Differential effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on gene expression of collagen-modifying enzymes in human adipose tissue-derived mesenchymal stem cells.

Adipose tissue-derived mesenchymal stem cells (AT-MSCs) in combination with bone morphogenetic protein-2 (BMP-2) or transforming growth factor-beta1 (TGF-beta1) are under evaluation for bone tissue engineering. Posttranslational modification of type I collagen is essential for functional bone tissue with adequate physical and mechanical properties. We investigated whether BMP-2 (10-100 ng/mL) and/or TGF-beta1 (1-10 ng/mL) affect gene expression of alpha2(I) procollagen and collagen-modifying enzymes, that is, lysyl oxidase and lysyl hydroxylases 1, 2, and 3 (encoded by PLOD1, 2, and 3), by human AT-MSCs.

Effect of long-term preservation on the mechanical properties of cortical bone in goats.

Background And Purpose: Bones used in mechanical studies are frequently harvested from human cadavers that have been embalmed in a buffered formaldehyde solution. It has been reported that formaldehyde fixation or freezing hardly affects the mechanical properties of bone after a storage period of several weeks. However, human cadaver bones are usually stored for longer periods of time before use.

PLDLA mesh and 60/40 biphasic calcium phosphate in iliac crest regeneration in the goat.

Although morbidity of the iliac crest after grafting has been reported to occur frequently, it is the most widely used donor site. A proper regeneration of the defect could decrease morbidity. The purpose of this study was to evaluate the efficacy of two types of reconstruction of standardized critical size defects of the iliac crest after 3, 6, and 12 months.

Molecular changes in the degenerated goat intervertebral disc.

Study Design: Caprine lumbar intervertebral discs (IVD) were collected from previous studies and categorized as normal, mildly, or severely degenerated. The biochemical composition and the RNA profiles present in both the nucleus pulposus (NP) and the anulus fibrosus (AF) were analyzed.

Objective: To determine the molecular changes occurring in a disc degeneration model, evaluating the mechanism through which the degeneration develops in this model.

Adjacent segment degeneration: observations in a goat spinal fusion study.

Study Design: The adjacent discs of 13 goats, originally used in a lumbar spinal fusion model study, were analyzed for symptoms of intervertebral disc degeneration by means of magnetic resonance imaging (MRI), macroscopy, and histology. These goats were followed for 6 months and the results were compared with 6 control goats.

Objective: To evaluate the development of adjacent segment disc degeneration in vivo in a goat lumbar spinal fusion model.

Reproducible long-term disc degeneration in a large animal model.

Study Design: Twelve goats were chemically degenerated and the development of the degenerative signs was followed for 26 weeks to evaluate the progression of the induced degeneration. The results were also compared with a previous study to determine the reproducibility.

Objectives: The purpose of this study was determine whether this Chondroitinase ABC (CABC) induced goat model is reproducible and to study the development of the degeneration in time up to 26 weeks.

The clinical significance of lumbosacral transitional anomalies.

Lumbosacral transitional vertebrae (LSTV) are common congenital anomalies of the human spine. In LSTV, either the fifth lumbar vertebra may show assimilation to the sacrum (sacralisation), or the first sacral vertebra may show transition to a lumbar configuration (lumbarisation). Although the condition has an incidence of over 12% in the general population, knowledge about the exact clinical implications is still lacking.

Intravenous administration of the conditionally replicative adenovirus Ad5-Delta24RGD induces regression of osteosarcoma lung metastases.

Metastatic osteosarcoma (OS) has a very poor prognosis. New treatments are therefore wanted. The conditionally replicative adenovirus Ad5-Delta24RGD has shown promising anti-tumor effects on local cancers, including OS.

Time-dependent mechanical strength of 70/30 Poly(L, DL-lactide): shedding light on the premature failure of degradable spinal cages.

Study Design: In vitro studies on the mechanical strength of 70/30 poly(l,dl-lactic acid) (70/30 PLDLLA) cages.

Objective: To evaluate the effect of loading rate, humidity, temperature, and continuous static loading on the strength of 70/30 PLDLLA, to elucidate the mechanism of premature failure of degradable spinal cages observed in earlier studies.

Summary Of Background Data: Degradable 70/30 PLDLLA cages have been designed to withstand mechanical loads in a goat lumbar spine for at least 6 months.

Long term follow-up of a patient with disseminated spinal hydatidosis.

A rare case of a 27-year-old male patient with disseminated sacral hydatidosis is presented. Because the diagnosis was missed initially, the patient underwent only partial resection of the tumour to obtain tissue for histology. The resection was followed by deep wound infection, and re-exploration had to be performed, thereby resecting the remaining cyst tissue and the S1-S3 vertebral bodies.

The correlation between clinical, nuclear and histologic findings in a patient with Von Recklinghausen's disease.

Background: Malignant peripheral nerve sheath tumours (MPNST) are known to develop in patients with Neurofibromatosis type I (NF1) resulting in a decreased overall survival. The association between NF1 and the development of such MPNST has been investigated in detail. The biological behaviour however of multiple disseminated neurofibromas in patients with NF1 and the risk factors for malignant transformation remain unknown.

In vivo release of the antimicrobial peptide hLF1-11 from calcium phosphate cement.

We studied the release of human lactoferrin 1-11 (hLF1-11), a potent antimicrobial peptide, in an animal model. Calcium phosphate cement with 50 mg/g hLF1-11 was injected into the femoral canal of 12 rabbits. One, 3, and 7 days later, four animals were terminated, and the femora excised.

