Exogenous BDNF and Chondroitinase ABC Consisted Biomimetic Microenvironment Regulates Survival, Migration and  Differentiation of Human Neural Progenitor Cells Transplanted into a Rat Auditory Nerve

Kale, Ajay; Novozhilova, Ekaterina; Englund-Johansson, Ulrica; Stupp, Samuel I.; Palmgren, Björn; Olivius, Petri

doi:10.4236/nm.2014.52012

Cited by 3 publications

(4 citation statements)

References 48 publications

(50 reference statements)

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“…Furthermore, astrocytic production of CSPGs has shown to inhibit regeneration both in vitro and in vivo (32)(33)(34). CSPGs are a family of ECM proteins and consist of a protein core to which chondroitin sulphate chains are covalently attached.…”

Section: Myelin-associated Inhibitors Are a Barrier To Repairmentioning

confidence: 99%

“…Adult sensory neurons have been shown to undergo axonal regeneration when transplanted into the corpus callosum provided they are transplanted with minimal trauma to the surrounding tissue (35). Interestingly, when there is increased trauma, or indeed a lesion site, regeneration stops as the axons approach the lesion as there is a high concentration of CSPGs (34).…”

Section: Myelin-associated Inhibitors Are a Barrier To Repairmentioning

confidence: 99%

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518 New In Vitro Model of Traumatic Brain Injury to Assess Biomaterial Based Regenerative Strategies

Basit

Jenkins

Chari

2021

British Journal of Surgery

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Introduction Penetrating traumatic brain injury (pTBI) management is largely supportive, with no clinically established regenerative therapies. Neurocompatible biomaterials offer a high potential to promote regenerative mechanisms but facile, high throughput, pathomimetic in vitro pTBI models for the developmental testing of neuro-materials is lacking. Method A mouse mixed glial culture system was utilised within which penetrating injuries could be induced. DuraGen PlusTM – an FDA approved neurosurgical grade biomaterial could be implanted into lesions to assess cell-biomaterial responses. Reactive gliosis (astrocytic morphological responses/GFAP expression) and microglial infiltration (Iba1 expression) were assessed/quantified. Results Key pathological features of pTBI were observed in the model, with the ability to (i) introduce reproducible lesions (diameter 949 ± 26 μm) and (ii) for DuraGen PlusTM to be implanted into lesions. Peri-lesional astrocytes displayed hypertrophic palisading morphologies and GFAP upregulation, analogous to gliosis in vivo. Significant microglial numbers infiltrated the DuraGen PlusTM implant at 7 days post-lesion (132.41 ± 15.83 cells/mm2) versus lesion only (82.04 ± 5.11 cells/mm2), p < 0.05). Conclusions We have developed a novel, neuropathomimetic pTBI model, wherein biomaterial implantation enables investigation of neural cell-biomaterial responses. This model can facilitate early-stage evaluation of novel biomaterials as high throughput, inexpensive and facile screening tool.

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Section: Myelin-associated Inhibitors Are a Barrier To Repairmentioning

confidence: 99%

Section: Myelin-associated Inhibitors Are a Barrier To Repairmentioning

confidence: 99%

518 New In Vitro Model of Traumatic Brain Injury to Assess Biomaterial Based Regenerative Strategies

Basit

Jenkins

Chari

2021

British Journal of Surgery

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“…We previously reported efficient use of mitogen-expanded human neural progenitor cell (HNPC) lines in neurorestorative studies, in in vitro and in vivo models of the CNS [25]- [30]. These cells respond to physical cues, with increased cell survival and graft-host integration in vivo by using a nanofiber gel as supporting scaffold [31] [32]. Also, chemical cues affect behavior of such cells, as we presented in studies using a co-culture with explanted brain tissue [29], a specific cocktail for dopaminergic neuron differentiation [25], or by different culture media [30].…”

Section: Introductionmentioning

confidence: 99%

Tailor-Made Electrospun Culture Scaffolds Control Human Neural Progenitor Cell Behavior—Studies on Cellular Migration and Phenotypic Differentiation

