scholarly journals Charged Modification of Hydrogel for Nerve Regeneration

2008 ◽  
Vol 2 (2) ◽  
Author(s):  
Mahrokh Dadsetan ◽  
Andrew M. Knight ◽  
Catalina Vallejo ◽  
Lichun Lu ◽  
Anthony J. Windebank ◽  
...  
Keyword(s):  
Charge Density ◽  
Neurite Outgrowth ◽  
Nerve Regeneration ◽  
Cell Attachment ◽  
Hydrolytic Degradation ◽  
Oxidative Degradation ◽  
Electrical Charge ◽  
Swelling Ratio ◽  
Positively Charged

Natural and synthetic hydrogels have attracted much attention for nerve regeneration. Previous studies have shown that electrical charge has significant effect on stimulation of neurite outgrowth. In this work, incorporation of a positively charged monomer into the photocrosslinkable oligo(polyethylene glycol) fumarate (OPF) hydrogel has been investigated. We have evaluated the effect of localized positive charge on neurite outgrowth in culture with an objective that positively charged hydrogels ultimately can be used for stimulating in vivo nerve regeneration. The effect of charged modification has been also studied on mechanical properties and swelling ratio of these hydrogels. Our data indicated that with increasing charge density hydrogels swelling ratio increased in water, however it remained constant in PBS. We also demonstrated that compressive modulus and tensile strength of the hydrogels improved with incorporation of electrical charge into the hydrogels. Biodegradation of modified hydrogels was investigated in a series of biomimetic solutions. OPF hydrogels appeared to be more susceptible to oxidative degradation as opposed to the hydrolytic degradation in enzymes and acidic solution, and the degradation rate was correlated to the PEG molecular weight and charge density of the hydrogels. To investigate the effect of charge modification on nerve cell attachment and differentiation, dissociated dorsal root ganglion (DRG) cells were plated onto the modified and unmodified hydrogels surfaces. DRG cells attached and extended their neurites more readily on the surface of positively charged hydrogels as opposed to the unmodified hydrogels.

DPSCs seeded in acellular nerve grafts processed by Myroilysin improve nerve regeneration

2018 ◽  
Vol 33 (6) ◽  
pp. 819-833 ◽  
Author(s):  
Wenlan Qiao ◽  
Lu Lu ◽  
Guangxue Wu ◽  
Xianglian An ◽  
Dong Li ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Cell Attachment ◽  
Longitudinal Axis ◽  
Nerve Graft ◽  
Nerve Grafts ◽  
Nerve Conduits ◽  
Rejection Response ◽  
Host Rejection

Since synthetic nerve conduits do not exhibit ideal regeneration characteristics, they are generally inadequate substitutes for autologous nerve grafts in the repair of long peripheral nerve defects. To resolve this problem, in this study, a nerve regeneration acellular nerve graft (ANG) with homologous dental pulp stem cells (DPSCs) was constructed. Xenogeneic ANG was processed by Myroilysin to completely remove cells and myelin sheath, while preserving extracellular matrix (ECM) microstructure of the natural nerve. The study revealed that ANG could support cell attachment and proliferation and did not stimulate a vigorous host rejection response. After inoculation of rabbit DPSCs (r-DPSCs) onto ANG, cells were observed to align along the longitudinal axis of the acellular nerve matrix (ANM) and persistently express NGF and BDNF. Undifferentiated r-DPSCs also presented glial cell characteristics and promoted nerve regeneration after transplantation in vivo. We repaired 1 cm purebred New Zealand White Rabbits sciatic nerve defects using this nerve graft construction, and nerve gap regeneration was indicated by electrophysiological and histological analysis. Therefore, we conclude that the combination of an ANG processed by Myroilysin with DPSCs providing a microenvironment that increases nerve regeneration for repairing peripheral nerve defects.

