Electric Signals Regulate the Directional Migration of Oligodendrocyte Progenitor Cells (OPCs) via β1 Integrin

Zhu, Bangfu; Nicholls, Matthew; Gu, Yu; Zhang, Gaofeng; Zhao, Chao; Franklin, Robin J.M.; Song, Bing

doi:10.3390/ijms17111948

Cited by 15 publications

(9 citation statements)

References 43 publications

(89 reference statements)

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“…TGF-β1 can induce the expression of integrin β1 and the activation of integrin β1 can enhance the effect of TGF-β1-mediated collagen synthesis (25,26). In a study investigating the central nervous system, oligodendrocyte progenitor cells were exposed to physiological levels of electrical stimulation and were found to display a marked electrotactic response that was dependent on integrin β1 (27). In the present study, it was found that the levels of integrin β1 were lower in the grade II and grade III groups compared to the control group, while the grade III group displayed a more marked reduction than that in the grade II group (Fig.…”

Section: Resultsmentioning

confidence: 99%

Effect of integrin β1 in the treatment of stress urinary incontinence by electrical stimulation

Liu

et al. 2019

Mol Med Report

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The aim of the present study was to investigate the protective effect of integrin β1 in the treatment of stress urinary incontinence (SUI) by electrical stimulation, and the underlying mechanisms by which electrical stimulation regulates the collagen metabolism of female vaginal wall fibroblasts (FVWFs). FVWFs obtained from the vaginal wall tissue of patients with (Ingelman-Sundberg scale; grade II, n=8; grade III, n=10) or without (n=8) SUI during gynecological operations were isolated by enzymatic digestion and subsequently identified by immunocytochemistry. Following this, cultured FVWFs were treated with an inhibitor of integrin β1, recombinant human integrin β1 and electrical stimulation (100 mv/mm, 2 h, 20 Hz), followed by total mRNA and protein extraction. mRNA and protein expression levels of integrin β1, transforming growth factor (TGF)-β1 and collagen (COL) I and III in FVWFs were quantified by reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis respectively. Integrin β1, TGF-β1 and COL I and III expression levels were decreased in patients with SUI compared with healthy controls, and the grade III group had lower levels than the grade II group. Following electrical stimulation treatment, the expression levels of TGF-β1, COL I and III were enhanced in the grade II group, but not in the grade III group. Nevertheless, the inhibitor of integrin β1 reduced the protective effect of electrical stimulation in the grade II group. In addition, electrical stimulation combined with recombinant human integrin β1 could also protect cells from SUI in the grade III group. The present study provides evidence for the increased degradation of the extracellular matrix and integrin β1 in the vaginal wall tissues of patients with SUI, and the protective effect of electrical stimulation against SUI via integrin β1. These results provide a novel mechanism for the treatment of SUI using electrical stimulation.

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Section: Resultsmentioning

confidence: 99%

Effect of integrin β1 in the treatment of stress urinary incontinence by electrical stimulation

Liu

et al. 2019

Mol Med Report

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“…The process of myelinogenesis is also enhanced by the electric activity of neurons providing signals about targets to be enwrapped with myelin sheaths [ 37 , 38 , 39 ]. Interestingly, although strongly influenced by the environmental clues, oligodendrocytes are able to complete their differentiation process both in vitro and in vivo in the absence of neurons to be myelinated [ 40 , 41 ]. This ability of oligodendrocytes to terminally maturate even when maintained as monocultures, enables their use as in vitro models for various applications, like, for instance, testing drugs and neurotoxicants, or disease modelling [ 42 , 43 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

The Differentiation of Rat Oligodendroglial Cells Is Highly Influenced by the Oxygen Tension: In Vitro Model Mimicking Physiologically Normoxic Conditions

