Circular compartmentalized microfluidic platform: Study of axon–glia interactions

Hosmane, Suneil; Yang, In Hong; Ruffin, April; Thakor, Nitish V.; Venkatesan, Arun

doi:10.1039/b918640a

Cited by 76 publications

(69 citation statements)

References 30 publications

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“…1) was fabricated as previously described (23). We previously showed that these devices allow selective growth of axons in one compartment, enable isolation of cell soma from their axons, and allow independent manipulation of somal and axonal compartments (24)(25)(26). To allow cells to adhere to the device, the devices were treated with PDL and Matrigel.…”

Section: Significancementioning

confidence: 99%

In vitro system using human neurons demonstrates that varicella-zoster vaccine virus is impaired for reactivation, but not latency

Sadaoka

Depledge

Rajbhandari

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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104

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Varicella-zoster virus (VZV) establishes latency in human sensory and cranial nerve ganglia during primary infection (varicella), and the virus can reactivate and cause zoster after primary infection. The mechanism of how the virus establishes and maintains latency and how it reactivates is poorly understood, largely due to the lack of robust models. We found that axonal infection of neurons derived from hESCs in a microfluidic device with cell-free parental Oka (POka) VZV resulted in latent infection with inability to detect several viral mRNAs by reverse transcriptase-quantitative PCR, no production of infectious virus, and maintenance of the viral DNA genome in endless configuration, consistent with an episome configuration. With deep sequencing, however, multiple viral mRNAs were detected. Treatment of the latently infected neurons with Ab to NGF resulted in production of infectious virus in about 25% of the latently infected cultures. Axonal infection of neurons with vaccine Oka (VOka) VZV resulted in a latent infection similar to infection with POka; however, in contrast to POka, VOka-infected neurons were markedly impaired for reactivation after treatment with Ab to NGF. In addition, viral transcription was markedly reduced in neurons latently infected with VOka compared with POka. Our in vitro system recapitulates both VZV latency and reactivation in vivo and may be used to study viral vaccines for their ability to establish latency and reactivate. varicella-zoster virus | varicella vaccine | reactivation | latency | herpesvirus V aricella-zoster virus (VZV) is a member of Alphaherpesvirinae, characterized by neurotropism and lifelong latent infection in human dorsal root, cranial nerve, and enteric ganglia (1). During primary infection (varicella), VZV gains access to sensory neurons by two potential routes: retrograde axonal transport from cutaneous lesions or infection of neurons by virus-infected T cells circulating through the body (2). The virus then establishes latency in neurons, and months to years later, when VZV-specific T cells decline, the virus can reactivate to cause herpes zoster.VZV is the only human herpesvirus for which a licensed vaccine is approved, and the live-attenuated vaccine Oka (VOka) virus is effective in preventing both varicella and zoster. VOka was derived from WT parental Oka (POka) by propagation in human embryonic lung cells, guinea pig embryo fibroblasts, and human fibroblasts (3, 4). VOka is a genetic mixture of at least eight genotypes (5), and, initially, the genomes of POka and VOka were found to differ by 42 nucleotides and 20 amino acids (6). A recent study using deep sequencing identified 165 additional nucleotide changes in VOka, although most changes were presence in <10% of viral genomes (7). Attenuation of VOka is postulated to be due to mutations in multiple regions of the genome (8, 9).Despite numerous studies, the mechanisms for establishment and maintenance of VZV latency and subsequent reactivation remain poorly understood, primarily due to the lack of ...

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Section: Significancementioning

confidence: 99%

In vitro system using human neurons demonstrates that varicella-zoster vaccine virus is impaired for reactivation, but not latency

Sadaoka

Depledge

Rajbhandari

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

104

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“…This is an important advantage for separating different cell types in a co-culture [68][69][70] or even separating various parts of a specific cell line or tissue within different microenvironments and subjected to various conditions [71,72]. For example, by using confined geometries, neuronal cell bodies can be restricted to remain at specific regions of the device while their axon can penetrate into other sections [73][74][75][76]. Alternatively, a tissue can be exposed to two or more distinguished physical or biochemical conditions such as different fluid temperatures [77] or multiple biochemical gradients [78,79] formed within microfluidic devices.…”

Section: Developing Novel Microfluidic Devices and Microenvironments mentioning

confidence: 99%

Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering

Shamloo

Mohammadaliha

Mina

2015

Journal of Biotechnology

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“…Interface 11: 20130676 soma or the axon. Hosmane et al [70] created a multiplexed circular version of the platform which used centrifugation to enhance axonal throughput through microchannels, and demonstrated increased microglial accumulation to aid in debris clearance near the site of injured CNS axons seen in figure 5. Peyrin et al [67] developed a three-compartment microfluidic device to study simultaneous axonal degeneration and death mechanisms of CNS axons subjected to axotomy with precise spatio-temporal control.…”

Section: Microfluidic Chemical Injury Devicesmentioning

confidence: 99%

“…Spinning also (f ) enhanced axonal throughput, with no observable enhancement in (g) high-density cultures with all channels occupied by neurites. (h) A PDMS wedge can be used in the axonal compartment to (i) localize microglia (adapted from Hosmane et al [70] with permission from the Royal Society of Chemistry).…”

Section: Microfluidic Physical Injury Devicesmentioning

confidence: 99%

Investigation of nerve injury through microfluidic devices

Siddique

Thakor

2014

J. R. Soc. Interface.

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Traumatic injuries, both in the central nervous system (CNS) and peripheral nervous system (PNS), can potentially lead to irreversible damage resulting in permanent loss of function. Investigating the complex dynamics involved in these processes may elucidate the biological mechanisms of both nerve degeneration and regeneration, and may potentially lead to the development of new therapies for recovery. A scientific overview on the biological foundations of nerve injury is presented. Differences between nerve regeneration in the central and PNS are discussed. Advances in microtechnology over the past several years have led to the development of invaluable tools that now facilitate investigation of neurobiology at the cellular scale. Microfluidic devices are explored as a means to study nerve injury at the necessary simplification of the cellular level, including those devices aimed at both chemical and physical injury, as well as those that recreate the post-injury environment.

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Circular compartmentalized microfluidic platform: Study of axon–glia interactions

Cited by 76 publications

References 30 publications

In vitro system using human neurons demonstrates that varicella-zoster vaccine virus is impaired for reactivation, but not latency

In vitro system using human neurons demonstrates that varicella-zoster vaccine virus is impaired for reactivation, but not latency

Integrative Utilization of Microenvironments, Biomaterials and Computational Techniques for Advanced Tissue Engineering

Investigation of nerve injury through microfluidic devices

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