The spine journal : official journal of the North American Spine Society
-
Review
The effects of microenvironment in mesenchymal stem cell-based regeneration of intervertebral disc.
Recent studies have demonstrated new therapeutic strategy using transplantation of mesenchymal stem cells (MSCs), especially bone marrow-derived MSCs (BM-MSCs), to preserve intervertebral disc (IVD) structure and functions. It is important to understand whether and how the MSCs survive and thrive in the hostile microenvironment of the degenerated IVD. Therefore, this review majorly examines how resident disc cells, hypoxia, low nutrition, acidic pH, mechanical loading, endogenous proteinases, and cytokines regulate the behavior of the exogenous MSCs. ⋯ There has been a dramatic improvement in the understanding of potential MSC-based therapy for IVD regeneration. The use of MSCs for IVD degeneration is still at the stage of preclinical and Phase 1 studies. The effects of the disc microenvironment in MSCs survival and function should be closely studied for transferring MSC transplantation from bench to bedside successfully.
-
Intervertebral disc (IVD) degeneration remains a clinically important condition for which treatment is costly and relatively ineffective. The molecular basis of degenerative disc disease has been an intense focus of research recently, which has greatly increased our understanding of the biology underlying this process. ⋯ A detailed understanding of the biology of IVD degeneration is essential to the design of therapeutic solutions to treat degenerative discs. Although significant advances have been made in explaining the biologic mediators of disc degeneration, the inhospitable biochemical environment of the IVD remains a challenging environment for biological therapies.
-
The evidence surrounding the topic of adjacent segment degeneration and disease has increased dramatically with an abundant amount of literature discussing the incidence of and techniques to avoid it. However, this evidence is often confusing to discern because of various definitions of both adjacent segment degeneration and disease. ⋯ Adjacent segment disease and degeneration remain a multifactorial problem with several techniques being developed recently to minimize them. In the future, it is likely that the popularity of these techniques will be dependent on the long-term results, which are currently unavailable.
-
Controversies persist for the best treatment of burst fractures of the thoracolumbar spine. Anterior corpectomy and discectomy followed by reconstruction with intervertebral cage and posterior fixation, for example, are based mainly on the widespread assumption that intervertebral discs involved in burst-type fractures, typically, do not survive the traumatic event and will degenerate irrevocably. ⋯ Intervertebral discs adjacent to traumatic burst fractures treated with pedicle screw instrumentation and direct end-plate restoration do not routinely seem to progress to severe degeneration at 12 to 18 months postinjury.
-
Nuclear factor-κB (NF-κB) is an essential gene transcriptional regulator of inflammatory cytokines, and it plays important roles in numerous conditions, including inflammatory and neuropathic pain, especially when discogenic pain is involved. Phosphorylation of IκB protein through IκB kinase (IKK) is the first step in the activation of NF-κB activation and the upregulation of NF-κB-responsive genes. ⋯ The neuropeptide CGRP as a pain marker was upregulated in DRG neurons innervating the injured IVDs, and intradiscal inhibition of IKKβ significantly suppressed CGRP production in the DRG neurons innervating the rat IVD, suggesting the possible analgesic effect of IKKβ inhibition in discogenic pain.