Clinical Development of Regenerative Medicine Targeted for Intervertebral Disc Disease.
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ABSTRACT:
SUBMITTER: Sakai D
PROVIDER: S-EPMC8878570 | biostudies-literature | 2022 Feb
REPOSITORIES: biostudies-literature
Publications
Clinical Development of Regenerative Medicine Targeted for Intervertebral Disc Disease.
Sakai Daisuke D Schol Jordy J Watanabe Masahiko M
Medicina (Kaunas, Lithuania) 20220210 2
Low back pain is critical health, social, and economic issue in modern societies. This disease is often associated with intervertebral disc degeneration; however, contemporary treatments are unable to target this underlying pathology to alleviate the pain symptoms. Cell therapy offers a promising novel therapeutic that, in theory, should be able to reduce low back pain through mitigating the degenerative disc environment. With the clinical development of cell therapeutics ongoing, this review ai ...[more]
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Project description:The intervertebral disc (IVD) comprises a gelatinous inner core (nucleus pulposus; NP) and concentric rings (annulus fibrosus; AF). The NP, an important structure for shock absorption in the vertebrate spinal motion segment, can be traced back to the notochord in ontogenetic lineage. In vertebrates, the notochord undergoes mucinoid changes, and had been considered vestigial until recently. However, observed correlations between IVD degeneration and back pain in humans have renewed interest in the IVD in biomedical fields. Beyond its mechanical contribution to development, the notochord is also an essential signaling center, which coordinates formation of the neural tube and somites. The pertinent signaling molecules, particularly TGF-? and bone morphogenetic proteins (BMPs), continue to play roles in the adult tissues and have been utilized for tissue regeneration. Genetic factors are major determinants of who will develop IVD degeneration and related back pain, and seem to correlate better with disc degeneration and back pain than do external forces on the spine. In summary, the spinal column is a landmark development in evolution. Genes directing the development of the IVD may also contribute to its maintenance, degeneration, and regeneration. Likewise, structural genes as well as genes responsible for maintenance of the structure are related to IVD degeneration. Finally, genes responsible for inflammation may play a dual role in exacerbating degeneration or facilitating repair responses depending on the context.
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Project description:ObjectivePossible regenerative treatments for lumbar intervertebral disc degeneration (DD) are rapidly emerging. There is consensus that the patient that would benefit most has early-stage DD, with a predicted deterioration in the near future. To identify this patient, the aim of this study was to identify prognostic factors for progression of DD.Study designSystematic review.MethodsA systematic search was performed on studies evaluating one or more prognostic factor(s) in the progression of DD. The criteria for inclusion were (a) patients diagnosed with DD on MRI, (b) progression of DD at follow-up, and (c) reporting of one or more prognostic factor(s) in progression of DD. Two authors independently assessed the methodological quality of the included studies. Due to heterogeneity in DD determinants and outcomes, only a best-evidence synthesis could be conducted.ResultsThe search generated 3165 references, of which 16 studies met our inclusion criteria, involving 2.423 patients. Within these, a total of 23 clinical and environmental and 12 imaging factors were identified. There was strong evidence that disc herniation at baseline is associated with progression of DD at follow-up. There is limited evidence that IL6 rs1800795 genotype G/C male was associated with no progression of DD. Some clinical or environmental factors such as BMI, occupation and smoking were not associated with progression.ConclusionsDisc herniation is strongly associated with the progression of DD. Surprisingly, there was strong evidence that smoking, occupation, and several other factors were not associated with the progression of DD. Only one genetic variant may have a protective effect on progression, otherwise there was conflicting or only limited evidence for most prognostic factors. Future research into these prognostic factors with conflicting and limited evidence is not only needed to determine which patients should be targeted by regenerative therapies, but will also contribute to spinal phenotyping.
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