Excessive reactive oxygen species (ROS) generation in degenerative intervertebral disc (IVD) indicates the contribution of oxidative stress to IVD degeneration (IDD), giving a novel insight into the pathogenesis of IDD. ROS are crucial intermediators in the signaling network of disc cells. They regulate the matrix metabolism, proinflammatory phenotype, apoptosis, autophagy, and senescence of disc cells. Oxidative stress not only reinforces matrix degradation and inflammation, but also promotes the decrease in the number of viable and functional cells in the microenvironment of IVDs. Moreover, ROS modify matrix proteins in IVDs to cause oxidative damage of disc extracellular matrix, impairing the mechanical function of IVDs. Consequently, the progression of IDD is accelerated. Therefore, a therapeutic strategy targeting oxidative stress would provide a novel perspective for IDD treatment. Various antioxidants have been proposed as effective drugs for IDD treatment. Antioxidant supplementation suppresses ROS production in disc cells to promote the matrix synthesis of disc cells and to prevent disc cells from death and senescence in vitro. However, there is not enough in vivo evidence to support the efficiency of antioxidant supplementation to retard the process of IDD. Further investigations based on in vivo and clinical studies will be required to develop effective antioxidative therapies for IDD.

Minimally invasive lumbar fusion techniques have only recently been developed. The goals of these procedures are to reduce approach-related soft tissue injury, postoperative pain and disability while allowing the surgery to be conducted in an effective manner. There have been no prospective clinical reports published on the comparison of one-level transforaminal lumbar interbody fusion in low-grade spondylolisthesis performed with an independent blade retractor system or a traditional open approach. A prospective clinical study of 85 consecutive cases of degenerative and isthmic lower grade spondylolisthesis treated by minimally invasive transforaminal lumbar interbody fusion (MiTLIF) or open transforaminal lumbar interbody fusion (OTLIF) was done. A total of 85 patients suffering from degenerative spondylolisthesis (n = 46) and isthmic spondylolisthesis (n = 39) underwent one-level MiTLIF (n = 42) and OTLIF (n = 43) by two experienced surgeons at one hospital, from June 2006 to March 2008 (minimum 13-month follow-up). The following data were compared between the two groups: the clinical and radiographic results, operative time, blood loss, transfusion needs, X-ray exposure time, postoperative back pain, length of hospital stay, and complications. Clinical outcome was assessed using the visual analog scale (VAS) and the Oswestry disability index. The operative time, clinical and radiographic results were basically identical in both groups. Comparing with the OTLIF group, the MiT-LIF group had significantly lesser blood loss, lesser need for transfusion, lesser postoperative back pain, and shorter length of hospital stay. The radiation time was significantly longer in MiTLIF group. One case of nonunion was observed from each group. Minimally invasive TLIF has similar surgical efficacy with the traditional open TLIF in treating one-level lower grade degenerative or isthmic spondylolisthesis. The minimally invasive technique offers several potential advantages including smaller incisions, less tissue trauma and quicker recovery. However, this technique needs longer X-ray exposure time.

The accumulation of senescent disc cells in degenerative intervertebral disc (IVD) suggests the detrimental roles of cell senescence in the pathogenesis of intervertebral disc degeneration (IDD). Disc cell senescence decreased the number of functional cells in IVD. Moreover, the senescent disc cells were supposed to accelerate the process of IDD via their aberrant paracrine effects by which senescent cells cause the senescence of neighboring cells and enhance the matrix catabolism and inflammation in IVD. Thus, anti-senescence has been proposed as a novel therapeutic target for IDD. However, the development of anti-senescence therapy is based on our understanding of the molecular mechanism of disc cell senescence. In this review, we focused on the molecular mechanism of disc cell senescence, including the causes and various molecular pathways. We found that, during the process of IDD, age-related damages together with degenerative external stimuli activated both p53-p21-Rb and p16-Rb pathways to induce disc cell senescence. Meanwhile, disc cell senescence was regulated by multiple signaling pathways, suggesting the complex regulating network of disc cell senescence. To understand the mechanism of disc cell senescence better contributes to developing the anti-senescence-based therapies for IDD.

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Mesenchymal stem cells (MSCs) have been reported to hold promise to accelerate the wound-healing process in diabetic foot ulcer (DFU) due to the multilineage differentiation potential. Hence, this study intended to explore the wound healing role of MSC-derived exosomes containing long noncoding RNA (lncRNA) H19 in DFU. lncRNA H19 was predicated to bind to microRNA-152-3p (miR-152-3p), which targeted phosphatase and tensin homolog (PTEN) deleted on chromosome ten. Fibroblasts in DFU samples exhibited highly expressed miR-152-3p and poorly expressed lncRNA H19 and PTEN, along with an activated phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt1) signaling pathway. The fibroblasts were cocultured with lncRNA H19-transfected MSCs and MSC-derived exosomes to assess the effect of the lncRNA H19/miR-152-3p/PTEN axis on the biological activities and inflammation in fibroblasts. Mouse models of DFU were developed by streptozotocin, which was injected with MSC-derived exosomes overexpressing lncRNA H19. lncRNA H19 in MSCs was transferred through exosomes to fibroblasts, the mechanism of which improved wound healing in DFU, corresponded to promoted fibroblast proliferation and migration, as well as suppressed apoptosis and inflammation. Wound healing in mice with DFU was facilitated following the injection of MSC-derived exosomes overexpressing lncRNA H19. Taken together, MSC-derived exosomal lncRNA H19 prevented the apoptosis and inflammation of fibroblasts by impairing miR-152-3p-mediated PTEN inhibition, leading to the stimulated wound-healing process in DFU.

