Effects of ROCK inhibitor Y27632 and EGFR inhibitor PD168393 on human neural precursors co-cultured with rat auditory brainstem explant

Novozhilova, Ekaterina; Englund-Johansson, Ulrica; Kale, Ajay; Jiao, Yu; Olivius, Petri

doi:10.1016/j.neuroscience.2014.12.009

Cited by 6 publications

(6 citation statements)

References 58 publications

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“…Our results indicate that differences in BMSC migration may be at least partly attributable to the expression of the RhoA/ROCK signaling pathway. This conclusion is further supported by the morphology, projected cell area, and migration area of BMSCs treated with Y27632, a specific inhibitor of ROCKs [34]. We observed increased lamellipodia and filopodia formation by BMSCs in the SEM images of the four types of PET-ALs; immunostaining also revealed increased F-actin staining after the BMSCs were treated with Y27632, and the projected cell areas were significantly increased in the four groups.…”

Section: Discussionsupporting

confidence: 70%

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Effects of Artificial Ligaments with Different Porous Structures on the Migration of BMSCs

Wang

Hou

Yan

et al. 2015

Stem Cells International

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Polyethylene terephthalate- (PET-) based artificial ligaments (PET-ALs) are commonly used in anterior cruciate ligament (ACL) reconstruction surgery. The effects of different porous structures on the migration of bone marrow mesenchymal stem cells (BMSCs) on artificial ligaments and the underlying mechanisms are unclear. In this study, a cell migration model was utilized to observe the migration of BMSCs on PET-ALs with different porous structures. A rabbit extra-articular graft-to-bone healing model was applied to investigate the in vivo effects of four types of PET-ALs, and a mechanical test and histological observation were performed at 4 weeks and 12 weeks. The BMSC migration area of the 5A group was significantly larger than that of the other three groups. The migration of BMSCs in the 5A group was abolished by blocking the RhoA/ROCK signaling pathway with Y27632. The in vivo study demonstrated that implantation of 5A significantly improved osseointegration. Our study explicitly demonstrates that the migration ability of BMSCs can be regulated by varying the porous structures of the artificial ligaments and suggests that this regulation is related to the RhoA/ROCK signaling pathway. Artificial ligaments prepared using a proper knitting method and line density may exhibit improved biocompatibility and clinical performance.

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Section: Discussionsupporting

confidence: 70%

“…Finally, RhoA and ROCK signaling regulate tail retraction and integrin adhesion at the rear of cells [33]. Y27632, a specific inhibitor of ROCKs, inhibits the RhoA kinase family and influences stress fibers, vinculin and myosin light chain phosphatase [34]. …”

Section: Introductionmentioning

confidence: 99%

Effects of Artificial Ligaments with Different Porous Structures on the Migration of BMSCs

Wang

Hou

Yan

et al. 2015

Stem Cells International

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“…Previously, stem cell-derived neural precursors were shown to grow toward a CN slice and make SV2-positive terminals as they reached the CN slice [12, 13]. The current study demonstrates for the first time that hPSC-derived neurites are capable of penetrating growth into the CN slice in vitro (Figures 3 and 4).…”

Section: Discussionsupporting

confidence: 62%

“…These nascent stem cell-derived synapses were immunopositive for the presynaptic markers synapsin I [10, 11] and synaptophysin [7]. Similarly, there are but two published studies describing central auditory reinnervation by human neural precursor cells (derived from a 9-week human embryo [12, 13]) and none describing the use of differentiated hPSC. If the described regenerative studies are to progress toward clinical translation, hPSCs warrant further interrogation in the auditory system.…”

Section: Introductionmentioning

confidence: 99%

Organotypic Cocultures of Human Pluripotent Stem Cell Derived-Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slices

Hyakumura

McDougall

Finch

et al. 2019

Stem Cells International

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Stem cells have been touted as a source of potential replacement neurons for inner ear degeneration for almost two decades now; yet to date, there are few studies describing the use of human pluripotent stem cells (hPSCs) for this purpose. If stem cell therapies are to be used clinically, it is critical to validate the usefulness of hPSC lines in vitro and in vivo. Here, we present the first quantitative evidence that differentiated hPSC-derived neurons that innervate both the inner ear hair cells and cochlear nucleus neurons in coculture, with significantly more new synaptic contacts formed on target cell types. Nascent contacts between stem cells and hair cells were immunopositive for both synapsin I and VGLUT1, closely resembling expression of these puncta in endogenous postnatal auditory neurons and control cocultures. When hPSCs were cocultured with cochlear nucleus brainstem slice, significantly greater numbers of VGLUT1 puncta were observed in comparison to slice alone. New VGLUT1 puncta in cocultures with cochlear nucleus slice were not significantly different in size, only in quantity. This experimentation describes new coculture models for assessing auditory regeneration using well-characterised hPSC-derived neurons and highlights useful methods to quantify the extent of innervation on different cell types in the inner ear and brainstem.

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“…Downstream of EGFR, MAPK signaling mediates CSPG inhibition of neurite growth from cerebellar granule neurons [85]. Blocking EGFR promotes growth and migration of human neural precursor cells [86]. Survival of neural stem cells is promoted by CSPGs acting through EGFR pathways as well as JAK/STAT3 and PI3K/Akt [87].…”

Section: Figurementioning

confidence: 99%

Flexible Roles for Proteoglycan Sulfation and Receptor Signaling

Pearson

Geller

2018

Trends in Neurosciences

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Proteoglycans (PGs) in the extracellular matrix (ECM) play vital roles in axon growth and navigation, plasticity, and regeneration of injured neurons. Different classes of PGs may support or inhibit cell growth, and their functions are determined in part by highly specific structural features. Among these, the pattern of sulfation on the PG sugar chains is a paramount determinant of a diverse and flexible set of outcomes. Recent studies of PG sulfation illustrate the challenges of attributing biological actions to specific sulfation patterns, and suggest ways in which highly similar molecules may exert opposing effects on neurons. The receptors for PGs, which have yet to be fully characterized, display a similarly nuanced spectrum of effects. Different classes of PG function via overlapping families of receptors and signaling pathways. This enables them to control axon growth and guidance with remarkable specificity, but it poses challenges for determining the precise binding interactions and downstream effects of different PGs and their assorted sulfated epitopes. This review examines existing and emerging evidence for the roles of PG sulfation and receptor interactions in determining how these complex molecules influence neuronal development, growth, and function.

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Effects of ROCK inhibitor Y27632 and EGFR inhibitor PD168393 on human neural precursors co-cultured with rat auditory brainstem explant

Cited by 6 publications

References 58 publications

Effects of Artificial Ligaments with Different Porous Structures on the Migration of BMSCs

Effects of Artificial Ligaments with Different Porous Structures on the Migration of BMSCs

Organotypic Cocultures of Human Pluripotent Stem Cell Derived-Neurons with Mammalian Inner Ear Hair Cells and Cochlear Nucleus Slices

Flexible Roles for Proteoglycan Sulfation and Receptor Signaling

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