Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture

Jin, Jingyu; Tilve, Sharada; Huang, Zhonghai; Zhou, Libing; Geller, Herbert M.

doi:10.4103/1673-5374.226398

Cited by 37 publications

(11 citation statements)

References 36 publications

(1 reference statement)

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“…Degradation of CSPGs using chondriotinase enzyme was sufficient to restore synaptic activity below the lesion site in SCI rats [ 197 ] and promoted functional recovery following SCI [ 198 , 199 ]. Similarly, an increase of CSPG concentration caused a decrease in neurite length in vitro [ 200 ]. Other cell types implicated in glial scarring include pericytes.…”

Section: Current Challengesmentioning

confidence: 99%

Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Ford

Pearlman

Ruan

et al. 2020

Cells

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Neurodegenerative diseases are characterized by irreversible cell damage, loss of neuronal cells and limited regeneration potential of the adult nervous system. Pluripotent stem cells are capable of differentiating into the multitude of cell types that compose the central and peripheral nervous systems and so have become the major focus of cell replacement therapies for the treatment of neurological disorders. Human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC)-derived cells have both been extensively studied as cell therapies in a wide range of neurodegenerative disease models in rodents and non-human primates, including Parkinson’s disease, stroke, epilepsy, spinal cord injury, Alzheimer’s disease, multiple sclerosis and pain. In this review, we discuss the latest progress made with stem cell therapies targeting these pathologies. We also evaluate the challenges in clinical application of human pluripotent stem cell (hPSC)-based therapies including risk of oncogenesis and tumor formation, immune rejection and difficulty in regeneration of the heterogeneous cell types composing the central nervous system.

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Section: Current Challengesmentioning

confidence: 99%

Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Ford

Pearlman

Ruan

et al. 2020

Cells

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“…We also evaluated the functional relevance of optogenetic stimulation during the differentiation of ChR2-NPCs on axonal growth in two inhibitory models—treatment with lysophosphatidic acid (LPA), a potent mitogen that activates the Rho/ROCK pathway and induces growth cone retraction and neurite collapse [ 25 ], or with chondroitin sulfate proteoglycans (CSPGs), which mimic one of the major inhibitory signals mediated by the glial scar [ 26 ]. Representative images of βIII-tubulin immune staining show that ChR2 activation following BL stimulation counteracted the axonal retraction induced either by LPA ( Figure 5 F,G) or soluble CSPGs ( Figure 5 H,I), showing significant axonal regrowth in both assayed models ( Figure 5 J).…”

Section: Resultsmentioning

confidence: 99%

Optogenetic Modulation of Neural Progenitor Cells Improves Neuroregenerative Potential

Giraldo

Palmero-Canton

Martínez-Rojas

et al. 2020

IJMS

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Neural progenitor cell (NPC) transplantation possesses enormous potential for the treatment of disorders and injuries of the central nervous system, including the replacement of lost cells or the repair of host neural circuity after spinal cord injury (SCI). Importantly, cell-based therapies in this context still require improvements such as increased cell survival and host circuit integration, and we propose the implementation of optogenetics as a solution. Blue-light stimulation of NPCs engineered to ectopically express the excitatory light-sensitive protein channelrhodopsin-2 (ChR2-NPCs) prompted an influx of cations and a subsequent increase in proliferation and differentiation into oligodendrocytes and neurons and the polarization of astrocytes from a pro-inflammatory phenotype to a pro-regenerative/anti-inflammatory phenotype. Moreover, neurons derived from blue-light-stimulated ChR2-NPCs exhibited both increased branching and axon length and improved axon growth in the presence of axonal inhibitory drugs such as lysophosphatidic acid or chondroitin sulfate proteoglycan. Our results highlight the enormous potential of optogenetically stimulated NPCs as a means to increase neuroregeneration and improve cell therapy outcomes for enhancing better engraftments and cell identity upon transplantation in conditions such as SCI.

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“…A number of higher expressed proteins are known to be induced by viral infection or interferon signaling ( FRIL1 FRIH, VCAM1 and PSME1) (Mulvey et al, 1996; Calabresi et al, 2001). In addition, a number of extracellular matrix and cell adhesion proteins ( CSPG5, NCHL1, CTNA1 and NFASC ) were lower expressed (Hillenbrand et al, 1999; Drees et al, 2005; Liu et al, 2011; Jin et al, 2018) (Table 4). PANTHER analysis of this list of 84 proteins yielded no significant associations with any known GO or Pathways identifiers.…”

Section: Resultsmentioning

confidence: 99%

The Effects of Sindbis Viral Vectors on Neuronal Function

Uyaniker

Spek

Reinders

et al. 2019

Front. Cell. Neurosci.

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Viral vectors are attractive tools to express genes in neurons. Transduction of neurons with a recombinant, replication-deficient Sindbis viral vector is a method of choice for studying the effects of short-term protein overexpression on neuronal function. However, to which extent Sindbis by itself may affect neurons is not fully understood. We assessed effects of neuronal transduction with a Sindbis viral vector on the transcriptome and proteome in organotypic hippocampal slice cultures, and analyzed the electrophysiological properties of individual CA1 neurons, at 24 h and 72 h after viral vector injection. Whereas Sindbis caused substantial gene expression alterations, changes at the protein level were less pronounced. Alterations in transcriptome and proteome were predominantly limited to proteins involved in mediating anti-viral innate immune responses. Sindbis transduction did not affect the intrinsic electrophysiological properties of individual neurons: the membrane potential and neuronal excitability were similar between transduced and non-transduced CA1 neurons up to 72 h after Sindbis injection. Synaptic currents also remained unchanged upon Sindbis transduction, unless slices were massively infected for 72 h. We conclude that Sindbis viral vectors at low transduction rates are suitable for studying short-term effects of a protein of interest on electrophysiological properties of neurons, but not for studies on the regulation of gene expression.

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Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture

Cited by 37 publications

References 36 publications

Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges

Optogenetic Modulation of Neural Progenitor Cells Improves Neuroregenerative Potential

The Effects of Sindbis Viral Vectors on Neuronal Function

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