INVESTIGATING CRMP4 FUNCTION IN NERVE REGENERATION

2008 ◽  
Vol 31 (4) ◽  
pp. 18
Author(s):  
S Ong Tone ◽  
Y Z Alabed ◽  
A Di Polo ◽  
A E Fournier
Keyword(s):  
Optic Nerve ◽  
Neurite Outgrowth ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Molecular Mechanisms ◽  
Ganglion Cells ◽  
Cell Types ◽  
Therapeutic Interventions ◽  
Growth State

Background: The failure of CNS neurons to spontaneously regenerate following injury can be partially attributed to the expression of neurite outgrowth inhibitory myelin associated inhibitors (MAIs). MAIs signal through a tripartite receptor complex to activate the cytosolic protein RhoA and influence cytoskeletal dynamics. RhoA antagonists promote neuronal survival and regeneration in animal models of nerve injury. However, RhoA's potential as a therapeutic target may be limited by its widespread roles in multiple cellular processes and cell types. In an attempt to discover more specific therapeutic targets to promote nerve regeneration, our lab identified the cytosolic phosphoprotein CRMP4b (Collapsin Response Mediator Protein 4b) as a protein that functionally interacts with RhoA to mediate neurite outgrowth inhibition. Blockade of the RhoA-CRMP4b interaction with a competitive peptide (C4RIP) attenuates myelin-dependent neurite outgrowth inhibition. Methods: We are currently investigating the in vivo roles of CRMP4in regeneration in an optic nerve injury model by developing a readily deliverable version of C4RIP. Results: Preliminary results suggest that overexpression of C4RIP in retinal ganglion cells by adeno-associated virus does not promote regeneration. However, studies investigating the ability of C4RIP to promote nerve regeneration into the optic nerve following stimulation of neurons into anactive growth state are currently in progress. Conclusion: Elucidating the role of CRMP4 in nerve regeneration may provide insight into the molecular mechanisms following nervous system injury and lead to the development of more specific therapeutic interventions. Reference: Alabed YZ, Pool M, Ong Tone S, Fournier AE.Identification of CRMP4 as a convergent regulator of axon outgrowth inhibition. J Neurosci 2007;27:1702-11.

The role of CRMP4 in nerve regenerations

2007 ◽  
Vol 30 (4) ◽  
pp. 91
Author(s):  
Stephan Ong Tone ◽  
Yazan Z. Alabed ◽  
Alyson E. Fournier
Keyword(s):  
Neurite Outgrowth ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Molecular Mechanisms ◽  
Time Lapse ◽  
Functional Connections ◽  
Cord Injury ◽  
Cns Neurons

The inability of CNS neurons to regenerate and reform functional connections following spinal cord injury has devastating clinical consequences. The failure of CNS neurons to spontaneously regenerate following injury can be partially attributed to the expression of neurite outgrowth inhibitory myelin associated inhibitors (MAIs). MAIs signal through a tripartite receptor complex to activate the cytosolic protein RhoA and influence cytoskeletal dynamics. RhoA antagonists promote neuronal survival and regeneration in animal models of nerve injury. However, RhoA's potential as a therapeutic target may be limited by its widespread roles in multiples cellular processes and cell types. In an attempt to discover more specific therapeutic targets to promote nerve regeneration, our lab identified the cytosolic phosphoprotein CRMP4b (Collapsin Response Mediator Protein 4b) as a protein that functionally interacts with RhoA to mediate neurite outgrowth inhibition. siRNA-mediated knockdown of CRMP4 and blockade of the RhoA-CRMP4b interaction with a competitive peptide (C4RIP) attenuates myelin-dependent neurite outgrowth inhibition. Analysis of the proximal tip of extending axons (growth cones) by time lapse video microscopy reveals that C4RIP regulates filopodial dynamics indicating that C4RIP modulates the actin cytoskeleton. We are currently investigating the in vivo roles of CRMP4 in regeneration in an optic nerve injury model by developing readily deliverable C4RIP and a CRMP4 knockout mouse. Elucidating the role of CRMP4 in nerve regeneration may provide insight into the molecular mechanisms following nervous system injury.

scholarly journals Transformation-associated alterations in interactions between pre-B cells and fibronectin

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2311-2320 ◽  
Author(s):  
FM Lemoine ◽  
S Dedhar ◽  
GM Lima ◽  
CJ Eaves
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Cell Attachment ◽  
Attachment Site ◽  
Receptor Antibodies