Mesenchymal stem cells (MSCs) derived from adult tissues are an important candidate for cell-based therapies and regenerative medicine due to their multipotential differentiation capability. MSCs have been identified in many adult tissues but have not reported in the human intervertebral disc cartilage endplate (CEP). The initial purpose of this study was to determine whether MSCs exist in the degenerated human CEP. Next, the morphology, proliferation capacity, cell cycle, cell surface epitope profile and differentiation capacity of these CEP-derived stem cells (CESCs) were compared with bone-marrow MSCs (BM-MSCs). Lastly, whether CESCs are a suitable candidate for BM-MSCs was evaluated. Isolated cells from degenerated human CEP were seeded in an agarose suspension culture system to screen the proliferative cell clusters. Cell clusters were chosen and expanded in vitro and were compared with BM-MSCs derived from the same patient. The morphology, proliferation rate, cell cycle, immunophenotype and stem cell gene expression of the CESCs were similar to BM-MSCs. In addition, the CESCs could be induced into osteoblasts, adipocytes, chondrocytes, and are superior to BM-MSCs in terms of osteogenesis and chondrogenesis. This study is first to demonstrate the presence of stem cells in the human degenerated CEP. These results may improve our understanding of intervertebral disc (IVD) pathophysiology and the degeneration process, and could provide cell candidates for cell-based regenerative medicine and tissue engineering.

Object The main objective of this study was to analyze the epidemiological data obtained from patients with traumatic spinal fracture at 2 university-affiliated hospitals in Chongqing, China. Methods The authors retrospectively reviewed the hospital records of all patients who suffered traumatic spinal fracture and were treated at Xinqiao Hospital and Southwest Hospital (both affiliated with The Third Military Medical University) between January 2001 and December 2010. The demographic characteristics, injury characteristics, and clinical outcomes of patients over this 10-year period were compared. Results A total of 3142 patients (mean age 45.7 years, range 1–92 years) with traumatic spinal fractures were identified; 65.5% of the patients were male. The peak frequency of these injuries occurred in the 31- to 40-year-old age group. Accidental falls and traffic accidents were the most common causes of spinal fractures (58.9% and 20.9%, respectively). Traffic accidents tended to occur in younger patients, whereas accidental falls tended to occur in older patients. The most common area of fracture was the thoracolumbar spine (54.9%). Cervical spinal fractures were significantly more common in patients injured in traffic accidents, while lumbar spinal fractures were more common in accidental fall patients. Using the American Spinal Injury Association (ASIA) classification, 479 (15.3%) patients were classified as having ASIA A injuries; 913 (29.1%), ASIA B, ASIA C, or ASIA D; and 1750 (55.7%), ASIA E. ASIA A injuries were more common in patients who suffered thoracic spinal fractures (15.09%) than in those with fractures in other areas of the spine. A total of 954 (30.4%) patients had associated nonspinal injuries. Of these patients, 389 (40.78%) suffered a thoracic injury, and 191 (20.02%) sustained a head and neck injury. The length of hospitalization differed significantly between the accidental falls from high heights and falls from low heights, as did the mean cost of hospitalization (p < 0.05), but no significant difference was found between accidental falls from high heights and traffic accidents (p > 0.05). The length of hospitalization differed significantly among the 3 groups according to the ASIA classification, as did the mean cost of hospitalization (p < 0.05). Of patients with incomplete lesions, 39.3% improved 1 or more grades in ASIA classification during hospitalization. Conclusions Accidental falls emerged as the leading cause of traumatic spinal fracture in this study, and the numbers of fall-induced and sports-related injuries increased steadily with age. These results indicate that there should be increased concern for the consequences of fall- and sports-related injuries among the elderly.

BackgroundThe stem cell-based therapies for intervertebral disc degeneration have been widely studied. However, the mechanisms of mesenchymal stem cells interacting with intervertebral disc cells, such as nucleus pulposus cells (NPCs), remain unknown. Exosomes as a vital paracrine mechanism in cell–cell communication have been highly focused on. The purpose of this study was to detect the role of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) and NPCs in their interaction with corresponding cells.MethodsThe exosomes secreted by BM-MSCs and NPCs were purified by differential centrifugation and identified by transmission electron microscope and immunoblot analysis of exosomal marker proteins. Fluorescence confocal microscopy was used to examine the uptake of exosomes by recipient cells. The effects of NPC exosomes on the migration and differentiation of BM-MSCs were determined by transwell migration assays and quantitative RT-PCR analysis of NPC phenotypic genes. Western blot analysis was performed to examine proteins such as aggrecan, sox-9, collagen II and hif-1α in the induced BM-MSCs. Proliferation and the gene expression profile of NPCs induced by BM-MSC exosomes were measured by Cell Counting Kit-8 and qRT-PCR analysis, respectively.ResultsBoth the NPCs and BM-MSCs secreted exosomes, and these exosomes underwent uptake by the corresponding cells. NPC-derived exosomes promoted BM-MSC migration and induced BM-MSC differentiation to a nucleus pulposus-like phenotype. BM-MSC-derived exosomes promoted NPC proliferation and healthier extracellular matrix production in the degenerate NPCs.ConclusionOur study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs. Given a variety of functions and multiple advantages, exosomes alone or loaded with specific genes and drugs would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.