Janowska

Ziemka‐Nałęcz

Sypecka

2018

IJMS

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Oligodendrocyte progenitor cells (OPCs) constitute one of the main populations of dividing cells in the central nervous system (CNS). Physiologically, OPCs give rise to mature, myelinating oligodendrocytes and confer trophic support to their neighboring cells within the nervous tissue. OPCs are known to be extremely sensitive to the influence of exogenous clues which might affect their crucial biological processes, like survival, proliferation, differentiation, and the ability to generate a myelin membrane. Alterations in their differentiation influencing their final potential for myelinogenesis are usually the leading cause of CNS dys- and demyelination, contributing to the development of leukodystrophic disorders. The evaluation of the mechanisms that cause oligodendrocytes to malfunction requires detailed studies based on designed in vitro models. Since OPCs readily respond to changes in local homeostasis, it is crucial to establish restricted culture conditions to eliminate the potential stimuli that might influence oligodendrocyte biology. Additionally, the in vitro settings should mimic the physiological conditions to enable the obtained results to be translated to future preclinical studies. Therefore, the aim of our study was to investigate OPC differentiation in physiological normoxia (5% O2) and a restricted in vitro microenvironment. To evaluate the impact of the combined microenvironmental clues derived from other components of the nervous tissue, which are also influenced by the local oxygen concentration, the process of generating OPCs was additionally analyzed in organotypic hippocampal slices. The obtained results show that OPC differentiation, although significantly slowed down, proceeded correctly through its typical stages in the physiologically relevant conditions created in vitro. The established settings were also conducive to efficient cell proliferation, exerting also a neuroprotective effect by promoting the proliferation of neurons. In conclusion, the performed studies show how oxygen tension influences OPC proliferation, differentiation, and their ability to express myelin components, and should be taken into consideration while planning preclinical studies, e.g., to examine neurotoxic compounds or to test neuroprotective strategies.

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“…EF plays an important role in axon guidance, nerve growth, and neurogenesis, and, applied at a physiological magnitude, could serve as a guiding cue for glial cell migration (Borgens 1988). It has been recently shown that EF regulates the directed migration of OPC in a β-1 integrin-dependent fashion (Zhu et al 2016). However, demonstration of its efficacy in large animal models is warranted, as the delivery of a homogenous EF over an extended range could be challenging in larger brains.…”

Section: Electric Field (Ef) Modulation As a Novel Methods For Manipulmentioning

confidence: 99%

Migratory potential of transplanted glial progenitors as critical factor for successful translation of glia replacement therapy: The gap between mice and men

Srivastava

Bulte

Walczak

et al. 2017

Glia

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Neurological disorders are a major threat to public health. Stem cell-based regenerative medicine is now a promising experimental paradigm for its treatment, as shown in pre-clinical animal studies. Initial attempts have been on the replacement of neuronal cells only, but glial progenitors (GPs) are now becoming strong alternative cellular therapeutic candidates to replace oligodendrocytes and astrocytes as knowledge accumulates about their important emerging role in various disease processes. There are many examples of successful therapeutic outcomes for transplanted GPs in small animal models, but clinical translation has proved to be challenging due to the 1,000-fold larger volume of the human brain compared to mice. Human GPs transplanted into the mouse brain migrate extensively and can induce global cell replacement, but a similar extent of migration in the human brain would only allow for local rather than global cell replacement. We review here the mechanisms that govern cell migration, which could potentially be exploited to enhance the migratory properties of GPs through cell engineering pre-transplantation. We furthermore discuss the (dis)advantages of the various cell delivery routes that are available, with particular emphasis on intra-arterial injection as the most suitable route for achieving global cell distribution in the larger brain. Now that therapeutic success has proven to be feasible in small animal models, future efforts will need to be directed to enhance global cell delivery and migration to make bench-to-bedside translation a reality.

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Electric Signals Regulate the Directional Migration of Oligodendrocyte Progenitor Cells (OPCs) via β1 Integrin

Cited by 15 publications

References 43 publications

Effect of integrin β1 in the treatment of stress urinary incontinence by electrical stimulation

Effect of integrin β1 in the treatment of stress urinary incontinence by electrical stimulation

The Differentiation of Rat Oligodendroglial Cells Is Highly Influenced by the Oxygen Tension: In Vitro Model Mimicking Physiologically Normoxic Conditions

Migratory potential of transplanted glial progenitors as critical factor for successful translation of glia replacement therapy: The gap between mice and men

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