Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP. We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n = 5) or 4 × 107 cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year. No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI. Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population. ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.

Intervertebral disc (IVD) degeneration can cause chronic lower back pain (LBP), leading to disability. Despite significant advances in the treatment of discogenic LBP, the limitations of current treatments have sparked interest in biological approaches, including growth factor and stem cell injection, as new treatment options for patients with chronic LBP due to IVD degeneration (IVDD). Gene therapy represents exciting new possibilities for IVDD treatment, but treatment is still in its infancy. Literature searches were conducted using PubMed and Google Scholar to provide an overview of the principles and current state of gene therapy for IVDD. Gene transfer to degenerated disc cells in vitro and in animal models is reviewed. In addition, this review describes the use of gene silencing by RNA interference (RNAi) and gene editing by the clustered regularly interspaced short palindromic repeats (CRISPR) system, as well as the mammalian target of rapamycin (mTOR) signaling in vitro and in animal models. Significant technological advances in recent years have opened the door to a new generation of intradiscal gene therapy for the treatment of chronic discogenic LBP.

The development of minimally invasive spinal surgery utilizing navigation and robotics has significantly improved the feasibility, accuracy, and efficiency of this surgery. In particular, these methods provide improved accuracy of pedicle screw placement, reduced radiation exposure, and shortened learning curves for surgeons. However, research on the clinical outcomes and cost-effectiveness of navigation and robot-assisted spinal surgery is still in its infancy. Therefore, there is limited available evidence and this makes it difficult to draw definitive conclusions regarding the long-term benefits of these technologies. In this review article, we provide a summary of the current navigation and robotic spinal surgery systems. We concluded that despite the progress that has been made in recent years, and the clear advantages these methods can provide in terms of clinical outcomes and shortened learning curves, cost-effectiveness remains an issue. Therefore, future studies are required to consider training costs, variable initial expenses, maintenance and service fees, and operating costs of these advanced platforms so that they are feasible for implementation in standard clinical practice.

Currently, the role of transient receptor potential vanilloid type 4 (TRPV4), a nonselective cation channel in the pathology of spinal cord injury (SCI), is not recognized. Herein, we report the expression and contribution of TRPV4 in the pathology of scarring and endothelial and secondary damage after SCI. TRPV4 expression increased during the inflammatory phase in female rats after SCI and was expressed primarily by cells at endothelial-microglial junctions. Two-photon microscopy of intracellular-free Ca²⁺levels revealed a biphasic increase at similar time points after SCI. Expression of TRPV4 at the injury epicenter, but not intracellular-free Ca²⁺, progressively increases with the severity of the injury. Activation of TRPV4 with specific agonist altered the organization of endothelial cells, affected tight junctions in the hCMEC/D3 BBB cell linein vitro, and increases the scarring in rat spinal cord as well as induced endothelial damage. By contrast, suppression of TRPV4 with a specific antagonist or in femaleTrpv4KO mouse attenuated inflammatory cytokines and chemokines, prevented the degradation of tight junction proteins, and preserve blood–spinal cord barrier integrity, thereby attenuate the scarring after SCI. Likewise, secondary damage was reduced, and behavioral outcomes were improved inTrpv4KO mice after SCI. These results suggest that increased TRPV4 expression disrupts endothelial cell organization during the early inflammatory phase of SCI, resulting in tissue damage, vascular destabilization, blood–spinal cord barrier breakdown, and scarring. Thus, TRPV4 inhibition/knockdown represents a promising therapeutic strategy to stabilize/protect endothelial cells, attenuate nociception and secondary damage, and reduce scarring after SCI.SIGNIFICANCE STATEMENTTRPV4, a calcium-permeable nonselective cation channel, is widely expressed in both excitable and nonexcitable cells. Spinal cord injury (SCI) majorly caused by trauma/accidents is associated with changes in osmolarity, mechanical injury, and shear stress. After SCI, TRPV4 was increased and were found to be linked with the severity of injury at the epicenter at the time points that were reported to be critical for repair/treatment. Activation of TRPV4 was damaging to endothelial cells that form the blood–spinal cord barrier and thus contributes to scarring (glial and fibrotic). Importantly, inhibition/knockdown of TRPV4 prevented these effects. Thus, the manipulation of TRPV4 signaling might lead to new therapeutic strategies or combinatorial therapies to protect endothelial cells and enhance repair after SCI.

This study used the finite element method(FEM) to investigate how pressure on the lumbar spine changes during dynamic movements in different postures: standing, erect sitting on a chair, slumped sitting on a chair, and sitting on the floor. Three load modes (flexion, lateral bending, and axial rotation) were applied to the FEM, simulating movements of the lumbar spine. Results showed no significant difference in pressure distribution on the annulus fiber and nucleus pulposus, representing intradiscal pressure, as well as on the cortical bone during movements between standing and erect sitting postures. However, both slumped sitting on a chair and sitting on the floor postures significantly increased pressure on the nucleus pulposus, annulus fibrosus, and cortical bone in all three movements when compared to standing or erect sitting on a chair. Notably, sitting on the floor resulted in even higher pressure on the nucleus pulposus and annulus fibers compared to slumped sitting on a chair. The decreased lumbar lordosis while sitting on the floor led to the highest increase in pressure on the annulus fiber and nucleus pulposus in the lumbar spine. In conclusion, maintaining an erect sitting position with increased lumbar lordosis during seated activities can effectively reduce intradiscal pressure and cortical bone stress associated with degenerative disc diseases and spinal deformities.