained as progenitors, many in contact with MNs, but they did not differentiate. The findings suggest that NP-iPS demonstrate neuroprotective properties by regulating local gene expression and regulate plasticity by modulating the central nervous system (CNS) extracellular matrix such as perineuronal nets (PNNs).

scholarly journals Neuron-Glia Interactions in Neural Plasticity: Contributions of Neural Extracellular Matrix and Perineuronal Nets

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Egor Dzyubenko ◽  
Christine Gottschling ◽  
Andreas Faissner
Keyword(s):  
Extracellular Matrix ◽  
Neural Plasticity ◽  
Signal Transmission ◽  
Perineuronal Nets ◽  
Molecular Scaffold ◽  
Macromolecular Assemblies ◽  
Neuropsychiatric Diseases ◽  
The Central Nervous System ◽  
And Function

Synapses are specialized structures that mediate rapid and efficient signal transmission between neurons and are surrounded by glial cells. Astrocytes develop an intimate association with synapses in the central nervous system (CNS) and contribute to the regulation of ion and neurotransmitter concentrations. Together with neurons, they shape intercellular space to provide a stable milieu for neuronal activity. Extracellular matrix (ECM) components are synthesized by both neurons and astrocytes and play an important role in the formation, maintenance, and function of synapses in the CNS. The components of the ECM have been detected near glial processes, which abut onto the CNS synaptic unit, where they are part of the specialized macromolecular assemblies, termed perineuronal nets (PNNs). PNNs have originally been discovered by Golgi and represent a molecular scaffold deposited in the interface between the astrocyte and subsets of neurons in the vicinity of the synapse. Recent reports strongly suggest that PNNs are tightly involved in the regulation of synaptic plasticity. Moreover, several studies have implicated PNNs and the neural ECM in neuropsychiatric diseases. Here, we highlight current concepts relating to neural ECM and PNNs and describe anin vitroapproach that allows for the investigation of ECM functions for synaptogenesis.

scholarly journals Obtaining Consent for Future Research with Induced Pluripotent Cells: Opportunities and Challenges

PLoS Biology ◽  
2009 ◽  
Vol 7 (2) ◽  
pp. e1000042 ◽  
Author(s):  
Katriina Aalto-Setälä ◽  
Bruce R Conklin ◽  
Bernard Lo
Keyword(s):  
Future Research ◽  
Pluripotent Cells ◽  
Induced Pluripotent Cells ◽  
Induced Pluripotent

Overview of existing in vitro BBB models: advantages and disadvantages, current state and future prospects

2021 ◽  
Vol 10 (3) ◽  
pp. 109-120
Author(s):  
A. I. Mosiagina ◽  
A. V. Morgun ◽  
A. B. Salmina
Keyword(s):  
Neurovascular Unit ◽  
Clinical Trial Data ◽  
Advantages And Disadvantages ◽  
The Central Nervous System ◽  
Complex Relationships ◽  
On Chip ◽  
Induced Pluripotent ◽  
Level Of Understanding

There is growing research focusing on endothelial cells as separate units of the blood-brain barrier (BBB), and on the complex relationships between different types of cells within a neurovascular unit. To conduct this type of studies, researches use vastly different in vitro BBB models. The main objective of such models is to study the BBB permeability for different molecules, and to advance the current level of understanding the mechanisms of disease and to develop methods of targeted therapy for the central nervous system. The analysis of the existing Abstract in vitro BBB models and their advantages/disadvantages was conducted using the clinical trial data obtained in Russian/foreign countries. In this review, the authors highlight the most relevant assessment parameters and propose a unified classification of in vitro BBB models. According to the performed analysis, there is a tendency to move from 2D BBB models based on semipermeable inserts to 3D BBB spheroid and microfluidic organ-on-chip models. Moreover, the use of human induced pluripotent stem cells instead of animal primary cells will make it possible to reliably scale the results obtained in vitro to conditions in vivo.

scholarly journals Questioned validity of Gene Expression Dysregulated Domains in Down's Syndrome

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 269 ◽  
Author(s):  
Long H. Do ◽  
William C. Mobley ◽  
Nishant Singhal
Keyword(s):  
Gene Expression ◽  
Monozygotic Twins ◽  
Recent Analysis ◽  
Ts65dn Mouse ◽  
Pluripotent Cells ◽  
Induced Pluripotent Cells ◽  
Independent Analysis ◽  
Human Ipscs ◽  
Rnaseq Data ◽  
Induced Pluripotent

Recently, in studies examining fibroblasts obtained from the tissues of one set of monozygotic twins (i.e. fetuses derived from the same egg) discordant for trisomy 21 (Down syndrome; DS), Letourneau et al., reported the presence of a defined pattern of dysregulation within specific genomic domains they referred to as Gene Expression Dysregulated Domains (GEDDs). GEDDs were described as alternating segments of increased or decreased gene expression affecting all chromosomes. Strikingly, GEDDs in fibroblasts were largely conserved in induced pluripotent cells (iPSCs) generated from the twin’s fibroblasts as well as in fibroblasts from the Ts65Dn mouse model of DS. Our recent analysis failed to find GEDDs. We reexamined the human iPSCs RNAseq data from Letourneau et al., and data from this same research group published earlier examining iPSCs from the same monozygotic twins. An independent analysis of RNAseq data from Ts65Dn fibroblasts also failed to confirm presence of GEDDs. Our analysis questions the validity of GEDDs in DS.

