Fei Dai

Surgical strategy and management outcomes for adjacent multisegmental spinal tuberculosis: a retrospective study of forty-eight patients.

Study Design. Retrospective study. Objective. To evaluate the clinical outcomes of 4 different procedures for the treatment of adjacent multisegmental spinal tuberculosis (AMSST) and to investigate the selection strategy of the optimal procedure with respect to focal characteristics. Summary of Background Data. Because of the lack of support of the anterior columns of multiple segments, AMSST is thought to confer high risks for the development of kyphosis and paraplegia. However, there are few reports regarding the clinical outcomes of the surgical treatment for AMSST have been investigated. Methods. From August 1999 to June 2010, 48 patients with AMSST were enrolled in this study. Seven patients (A group) underwent a single-stage anterior operation. Eighteen patients (AP group) underwent a single-stage posterior and anterior combined operation. Eighteen patients (P group) underwent a single-stage posterior operation. Five patients (DP group) underwent computed tomography-guided drainage and local chemotherapy combined with a 2-stage posterior operation. The patients were followed up clinically and radiologically for an average of 29.6 months. Results. The cohort consisted of 29 males and 19 females, aged 4 to 54 years. The patients exhibited significant improvements in deformity and neurological deficits. Graft union was achieved in all patients 5 to 12 months postoperatively. Surgery-related complications were noted in 1 and 2 patients in the AP and P groups, respectively. Postoperative recurrence occurred in 1 and 2 patients in the AP and P groups, respectively. All 48 patients had been cured at the final follow-up. Conclusion. This study demonstrated that the 4 procedures can safely and effectively achieve nerve decompression, graft fusion, and kyphosis correction. Individualized procedures should be chosen according to the patients general condition, focal characteristic, type of complication, and surgeons experience. Level of Evidence: 3

Surgical treatment of the osteoporotic spine with bone cement-injectable cannulated pedicle screw fixation: technical description and preliminary application in 43 patients.

OBJECTIVES: To describe a new approach for the application of polymethylmethacrylate augmentation of bone cement-injectable cannulated pedicle screws. METHODS: Between June 2010 and February 2013, 43 patients with degenerative spinal disease and osteoporosis (T-score <-2.5) underwent lumbar fusion using cement-injectable cannulated pedicle screws. Clinical outcomes were evaluated using a Visual Analog Scale and the Oswestry Disability Index. Patients were given radiographic follow-up examinations after 3, 6, and 12 months and once per year thereafter. RESULTS: All patients were followed for a mean of 15.7±5.6 months (range, 6 to 35 months). The Visual Analog Scale and Oswestry Disability Index scores showed a significant reduction in back pain (p = 0.018) and an improvement in lower extremity function (p = 0.025) in patients who underwent lumbar fusion using the novel screw. Intraoperative cement leakage occurred in four patients, but no neurological complications were observed. Radiological observation indicated no loosening or pulling out of the novel screw, and bone fusion was excellent. CONCLUSIONS: The described polymethylmethacrylate augmentation technique using bone cement-injectable cannulated pedicle screws can reduce pain and improve spinal dysfunction in osteoporotic patients undergoing osteoporotic spine surgery.

Periostin Upregulates Wnt/β-Catenin Signaling to Promote the Osteogenesis of CTLA4- Modified Human Bone Marrow-Mesenchymal Stem Cells

The enhanced osteogenesis of mesenchymal stem cells (MSCs) modified by expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) has been shown in previous studies, but the mechanism remains unknown. Here we found that the bone repair effect of CTLA4-modified MSCs in demineralized bone matrix (DBM) in a rabbit radius defect model was significantly better than that observed for unmodified MSCs in DBM or DBM alone, and the periostin (POSTN) expression in CTLA4-modified MSCs was significantly higher than that in unmodified MSCs both in vivo and in vitro. In addition, we also found that treatment of CTLA4-modified MSCs with soluble POSTN could inhibit the glycogen synthase kinase-3β activity and increase β-catenin expression through up-regulation of lipoprotein-related protein-6 phosphorylation to promote osteogenic differentiation, but blocking of integrin αvβ3, a receptor of POSTN, could suppress these effects. Our data demonstrated that POSTN expressed in response to CTLA4 can promote the osteogenesis of xenotransplanted MSCs through interaction with Wnt/β-catenin pathway.