Englund-Johansson¹,

Netanyah²,

Johansson³

2017

JBNB

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In neuroscience research, cell culture systems are essential experimental platforms. It is of great interest to explore in vivo-like culture substrates. We explored how basic properties of neural cells, nuclei polarization, phenotypic differentiation and distribution/migration, were affected by the culture at poly-L-lactic acid (PLLA) fibrous scaffolds, using a multipotent mitogen-expanded human neural progenitor cell (HNPC) line. HNPCs were seeded, at four different surfaces: two different electrospun PLLA (d = 1.2 -1.3 µm) substrates (parallel or random aligned fibers), and planar PLL-and PLLA surfaces. Nuclei analysis demonstrated a non-directed cellular migration at planar surfaces and random fibers, different from cultures at aligned fibers where HNPCs were oriented parallel with the fibers. At aligned fibers, HNPCs displayed the same capacity for phenotypic differentiation as after culture on the planar surfaces. However, at random fibers, HNPCs showed a significant lower level of phenotypic differentiation compared with cultures at the planar surfaces. A clear trend towards greater neuronal formation at aligned fibers, compared to cultures at random fibers, was noted. We demonstrated that the topography of in vivo-resembling PLLA scaffolds significantly influences HNPC behavior, proven by different migration behavior, phenotypic differentiation potential and nuclei polarization.This knowledge is useful in future exploration of in vivo-resembling neural cell system using electrospun scaffolds.

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“…The generated autoantibodies bind with the AChR binding sites on the ECD, thereby allowing deactivation of AChR, stimulating proliferation of specific T cells, activating the complement system, and leading to MG. We considered inducing animals using a fragment during preparation of the EAMG model. Research has shown that AChRTE (AChR from the TE671 cells of human nerve medulloblastoma) can also react with the human muscular AChR (AChRMU) monoclonal Ab (mAbs) (Gunewardene et al, 2012;Hunt, 2014;Kalel et al, 2014), including mAbs specific to the AChR ECD and MIR regions. It is possible to express AChRMU α subunit ECD protein using AChRTE recombination.…”

Section: Introductionmentioning

confidence: 99%

A new method to induce myasthenia gravis models and the protective effect of soluble decay accelerating factors

et al. 2015

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ABSTRACT. It is expensive to induce experimental autoimmune myasthenia gravis (EAMG) by active immunity, and difficult to obtain natural acetylcholine receptor (AChR). We sought a new method of inducing EAMG by immunizing rats with artificially synthesized AChR. The AChR mRNA in TE671 cells was extracted and reverse transcribed. The inclusion body was purified and protein concentration was determined, and the EAMG animal model was used for induction. The serum was extracted from rat blood. The antibody titer was determined using enzyme-linked immunosorbant assay (ELISA). The concentration of decay accelerating factor (DAF) in the rat serum was determined by ELISA, and the metabolism of serum rDAF was determined by western blot. We evaluated the inhibition of rDAF by determining the 50% complement hemolysis unit in the rat serum. The extracellular domain (ECD) nucleotide sequence clone produced by polymerase chain reaction was completely consistent with that in the human gene bank; it was induced by isopropyl β-D-1-thiogalactopyranoside to express the protein after insertion into vector pET16b. Sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that the inclusion body protein was the exact target. The ECD protein was able to bind with mAb35 after dialysis and renaturation, which demonstrated protein activity. The soluble ECD protein was used to immunize rats and obtain the EAMG models. The inhibitory effect of the complement was unsatisfactory owing to high decay rate after rDAF injection into the EAMG models. It is easy to induce the EAMG model by obtaining the AChRTEα1 subunit ECD protein using the substitution method.

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Exogenous BDNF and Chondroitinase ABC Consisted Biomimetic Microenvironment Regulates Survival, Migration and Differentiation of Human Neural Progenitor Cells Transplanted into a Rat Auditory Nerve

Cited by 3 publications

References 48 publications

518 New In Vitro Model of Traumatic Brain Injury to Assess Biomaterial Based Regenerative Strategies

518 New In Vitro Model of Traumatic Brain Injury to Assess Biomaterial Based Regenerative Strategies

Tailor-Made Electrospun Culture Scaffolds Control Human Neural Progenitor Cell Behavior—Studies on Cellular Migration and Phenotypic Differentiation

A new method to induce myasthenia gravis models and the protective effect of soluble decay accelerating factors

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