Multidisciplinary outpatient care program for patients with chronic low back pain: design of a randomized controlled trial and cost-effectiveness study [ISRCTN28478651].

Background: Chronic low back pain (LBP) is a major public and occupational health problem, which is associated with very high costs. Although medical costs for chronic LBP are high, most costs are related to productivity losses due to sick leave. In general, the prognosis for return to work (RTW) is good but a minority of patients will be absent long-term from work.

Experimental intervertebral disc degeneration induced by chondroitinase ABC in the goat.

Study Design: In 2 studies, the injection of chondroitinase ABC into intervertebral discs of mature goats was evaluated as an experimental disc degeneration model. The first study analyzed the development of degeneration in time; the second study determined the optimal enzyme concentration.

Objectives: To develop reproducible, slowly progressive disc degeneration in a large animal model.

Stem cells from adipose tissue allow challenging new concepts for regenerative medicine.

The perspective of an innovative new concept integrating tissue-engineering techniques with an established surgical technique is described. The focus is primarily on a one-step surgical procedure using adipose tissue-derived mesenchymal stem cells, a calcium phosphate scaffold as a carrier, and a bioresorbable polymer cage to facilitate spinal interbody fusion. We address the harvesting and processing of clinically relevant quantities of adipose tissue-derived mesenchymal stem cells, triggering of these stem cells toward lineage-specific differentiation, seeding of the triggered stem cells on a bioresorbable scaffold, and implantation of the resulting tissue-engineered construct.

Enhanced tumor cell kill by combined treatment with a small-molecule antagonist of mouse double minute 2 and adenoviruses encoding p53.

Strategies to treat cancer by restoring p53 tumor suppressor functions are being actively investigated. These approaches range from expressing an exogenous p53 gene in p53 mutant cancers to antagonizing a p53 inhibitor in p53 wild-type (WT) cancer cells. In addition, exogenous p53 is used to strengthen the anticancer efficacy of oncolytic adenoviruses.

Sterilization and strength of 70/30 polylactide cages: e-beam versus ethylene oxide.

Study Design: In vitro and in vivo studies on the degradation of 70/30 poly(L,DL-lactide) (PLDLLA) cages.

Objective: To evaluate the effect of e-beam and ethylene oxide sterilization on degradation and strength.

Summary Of Background Data: e-beam-sterilized PLDLLA cages were shown to maintain mechanical strength for at least 6 months during degradation studies in vitro.

Internal thoracic vessels used as pedicle graft for anastomosis with vascularized bone graft to reconstruct C7-T3 spinal defects: a new technique.

Study Design: A report of 4 cases of primary bone tumors (3 cases) or infection (1 case) at the cervicothoracic junction treated with resection-reconstruction.

Objectives: To document a new technique using the internal thoracic vessels as recipient vessels for reconstruction of the cervicothoracic spine with free vascularized fibula grafts.

Summary Of Background Data: The cervicothoracic junction is a difficult region in reconstructive spinal surgery.

A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor.

Virotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR).

Spinal tuberculosis in a 14-year-old immigrant in the Netherlands.

We present a case of Pott's disease, where the patient presented with neurological impairment due to vertebral granulomatous necrosis, needing immediate decompression and later stabilizing and reconstructive orthopaedic surgery, in order to create awareness for TB in general, especially this forgotten form of spinal tuberculosis.

Lumbar body fusion with a bioresorbable cage in a goat model is delayed by the use of a carboxymethylcellulose-stabilized collagenous rhOP-1 device.

The purpose of this study was to evaluate the efficacy of recombinant human osteogenic protein-1 (rhOP-1) with a carboxymethylcellulose-stabilized collagenous carrier as a bone graft substitute for instrumented lumbar spinal fusion in an established goat model. Twenty goats received a resorbable poly-L-lactic acid (PLLA) interbody cage packed with either rhOP-1 and its carrier or autologous bone graft. The carrier material was bovine collagen type-1 stabilized with carboxymethylcellulose.

Interobserver reliability of the Mallet score.

The interobserver reliability of the Mallet score for active shoulder function was assessed by three experienced observers in a group of 30 children with an obstetric brachial plexus lesion (mean age 7.1 years, range 4.5-10 years).

Does bioresorbable cage material influence segment stability in spinal interbody fusion?

To reduce long term complications associated with nonresorbable interbody fusion cages, bioresorbable cages are being developed. We investigated the influence of bioresorbable cage material on segment stability, intervertebral disc height and fusion in vivo using radiostereometric analysis comparing 70/30 poly(L-lactide-co-D,L-lactide) (PLDLLA) cages with titanium cages. Twenty-eight goats were randomized to receive PLDLLA (n = 21) or a titanium control (n = 7) cage at L3-L4.

Primary spinal segment stability with a stand-alone cage: in vitro evaluation of a successful goat model.

Background: Interbody cages have been developed to restore disk height and to increase stability of the spinal segment, and thereby enhance fusion. However, they often prove inadequate as a stand-alone device. It is unknown how much primary stability is required to facilitate fusion.

Polyamines modulate nitric oxide production and COX-2 gene expression in response to mechanical loading in human adipose tissue-derived mesenchymal stem cells.

For bone tissue engineering, it is important that mesenchymal stem cells (MSCs) display a bone cell-like response to mechanical loading. We have shown earlier that this response includes increased nitric oxide (NO) production and cyclooxygenase-2 (COX-2) gene expression, both of which are intimately involved in mechanical adaptation of bone. COX-2 gene expression is likely regulated by polyamines, which are organic cations implicated in cell proliferation and differentiation.