Repeated microendoscopic discectomy for recurrent lumbar disk herniation

OBJECTIVES: To explore the microendoscopic discectomy technique and inclusion criteria for the treatment of recurrent lumbar disc herniation and to supply feasible criteria and technical notes to avoid complications and to increase the therapeutic effect. METHODS: A consecutive series of 25 patients who underwent posterior microendoscopic discectomy for recurrent lumbar disc herniation were included. The inclusion criteria were as follows: no severe pain in the lumbar region, no lumbar instability observed by flexion-extension radiography and no intervertebral discitis or endplate damage observed by magnetic resonance imaging. All patients were diagnosed by clinical manifestations and imaging examinations. RESULTS: Follow-up visits were carried out in all cases. Complications, such as nerve injuries, were not observed. The follow-up outcomes were graded using the MacNab criteria. A grade of excellent was given to 12 patients, good to 12 patients and fair to 1 patient. A grade of excellent or good occurred in 96% of cases. One patient relapsed 3 months after surgery and then underwent lumbar interbody fusion and inner fixation. The numerical rating scale of preoperative leg pain was 7.4± 1.5, whereas it decreased to 2.1±0.8 at 7 days after surgery. The preoperative Oswestry disability index of lumbar function was 57.5±10.0, whereas it was 26.0±8.5 at 7 days after surgery. CONCLUSION: In these cases, microendoscopic discectomy was able to achieve satisfactory clinical results. Furthermore, it has advantages over other methods because of its smaller incision, reduced bleeding and more efficient recovery.

Genome-wide association study for osteoarthritis

Robert Kirsner and colleagues (Sept 15, p 977) describe a spray formulation of allogeneic neonatal keratinocytes and fi broblasts for the treatment of chronic venous leg ulcers. Such therapies are novel and of major interest. However, although this technique certainly has potential, we have some concerns about the interpretation of the results of Kirsner and colleagues’ study. First, it is not clear whether Kirsner and co-workers tested the viability of the fibroblasts and keratinocytes. Viable cells are crucial in the treatment of ulcers. Second, why are there no representative fi gures to show that wound healing was greater with 0·5×106 cells/mL every 14 days than with vehicle alone? Third, the follow-up (12 weeks) was too short to show the eff ect of spray-applied cell therapy with human allogeneic fi broblasts and keratinocytes on longterm outcomes. Were there any such follow-up fi ndings with regard to this technology? Finally, this spray-applied cell therapy contains compound solutions, including cells and matrix. It would be interesting to know which part is responsible for the clinical eff ects, and whether the mechanisms of action are direct (diff erentiation into myofi broblast or vascular endothelial cells), indirect (cell–cell contact or paracrine eff ects), or both.

hTERT- and hCTLA4Ig-expressing human bone marrow-derived mesenchymal stem cells: in vitro and in vivo characterization and osteogenic differentiation.

Multipotent mesenchymal stem cells (MSCs) are commonly used as seed cells in studies of tissue engineering and regenerative medicine but their clinical application is limited, due to insufficient numbers of autogeneic MSCs, immune rejection of allogeneic MSCs and replicative senescence. We constructed two gene expression vectors for transfection of the human telomerase reverse transcriptase (hTERT) and cytotoxic T lymphocyte‐associated antigen 4‐Ig (CTLA4Ig) genes into human bone marrow‐derived stem cells (hBMSCs). Successful transfection of both genes generated hTERT–CTLA4Ig hBMSCs that expressed both telomerase (shown by immunohistochemistry and a TRAPeze assay) and CTLA4Ig (demonstrated by immunocytochemistry and western blotting) without apparent mutual interference. Both hTERT BMSCs (92 population doublings) and hTERT–CTLA4Ig hBMSCs (60 population doublings) had an extended lifespan compared with hBMSCs (18 population doublings). Cell cycle analysis revealed that, compared with hBMSCs, a lower proportion of hTERT hBMSCs were in G0/G1 phase but a higher proportion were in S phase; compared with hTERT hBMSCs, a higher proportion of hTERT–CTLA4Ig hBMSCs were in G0/G1 phase, while a lower proportion were in S and G2/M phases. hTERT–CTLA4Ig hBMSCs retained their capacity for osteogenic differentiation in vitro, shown by the detection of hydroxyapatite mineral deposition (labelled tetracycline fluorescence staining), calcareous nodules (alizarin red S staining), alkaline phosphatase (calcium–cobalt method) and osteocalcin (immunocytochemistry). Furthermore, subcutaneous transplantation of hTERT–CTLA4Ig hBMSCs in a rat xenotransplantation model resulted in the successful generation of bone‐like tissue, confirmed using radiography and histological assessment. We propose that allogeneic hTERT–CTLA4Ig hBMSCs may be ideal seed cells for bone tissue engineering. Copyright

Periostin: A Downstream Mediator of EphB4-Induced Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells

