Co-culturing nucleus pulposus mesenchymal stem cells with notochordal cell-rich nucleus pulposus explants attenuates tumor necrosis factor-α-induced senescence.

BACKGROUND: Cell therapy for the treatment of intervertebral disc degeneration (IDD) faces serious barriers since tissue-specific adult cells such as nucleus pulposus cells (NPCs) have limited proliferative ability and poor regenerative potential; in addition, it is difficult for exogenous adult stem cells to survive the harsh environment of the degenerated intervertebral disc. Endogenous repair by nucleus pulposus mesenchymal stem cells (NPMSCs) has recently shown promising regenerative potential for the treatment of IDD. Notochordal cells (NCs) and NC-conditioned medium (NCCM) have been proven to possess regenerative ability for the treatment of IDD, but this approach is limited by the isolation and passaging of NCs. Our previous study demonstrated that modified notochordal cell-rich nucleus pulposus (NC-rich NP) has potential for the repair of IDD. However, whether this can protect NPMSCs during IDD has not been evaluated. METHODS: In the current study, tumor necrosis factor (TNF)-α was used to mimic the inflammatory environment of IDD. Human NPMSCs were cocultured with NC-rich NP explants from healthy rabbit lumbar spine with or without TNF-α. Cell proliferation and senescence were analyzed to investigate the effect of NC-rich NP explants on TNF-α-treated NPMSCs. The expression of mRNA encoding proteins related to matrix macromolecules (such as aggrecan, Sox-9, collagen Iα, and collagen IIα), markers related to the nucleus pulposus cell phenotype (including CA12, FOXF1, PAX1, and HIF-1α), and senescence markers (such as p16, p21, and p53), senescence-associated proinflammatory cytokines (IL-6), and extracellular proteases (MMP-13, ADAMTS-5) was assessed. The protein expression of CA12 and collagen II was also evaluated. RESULTS: After a 7-day treatment, the NC-rich NP explant was found to enhance cell proliferation, decrease cellular senescence, promote glycosaminoglycan (GAG), collagen II, and CA12 production, upregulate the expression of extracellular matrix (ECM)-related genes (collagen I, collagen II, SOX9, and ACAN), and enhance the expression of nucleus pulposus cell (NPC) markers (HIF-1α, FOXF1, PAX1, and CA12). CONCLUSION: Modified NC-rich NP explants can attenuate TNF-α-induced degeneration and senescence of NPMSCs in vitro. Our findings provide new insights into the therapeutic potential of NC-rich NP for the treatment of IDD.

Full-Endoscopic Procedures Versus Traditional Discectomy Surgery for Discectomy: A Systematic Review and Meta-analysis of Current Global Clinical Trials.

BACKGROUND: Traditional discectomy surgery (TDS) provides good or excellent results in clinical surgical discectomy but may induce neural adhesion, spinal structural damage, instability, and other complications. The potential advantages of full-endoscopic (FE) procedures over standard TDS include less blood loss, less postoperative pain, shorter hospitalization, and an earlier return to work. However, more evidence is needed to support this new technology in clinical applications. OBJECTIVE: The aim of this systematic review and meta-analysis was to compare the safety and efficacy of FE and TDS. STUDY DESIGN: Comprehensive systematic review and meta-analysis of the literature. METHODS: Electronic databases, including PubMed, EMBASE, SinoMed, and Cochrane Library, were searched to identify clinical therapeutic trials comparing FE to TDS for discectomy. RESULTS: Six trials comprising 730 patients were included, and the overall quality of the literature was moderate, including 4 Grade I levels of evidence (4 randomized controlled trials, [RCTs]) and 2 Grade II levels (2 non-RCTs). The pooled data revealed no difference in reoperation rates between FE and TDS (P = 0.94), but the complication rate was significantly lower in the FE group (3.86%) than in the TDS group (11.4%). Perioperative parameters (operation time, blood loss, hospitalization time, and return to work days) were significantly lower in the FE group (P < 0.05 for all groups using either score). Postoperative pain and neurology score assessments were conducted at 4 different time points at 3 months, 6 months, 12 months, and 24 months. Significant differences were detected in the following: lumbar North American Spine Society (NASS) pain at 6 months (P = 0.008); cervical NASS neurology at 6 months (P = 0.03); visual analog scale (VAS) score in leg at 3 months (P < 0.001); VAS score in arm at 24 months (P = 0.002); VAS score in neck at 3 months, 6 months, and 12 months after therapy (P = 0.003, P = 0.004, P = 0.01); and VAS score in neck at 3 months and 6 months (P = 0.01, P = 0.004). Moreover, the pooled data revealed no statistically significant differences in improvements in the Oswestry disability index (ODI), instability (X-ray), and Hilibrand criteria (P > 0.05 for all groups). LIMITATIONS: Only 6 studies were included, 4 of which had the same authors. Between-study heterogeneity due to differences in socioeconomic factors, nutrition, and matching criteria is difficult to avoid. CONCLUSIONS: Based on this meta-analysis of 24 months of clinical results, we conclude that the FE procedure is as effective as TDS but has the additional benefits of lower complication rates and superior perioperative parameters. In addition, patients may experience less pain with FE techniques due to a smaller incision and less operative injury. However, large-volume, well-designed RCTs with extensive follow-up are needed to confirm and update the findings of this analysis.

Efficacy and safety of bone marrow-derived cell transplantation for spinal cord injury: a systematic review and meta-analysis of clinical trials.

PURPOSE: Bone marrow-derived cells (BMDCs) for clinical transplantation were carried out many years in treating spinal cord injury (SCI) without a clear conclusion. This study aimed to evaluate the safety and efficacy of BMDC transplantation in treatment of SCI patients. METHOD: Electronic databases, including PubMed, EMBASE, MEDLINE, and the Cochrane library, were searched to identify clinical therapeutic trials studying the application of BMDC transplantation in SCI. RESULTS: Overall the quality of the 24 studies was low, including one Grade I level of evidence, six Grade II levels, three Grade III levels, and 14 Grade IV levels. With a maximum of six-yr follow-up, the procedure-related complications were minor and temporary, without serious adverse events (p = 0, n = 594). AIS improvement rate was analyzed in favor of BMDCs 6.13 (95% CI, 3.0-12.51; p < 0.001). In patient with complete (AIS A) and chronic SCI, the application of cell transplantation numbers between n × (10(7) -10(8) ) seemed to be more beneficial (p < 0.05 for all groups). CONCLUSIONS: Based on short-medium terms following up, BMDC transplantation appears to be safe and valid in SCI patients, more effective in chronic and complete injury. Nonetheless, prospective, randomized trials in larger cohorts are still needed.