Abstract Marrow stromal elements produce as yet uncharacterized soluble growth factors that can stimulate the proliferation of murine pre-B cells, although close contact between these two cell types appears to ensure a better pre-B cell response. We have now shown that freshly isolated normal pre-B cells (ie, the B220+, surface mu- fraction of adult mouse bone marrow) adhere to fibronectin (FN) via an RGD cell-attachment site, as shown in a serum-free adherence assay, and they lose this functional ability on differentiation in vivo into B cells (ie, the B220+, surface mu+ fraction). Similarly, cells from an immortalized but stromal cell-dependent and nontumorigenic murine pre-B cell line originally derived from a Whitlock-Witte culture were also found to adhere to fibronectin (FN) via an RGD cell-attachment site. Moreover, in the presence of anti-FN receptor antibodies, the ability of this immortalized pre-B cell line to proliferate when co-cultured with a supportive stromal cell line (M2–10B4 cells) was markedly reduced (down to 30% of control). This suggests that pre-B cell attachment to FN on stromal cells may be an important component of the mechanism by which stromal cells stimulate normal pre-B cell proliferation and one that is no longer operative to control their more differentiated progeny. Two differently transformed pre-B cell lines, both of which are autocrine, stromal-independent, tumorigenic in vivo, and partially or completely differentiation-arrested at a very early stage of pre-B cell development, did not bind to FN. In addition, anti-FN receptor antibodies were much less effective in diminishing the ability of these tumorigenic pre-B cells to respond to M2–10B4 cell stimulation, which could still be demonstrated when the tumorigenic pre-B cells were co- cultured with M2–10B4 cells at a sufficiently low cell density. Analysis of cell surface molecules immunoprecipitated from both the nontumorigenic and tumorigenic pre-B cell lines by an anti-FN receptor antibody showed an increase in very late antigen (VLA) alpha chain(s) in both tumorigenic pre-B cell lines and a decrease in the beta 1 chain in one. Interestingly, all of the pre-B cell lines expressed similar amounts of messenger RNA for the beta 1 chain of the FN receptor. These results suggest that alteration of FN receptor expression on pre-B cells may represent a mechanism contributing to the outgrowth of leukemic pre-B cells with an autocrine phenotype and capable of stromal cell-independent, autonomous growth.

scholarly journals Myelin basic protein enhances axonal regeneration from neural progenitor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhengjian Yan ◽  
Lei Chu ◽  
Xiaojiong Jia ◽  
Lu Lin ◽  
Si Cheng
Keyword(s):  
Myelin Basic Protein ◽  
Neurite Outgrowth ◽  
Progenitor Cells ◽  
Axonal Regeneration ◽  
Neural Progenitor Cells ◽  
Basic Protein ◽  
Neural Progenitor ◽  
Dependent Manner ◽  
Cord Injury

Abstract Introduction Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs. Methods We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo. Results Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp’s stimulatory effects on NPC neurite outgrowth are mediated by Mbp’s production of L1-70. Furthermore, we determined that Mbp/L1-70’s stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice. Conclusions We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.

scholarly journals Newly Emerging Airborne Pollutants: Current Knowledge of Health Impact of Micro and Nanoplastics

2021 ◽  
Vol 18 (6) ◽  
pp. 2997
Author(s):  
Alessio Facciolà ◽  
Giuseppa Visalli ◽  
Marianna Pruiti Ciarello ◽  
Angela Di Pietro
Keyword(s):  
Surface Area ◽  
Current Knowledge ◽  
Oxidative Degradation ◽  
Health Impact ◽  
Outdoor Exposure ◽  
Environmental Matrices ◽  
Potential Health ◽  
Bodily Fluids

