The functions of mesenchymal stem cells (MSCs) appear to decline with age due to cellular senescence, which could reduce the efficacy of MSCs-based therapies. Recently, MSCs have been identified in the nucleus pulposus, which offers great potential for intervertebral disc (IVD) repair. However, this potential might be affected by the senescence of nucleus pulposus MSCs (NPMSCs), but whether or not this exists remains unknown. The aim of this study was to investigate the age-related changes in NPMSCs. NPMSCs isolated from young (3-month-old) and old (14-month-old) Sprague-Dawley rats were cultured in vitro. Differences in morphology, proliferation, colony formation, multilineage differentiation, cell cycle, and expression ofβ-galactosidase (SA-β-gal) and senescent markers (p53, p21, and p16) were compared between groups. Both young and old NPMSCs fulfilled the criteria for definition as MSCs. Moreover, young NPMSCs presented better proliferation, colony-forming, and multilineage differentiation capacities than old NPMSCs. Old NPMSCs displayed senescent features, including significantly increased G0/G1 phase arrest, increased SA-β-gal expression, decreased S phase entry, and significant p53-p21-pRB pathway activation. Therefore, this is the first study demonstrating that senescent NPMSCs accumulate in IVD with age. The efficacy of NPMSCs is compromised by donor age, which should be taken into consideration prior to clinical application.
To carry out a systematic review on the basis of overlapping meta-analyses that compare unilateral with bilateral pedicle screw fixation (PSF) in lumbar fusion to identify which study represents the current best evidence, and to provide recommendations of treatment on this topic. A comprehensive literature search in PubMed, Embase, and the Cochrane Library databases was conducted to identify meta-analyses that compare unilateral with bilateral PSF in lumbar fusion. Only meta-analyses exclusively covering randomized controlled trials were included. Study quality was evaluated using the Oxford Levels of Evidence and Assessment of Multiple Systematic Reviews (AMSTAR) instrument. Then, the Jadad decision algorithm was applied to select the highest-quality study to represent the current best evidence. A total of 9 studies with Level II of evidence fulfilled the eligibility criteria and were included. The scores of AMSTAR criteria for them varied from 5 to 9 (mean 7.78). The current best evidence detected no significant differences between unilateral and bilateral PSF for short-segment lumbar fusion in the functional scores, length of hospital stay, fusion rate, and complication rate. However, unilateral PSF involved a remarkable decrease in operative time and blood loss but increase of cage migration when compared with bilateral PSF. According to this systematic review, unilateral PSF is an effective method of fixation for short-segment lumbar fusion, has the advantages of reduced operative time and blood loss over bilateral PSF, but increases the risk of cage migration.
Nucleus pulposus cells (NPCs) play a vital role in maintaining the homeostasis of the intervertebral disc (IVD). Previous studies have discovered that NPCs exhibited malfunction due to cellular senescence during disc aging and degeneration; this might be one of the key factors of IVD degeneration. Thus, we conducted this study in order to investigate the altered biofunction and the underlying genes and pathways of senescent NPCs. We isolated and identified NPCs from the tail discs of young (2 months) and old (24 months) SD rats and confirmed the senescent phenotype through SA-β-gal staining. CCK-8 assay, transwell assay, and cell scratch assay were adopted to detect the proliferous and migratory ability of two groups. Then, a rat Gene Chip Clariom™ S array was used to detect differentially expressed genes (DEGs). After rigorous bioinformatics analysis of the raw data, totally, 1038 differentially expressed genes with a were identified out of 23189 probes. Among them, 617 were upregulated and 421 were downregulated. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted and revealed numerous number of enriched GO terms and signaling pathways associated with senescence of NPCs. A protein-protein interaction (PPI) network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and Cytoscape software. Module analysis was conducted for the PPI network using the MCODE plugin in Cytoscape. Hub genes were identified by the CytoHubba plugin in Cytoscape. Derived 5 hub genes and most significantly up- or downregulated genes were further verified by real-time PCR. The present study investigated underlying mechanisms in the senescence of NPCs on a genome-wide scale. The illumination of molecular mechanisms of NPCs senescence may assist the development of novel biological methods to treat degenerative disc diseases.
Background. In this study, it was aimed to investigate the clinical rehabilitation effect of lower-limb training on the patients that undergo oblique lumbar interbody fusion (OLIF) procedures. Methods. The eligible participants undergoing OLIF procedures between 01/2017 and 07/2019 were identified. All the patients underwent one-segment fusion operation (L3-4 or L4-5). Based on whether the participants received postoperative rehabilitation training, they were divided into two groups: intervention group and control group. Postoperatively, the participants in the intervention group were trained with lower-extremity rehabilitation exercise and maintained for three months. All participants got reexamined at the first postoperative week, the second postoperative week, the first postoperative month, and the third postoperative month (last follow-up). Comparisons were made in terms of the lower-extremity muscle force, visual analogue scale (VAS) score, lumbar JOA score, Oswestry disability index (ODI), the incidence of deep venous thrombosis (DVT), and patient satisfaction. Results. Seventy-seven participants in the intervention group (32 males and 45 females) and 82 in the control group (39 males and 43 females) were incorporated in this study. The median age of the participants was 57 years (39∼73) in the intervention group and 54 years (35∼71) in the control group. No statistical significance between the two groups was found (). ODI score was less in the intervention group as compared to the control group in the first week after surgery (). VAS and JOA scores were better in the intervention group in the first two weeks after surgery (). DVT incidence in the intervention group was lower than the control group at final follow-up (). Both group participants have achieved good grading in muscle force rehabilitation but no significant differences between the two groups. Additionally, satisfaction was higher in the intervention group than the control group. Conclusions. In summary, postoperative lower-extremity rehabilitation exercise can effectively accelerate patients’ health recovery from the OLIF surgery and increase their satisfaction.
Objectives. To evaluate the effects of the limiting dilution method and plating density in rat nucleus pulposus mesenchymal stem/progenitor cells (NPMSCs). Materials and Methods. Nucleus pulposus tissues were isolated from 12-week-old male Sprague-Dawley rats and NPMSCs were isolated using limiting dilution method. Cells were then classified into 3 groups according to plating density. Cell morphologies were observed, and colony-forming units, migration abilities, proliferative capacities, cell cycle percentages, multilineage differentiation capacities, stem cell biomarker expression levels, and immunophenotyping were also examined in each group. Results. Low density group (LD) had higher morphological homogeneity, stronger colony-forming ability, higher cell proliferation capacity, and enhanced cell migration ability relative to the other two groups (). Moreover, LD had more cells entering S phase, with fewer cells arrested in G0/G1 phase (). While all three density groups showed a multilineage differentiation potential, LD showed a higher degree of observed and semiquantified lineage specific staining (). Furthermore, LD displayed higher expression levels of stem cell biomarkers (Nanog, Oct4, and Sox2) and showed higher percentages of CD29+, CD44+, and CD90+ cells () following flow cytometry analysis. Conclusions. Limiting dilution method is suggested when isolating NPMSCs as a means of improving cell activity and plasticity.