Erythropoietin-producing hepatocyte B4 (EphB4) has been reported to be a key molecular switch in the regulation of bone homeostasis, but the underlying mechanism remains poorly understood. In this study, we investigated the role of EphB4 in regulating the expression of periostin (POSTN) within bone marrow-derived mesenchymal stem cells (MSCs) and assessed its effect and molecular mechanism of osteogenic induction in vitro. Treatment with ephrinB2-FC significantly increased the expression of POSTN in MSCs, and the inhibition of EphB4 could abrogate this effect. In addition, osteogenic markers were upregulated especially in MSCs overexpressing EphB4. To elucidate the underlying mechanism of cross talk between EphB4 and the Wnt pathway, we detected the change in protein expression of phosphorylated-glycogen synthase kinase 3β-serine 9 (p-GSK-3β-Ser9) and β-catenin, as well as the osteogenic markers Runx2 and COL1. The results showed that GSK-3β activation and osteogenic marker expression levels were downregulated by ephrinB2-FC treatment, but these effects were inhibited by blocking integrin αvβ3 in MSCs. Our findings demonstrate that EphB4 can promote osteogenic differentiation of MSCs via upregulation of POSTN expression. It not only helps to reveal the interaction mechanism between EphB4 and Wnt pathway but also brings a better understanding of EphB4/ephrinB2 signaling in bone homeostasis.

Improved Monosegment Pedicle Instrumentation for Treatment of Thoracolumbar Incomplete Burst Fractures

Aim. Comparing the clinical results of improved monosegment pedicle instrumentation (iMSPI) and short-segment pedicle instrumentation (SSPI) retrospectively. Method. 63 patients with thoracolumbar incomplete burst fracture were managed with iMSPI or SSPI. 30 patients were managed with iMSPI and fusion. 33 patients were managed with SSPI and fusion. Operative time, blood loss, postoperative drainage, and complications were recorded. Percentage of anterior body height compression (ABHC%) and sagittal index (SI) were obtained preoperatively, one week postoperatively, and at the last followup. Results. The blood loss and postoperative drainage were significantly less in the iMSPI group than in SSPI group (P < 0.05). The follow-up duration of the two groups was not significantly different (P > 0.05). At 12 months postoperatively posterolateral fusion was obtained satisfactorily. Neither preoperative ABHC% and SI nor postoperative SI were significantly different (P > 0.05), but there was a significant difference in postoperative ABHC% (P = 0.000). The ABHC% and SI were not significantly different between the two groups at the last followup (P > 0.05). There were no fixation failures or other complications. Summary. IMSPI yielded satisfactory results similar to those of SSPI in patients with type A3.1/3.2 thoracolumbar fractures. IMSPI is recommended for minor trauma, reducing one-segment fusion, and maximization of the remaining motor function.

Biomechanical and finite element analyses of bone cement‐Injectable cannulated pedicle screw fixation in osteoporotic bone

The objectives of this study were to investigate the safety and biomechanical stability of a polymethylmethacrylate (PMMA)-augmented bone cement-injectable cannulated pedicle screw (CICPS) in cancellous bone model, and to analyze the stress distribution at the screw-cement-bone interface. The OMEGA cannulated pedicle screw (OPS) and conventional pedicle screw (CPS) were used as control groups. Safety of the CICPS was evaluated by the static bending and bending fatigue tests. Biomechanical stability was analyzed by the maximum axial pullout strength and maximum torque tests. Stress distribution at the screw-cement-bone interface was analyzed by the finite element (FE) method. The CICPS and CPS produced statistically similar values for bending stiffness, bending structural stiffness, and bending yield moment. The maximum pullout force was 53.47 ± 8.65 N in CPS group, compared to 130.82 ± 7.32 N and 175.45 ± 43.01 N in the PMMA-augmented OPS and CICPS groups, respectively (p < 0.05). The CICPS had a significantly greater torque than the OPS and CPS. The FE model did not reveal excessive stress at the screw-cement-bone interface in the CICPS group. In conclusion, PMMA-augmentation with CICPS may be a potentially useful method to increase the stability of pedicle screws in patients with osteoporosis.

CTLA4 enhances the osteogenic differentiation of allogeneic human mesenchymal stem cells in a model of immune activation

Allogeneic mesenchymal stem cells (allo-MSCs) have recently garnered increasing interest for their broad clinical therapy applications. Despite this, many studies have shown that allo-MSCs are associated with a high rate of graft rejection unless immunosuppressive therapy is administered to control allo-immune responses. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is a co-inhibitory molecule expressed on T cells that mediates the inhibition of T-cell function. Here, we investigated the osteogenic differentiation potency of allo-MSCs in an activated immune system that mimics the in vivo allo-MSC grafting microenvironment and explored the immunomodulatory role of the helper T cell receptorCTLA4 in this process. We found that MSC osteogenic differentiation was inhibited in the presence of the activated immune response and that overexpression of CTLA4 in allo-MSCs suppressed the immune response and promoted osteogenic differentiation. Our results support the application of CTLA4-overexpressing allo-MSCs in bone tissue engineering.