Plastics are ubiquitous persistent pollutants, forming the most representative material of the Anthropocene. In the environment, they undergo wear and tear (i.e., mechanical fragmentation, and slow photo and thermo-oxidative degradation) forming secondary microplastics (MPs). Further fragmentation of primary and secondary MPs results in nanoplastics (NPs). To assess potential health damage due to human exposure to airborne MPs and NPs, we summarize the evidence collected to date that, however, has almost completely focused on monitoring and the effects of airborne MPs. Only in vivo and in vitro studies have assessed the toxicity of NPs, and a standardized method for their analysis in environmental matrices is still missing. The main sources of indoor and outdoor exposure to these pollutants include synthetic textile fibers, rubber tires, upholstery and household furniture, and landfills. Although both MPs and NPs can reach the alveolar surface, the latter can pass into the bloodstream, overcoming the pulmonary epithelial barrier. Despite the low reactivity, the number of surface area atoms per unit mass is high in MPs and NPs, greatly enhancing the surface area for chemical reactions with bodily fluids and tissue in direct contact. This is proven in polyvinyl chloride (PVC) and flock workers, who are prone to persistent inflammatory stimulation, leading to pulmonary fibrosis or even carcinogenesis.

scholarly journals Effects of Size and Surface Properties of Nanodiamonds on the Immunogenicity of Plant-Based H5 Protein of A/H5N1 Virus in Mice

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1597
Author(s):  
Thuong Thi Ho ◽  
Van Thi Pham ◽  
Tra Thi Nguyen ◽  
Vy Thai Trinh ◽  
Tram Vi ◽  
...  
Keyword(s):  
High Pressure ◽  
Neutralizing Antibodies ◽  
H5n1 Virus ◽  
Vaccine Development ◽  
Particle Characterization ◽  
Innovative Strategy ◽  
Specific Igg ◽  
Positively Charged

Nanodiamond (ND) has recently emerged as a potential nanomaterial for nanovaccine development. Here, a plant-based haemagglutinin protein (H5.c2) of A/H5N1 virus was conjugated with detonation NDs (DND) of 3.7 nm in diameter (ND4), and high-pressure and high-temperature (HPHT) oxidative NDs of ~40–70 nm (ND40) and ~100–250 nm (ND100) in diameter. Our results revealed that the surface charge, but not the size of NDs, is crucial to the protein conjugation, as well as the in vitro and in vivo behaviors of H5.c2:ND conjugates. Positively charged ND4 does not effectively form stable conjugates with H5.c2, and has no impact on the immunogenicity of the protein both in vitro and in vivo. In contrast, the negatively oxidized NDs (ND40 and ND100) are excellent protein antigen carriers. When compared to free H5.c2, H5.c2:ND40, and H5.c2:ND100 conjugates are highly immunogenic with hemagglutination titers that are both 16 times higher than that of the free H5.c2 protein. Notably, H5.c2:ND40 and H5.c2:ND100 conjugates induce over 3-folds stronger production of both H5.c2-specific-IgG and neutralizing antibodies against A/H5N1 than free H5.c2 in mice. These findings support the innovative strategy of using negatively oxidized ND particles as novel antigen carriers for vaccine development, while also highlighting the importance of particle characterization before use.

scholarly journals Heat Aged Tensile Strength Retention of Poly (p-phenylene terephthalamide) Sewing Thread

2008 ◽  
Vol 3 (4) ◽  
pp. 155892500800300 ◽  
Author(s):  
Walter R. Hall ◽  
Warren F. Knoff
Keyword(s):  
Hydrolytic Degradation ◽  
Oxidative Degradation ◽  
Thermal Exposure ◽  
Strength Loss ◽  
Degradation Process ◽  
Downstream Processing ◽  
Kink Bands ◽  
Sewing Thread ◽  
Continuous Filament ◽  
Strength Retention

The strength retention after exposure to elevated temperature in air of continuous filament and staple spun PPTA sewing thread and the precursor yarns was determined. For both types, the process of converting the greige yarn to thread reduced the amount of strength retained after thermal exposure. The continuous filament products retained more strength than the staple products. The data was fitted to a kinetic rate model in which two strength loss processes occurred. The first process occurred within about the first 5 minutes of thermal exposure and is hypothesized to be hydrolytic degradation. The estimated secondary degradation process activation energy suggests this to be thermo-oxidative degradation. Optical microscopy of filaments indicates a higher level of kink banding and other damage in continuous filament versus staple products and in finished thread versus the precursor yarns. The kink bands and damage are believed to be caused by the staple manufacturing process and the downstream processing of precursor yarn to finished sewing thread. The kink bands and damage are hypothesized to be responsible for the differences in strength retention.

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