Emerging Technologies for Molecular Therapy for Intervertebral Disk Degeneration

Bae, Won C.; Masuda, Koichi

doi:10.1016/j.ocl.2011.07.004

Cited by 42 publications

(34 citation statements)

References 121 publications

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“…The morphology of the CEP at ultrashort TE MR imaging may also be related to its transport properties, which can be determined indirectly by using conventional contrast material-enhanced T1-weighted MR imaging (37). Such studies may have implications in the prognosis of disk degeneration or the selection of patients suitable for biologic disk treatments (38), which require proper nutrition to be effective. Although many hurdles remain for in vivo use, with additional studies, ultrashort TE MR imaging of the CEP has the potential to be an additional technique to complement conventional MR evaluation of the intervertebral disks.…”

Section: Discussionmentioning

confidence: 99%

Morphology of the Cartilaginous Endplates in Human Intervertebral Disks with Ultrashort Echo Time MR Imaging

Bae¹,

Statum²,

Zhang³

et al. 2013

Radiology

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Purpose:To image human disk-bone specimens by using conventional spin-echo (SE) and ultrashort echo time (TE) techniques, to describe the morphology at magnetic resonance (MR) imaging, and to identify tissue components contributing to high signal intensity near the cartilaginous endplates (CEPs). Materials and Methods:This study was exempt from institutional review board approval, and informed consent was not required. Five cadaveric lumbar spines (mean age, 61 years 6 11) were prepared into six sample types containing different combinations of disk, uncalcified CEP, calcified CEP, and subchondral bone components and were imaged with proton density-weighted SE (repetition time msec/TE msec, 2000/15) and ultrashort TE (300/0.008, 6.6, echo-subtraction) sequences. Images were evaluated to determine the presence of intermediate-to-high signal intensity in regions excluding the bone marrow. Logistic regression was used to determine which tissue components were significant predictors of the presence of signal intensity for each MR technique. Results:On ultrashort TE MR images, intact disk/uncalcified CEP/ calcified CEP/bone samples exhibited bilaminar intermediate-to-high signal intensity in the region near the CEP, consistent with the histologic appearance of uncalcified and calcified CEPs. Conversely, proton density-weighted SE images exhibited low signal intensity in this region.Results of logistic regression suggested that the presence of uncalcified CEP (P = .023) and calcified CEP (P = .007) in the sample were strong predictors of the presence of signal intensity on ultrashort TE images, whereas the disk was the only predictor (P , .001) of signal intensity on proton density-weighted SE images. Conclusion:Ultrashort TE imaging, unlike proton density-weighted SE imaging, enabled direct visualization of the uncalcified and calcified CEP. Evaluation of the morphology and identification of sources of signal intensity at ultrashort TE MR imaging provides opportunities to potentially aid in the understanding of degenerative disk disease.q RSNA, 2012

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Section: Discussionmentioning

confidence: 99%

Morphology of the Cartilaginous Endplates in Human Intervertebral Disks with Ultrashort Echo Time MR Imaging

Bae¹,

Statum²,

Zhang³

et al. 2013

Radiology

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“…Apart from drug administration, this route is used for investigating nutrient pathways by following the movement of intravenously injected gadolinium in the disc by MRI (Bendsten et al, 2011;Nguyen-minh et al, 1998;Rajasekaran et al, 2004Rajasekaran et al, , 2008. While intradiscal injection of bioactive agents such as growth factors is currently the preferred route for experimental studies of disc repair (Bae and Masuda, 2011;Woods et al, 2011), an increasing number of studies suggests that needle puncture of the annulus may lead to disc degeneration and increases in the risk of herniation and of post injection surgery (Carragee et al, 2009;Michalek et al, 2010). Transport of these agents into the disc via intravenous injection might hence be the only safe route for patient treatment (Kang, 2010).…”

Section: Introductionmentioning

confidence: 99%

Computational pharmacokinetics of solute penetration into human intervertebral discs—Effects of endplate permeability, solute molecular weight and disc size

Motaghinasab

Shirazi-Adl

Urban

et al. 2012

Journal of Biomechanics

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“…57 Promising targets for gene therapy have included LMP-1 (regulation of BMP-7), disintegrin, MMPs, TIMPs, and chondrocyte-specific transcription factors (Ad-Sox9). [58][59][60][61][62][63] In rat models, plasmid DNA was mixed with microbubbles as a delivery system and transfected genes were still expressed up to 24 weeks from treatment in the cultured IVD. In a rabbit model, increased LMP-1 led to increased expression of PG, BMP-2, and BMP-7.…”

Section: Gene-based Therapymentioning

confidence: 99%

“…In a separate rabbit model, increased expression of TIMPs was associated with delayed degeneration and increased expression of Ad-Sox9 which led to retained chondrocytic appearance and normalization of the ECM. 63 …”

Section: Gene-based Therapymentioning

confidence: 99%

Intervertebral Disk Degeneration and Repair

2018

NEUROSURGERY

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Intervertebral disk (IVD) degeneration is a natural progression of the aging process. Degenerative disk disease (DDD) is a pathologic condition associated with IVD that has been associated with chronic back pain. There are a variety of different mechanisms of DDD (genetic, mechanical, exposure). Each of these pathways leads to a final common result of unbalancing the anabolic and catabolic environment of the extracellular matrix in favor of catabolism. Attempts have been made to gain an understanding of the process of IVD degeneration with in Vitro studies. These models help our understanding of the disease process, but are limited as they do not come close to replicating the complexities that exist with an in Vivo model. Animal models have been developed to help us gain further understanding of the degenerative cascade of IVD degeneration In Vivo and test experimental treatment modalities to either prevent or reverse the process of DDD. Many modalities for treatment of DDD have been developed including therapeutic protein injections, stem cell injections, gene therapy, and tissue engineering. These interventions have had promising outcomes in animal models. Several of these modalities have been attempted in human trials, with early outcomes having promising results. Further, increasing our understanding of the degenerative process is essential to the development of new therapeutic interventions and the optimization of existing treatment protocols. Despite limited data, biological therapies are a promising treatment modality for DDD that could impact our future management of low back pain.

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Emerging Technologies for Molecular Therapy for Intervertebral Disk Degeneration

Cited by 42 publications

References 121 publications

Morphology of the Cartilaginous Endplates in Human Intervertebral Disks with Ultrashort Echo Time MR Imaging

Morphology of the Cartilaginous Endplates in Human Intervertebral Disks with Ultrashort Echo Time MR Imaging

Computational pharmacokinetics of solute penetration into human intervertebral discs—Effects of endplate permeability, solute molecular weight and disc size

Intervertebral Disk Degeneration and Repair

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