Dataset Information

Microfluidic Disc-on-a-Chip Device for Mouse Intervertebral Disc-Pitching a Next-Generation Research Platform To Study Disc Degeneration.

ABSTRACT: Low back pain is the most common cause of disability worldwide, and intervertebral disc degeneration is a major cause of low back pain. Unfortunately, discogenic low back pain is often treated with symptomatic relief interventions, as no disease-modifying medications are yet available. Both to-be-deciphered disc biology/pathology and inadequate in vitro research platform are major hurdles limiting drug discovery progress for disc degeneration. Here, we developed a microfluidic disc-on-a-chip device tailored for mouse disc organ as an in vitro research platform. We hypothesize that continuous nutrients empowered by a microfluidic device would improve biological performance of cultured mouse discs compared to those in static condition. This device permitted continuous media flow to mimic in vivo disc microenvironment. Intriguingly, mouse discs cultured on the microfluidic device exhibited much higher cell viability, better preserved structure integrity and anabolic-catabolic metabolism in both nucleus pulposus and annulus fibrosus, for up to 21 days compared to those in static culture. This first "disc-on-a-chip" device lays groundwork for future preclinical studies in a relative long-term organ culture given the chronic nature of intervertebral disc degeneration. In addition, this platform is readily transformable into a streamlined in vitro research platform to recapitulate physiological and pathophysiological microenvironment to accelerate disc research.

SUBMITTER: Dai J

PROVIDER: S-EPMC6874371 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Microfluidic Disc-on-a-Chip Device for Mouse Intervertebral Disc-Pitching a Next-Generation Research Platform To Study Disc Degeneration.

Dai Jun J Xing Yuan Y Xiao Li L Li Jingyi J Cao Ruofan R He Yi Y Fang Huang H Periasamy Ammasi A Oberhozler Jose J Jin Li L Landers James P JP Wang Yong Y Li Xudong X

ACS biomaterials science & engineering 20190226 4

Low back pain is the most common cause of disability worldwide, and intervertebral disc degeneration is a major cause of low back pain. Unfortunately, discogenic low back pain is often treated with symptomatic relief interventions, as no disease-modifying medications are yet available. Both to-be-deciphered disc biology/pathology and inadequate in vitro research platform are major hurdles limiting drug discovery progress for disc degeneration. Here, we developed a microfluidic disc-on-a-chip dev ...[more]

PMID: 31763444

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Project description:Background contextDisc degeneration (DD) is a multifaceted chronic process that alters the structure and function of the intervertebral discs and can lead to painful conditions. The pathophysiology of degeneration is not well understood, but previous studies suggest that certain genetic polymorphisms may be important contributing factors leading to an increased risk of DD.PurposeTo review the genetic factors in DD with a focus on polymorphisms and their putative role in the pathophysiology of degeneration. Elucidating the genetic components that are associated with degeneration could provide insights into the mechanism of the process. Furthermore, defining these relationships and eventually using them in a clinical setting may allow an identification and early intervention for those who are at a high risk for painful DD.Study designLiterature review.MethodsThis literature review focused on the studies concerning genetic polymorphisms and their associations with DD.ResultsGenetic polymorphisms in 20 genes have been analyzed in association with DD, including vitamin D receptor, growth differentiation factor 5 (GDF5), aggrecan, collagen Types I, IX, and XI, fibronectin, hyaluronan and proteoglycan link protein 1 (HAPLN1), thrombospondin, cartilage intermediate layer protein (CILP), asporin, MMP1, 2, and 3, parkinson protein 2, E3 ubiquitin protein ligase (PARK2), proteosome subunit ? type 9 (PSMB9), tissue inhibitor of metalloproteinase (TIMP), cyclooxygenase-2 (COX2), and IL1?, IL1?, and IL6. Each genetic polymorphism codes for a protein that has a functional role in the pathogenesis of DD.ConclusionsThere are known associations between several genetic polymorphisms and DD. Of the 20 genes analyzed, polymorphisms in vitamin D receptor, aggrecan, Type IX collagen, asporin, MMP3, IL1, and IL6 show the most promise as functional variants. Genetic studies are crucial for understanding the mechanism of the degeneration. This genetic information could eventually be used as a predictive model for determining a patient's risk for symptomatic DD.

Dataset Information

Microfluidic Disc-on-a-Chip Device for Mouse Intervertebral Disc-Pitching a Next-Generation Research Platform To Study Disc Degeneration.

Publications

Microfluidic Disc-on-a-Chip Device for Mouse Intervertebral Disc-Pitching a Next-Generation Research Platform To Study Disc Degeneration.

Similar Datasets

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