scholarly journals Genetic Correction of Sickle Cell Anemia and β-Thalassemia: Progress and New Perspective

2010 ◽  
Vol 10 ◽  
pp. 644-654 ◽  
Author(s):  
Ajay Perumbeti ◽  
Punam Malik
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Globin Genes ◽  
Induced Pluripotent Cells ◽  
Substantial Progress ◽  
Lentivirus Vectors ◽  
New Perspective ◽  
Induced Pluripotent ◽  
New Strategies

Gene therapy for β-globinopathies, particularly β-thalassemia and sickle cell anemia, holds promise for the future as a definitive corrective approach for these common and debilitating disorders. Correction of the β-globinopathies using lentivirus vectors carrying the β- or γ-globin genes and elements of the locus control region has now been well established in murine models, and an understanding of "what is required to cure these diseases" has been developed in the first decade of the 21st century. A clinical trial using one such vector has been initiated in France with intriguing results, while other trials are under development. Vector improvements to enhance the safety and efficiency of lentivirus vectors are being explored, while new strategies, including homologous recombination in induced pluripotent cells, for correction of sickle cell anemia have shown proof-of-conceptin vitro. Here, a review is provided of the current substantial progress in genetic correction of β-globin disorders.

scholarly journals A defined culture method enabling the establishment of ring sideroblasts from induced pluripotent cells of X-linked sideroblastic anemia

Haematologica ◽  
2018 ◽  
Vol 103 (5) ◽  
pp. e188-e191 ◽  
Author(s):  
Shunsuke Hatta ◽  
Tohru Fujiwara ◽  
Takako Yamamoto ◽  
Kei Saito ◽  
Mayumi Kamata ◽  
...  
Keyword(s):  
Culture Method ◽  
Pluripotent Cells ◽  
Sideroblastic Anemia ◽  
Induced Pluripotent Cells ◽  
Ring Sideroblasts ◽  
Induced Pluripotent ◽  
Defined Culture

GENERATION OF RABBIT PLURIPOTENT STEM CELL LINES

2012 ◽  
Vol 24 (1) ◽  
pp. 286
Author(s):  
A. Dinnyes ◽  
M. K. Pirity ◽  
E. Gocza ◽  
P. Osteil ◽  
N. Daniel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Pluripotent Stem Cells ◽  
Pluripotent Stem Cell ◽  
Pluripotent Cells ◽  
Domestic Species ◽  
Isolation And Characterization ◽  
Induced Pluripotent ◽  
Pluripotency Genes

Pluripotent stem cells have the capacity to divide indefinitely and to differentiate to all the somatic tissues. They can be genetically manipulated in vitro by knocking in and out genes, therefore they serve as an excellent tool for gene-function studies and for the generation of models for human diseases. Since 1981, when the first mouse embryonic stem cell (ESC) line was generated, several attempts have been made to generate pluripotent stem cells from other species as it would help us to understand the differences and similarities of signaling pathways involved in pluripotency and differentiation, and would reveal whether the fundamental mechanism controlling self-renewal of pluripotent cells is conserved among different species. This review gives an overlook of embryonic and induced pluripotent stem cell (iPSCs) research in the rabbit which is one of the most relevant non-rodent species for animal models. To date, several lines of putative ESCs and iPSCs have been described in the rabbit. All expressed stem cell-associated markers and exhibited longevity and pluripotency in vitro, but none have been proven to exhibit full pluripotency in vivo. Moreover, similarly to several domestic species, markers used to characterize the putative ESCs are not fully adequate because studies in domestic species have revealed that they are not specific to the pluripotent inner cell mass. Future validation of rabbit pluripotent stem cells would benefit greatly from a reliable panel of molecular markers specific to pluripotent cells of the developing rabbit embryo. The status of isolation and characterization of the putative pluripotency genes in rabbit will be discussed. Using rabbit specific pluripotency genes we might be able to reprogram somatic cells and generate induced pluripotent stem cells more efficiently thus overcome some of the challenges towards harnessing the potential of this technology. This study was financed by EU FP7 (PartnErS, PIAP-GA-2008-218205; InduHeart, PEOPLE-IRG-2008-234390; InduVir, PEOPLE-IRG-2009-245808; RabPstem, PERG07-GA-2010-268422; PluriSys, HEALTH-2007-B-223485; AniStem, PIAP-GA-2011-286264), NKTH-OTKA-EU-7KP HUMAN-MB08-C-80-205; Plurabbit, OMFB-00130-00131/2010 ANR-NKTH/09-GENM-010-01.

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