Bioactive suture: a novel immunotherapy for head and neck cancer.

PURPOSE: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T(H)1 immune response and to define the immune-stimulating half-life of the sutures. EXPERIMENTAL DESIGN: Bioactive sutures of interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor kappaB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132. RESULTS: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma generated a prolonged T(H)1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-kappaB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression. CONCLUSIONS: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged T(H)1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients.     

Myoblast therapy for stress urinary incontinence and bladder dysfunction

The field of tissue engineering and gene therapy has an exciting and promising future. During the past few years we have begun a comprehensive effort to investigate the use of myoblasts to improve and expand the treatment of stress urinary incontinence and bladder dysfunction. Moreover, we can expect the application of myoblast-mediated ex vivo gene transfer in the field of urology. In this paper we discuss the compositions of and methods involving the use of myogenic or muscle-derived cells for tissue engineering and cell-mediated gene therapy.     

Tissue engineering and gene therapy of the musculoskeletal system with muscle cells

AIM: Muscle-based somatic gene therapy is a novel way to alleviate a biochemical deficiency. METHOD: Muscle-derived cells are very promising in the field of gene therapy and tissue engineering. First, most muscle tissue is accessible by injection. Second, muscle tissue consists of multinucleated, postmitotic myofibers, which enable a long-term expression of the transduced gene. Third, muscle tissue can be biopsied easily. It is available in abundance and the biopsy does not compromise the health and function of the patient. Finally, muscle tissue is highly vascularized, which makes systemic delivery feasible. RESULTS: Muscle-derived cells can promote muscle healing and bone healing. Implanted cells maintain a long-term transgene expression of therapeutic proteins. Isolated, muscle-derived stem cells can differentiate in osteoblasts. CONCLUSION: Based on these characteristics, we present four possible applications: inherited muscular diseases, muscle injury, bone healing, and intraarticular disorders.     

Ex vivo gene therapy to produce bone using different cell types

Gene therapy and tissue engineering promise to revolutionize orthopaedic surgery. This study comprehensively compares five different cell types in ex vivo gene therapy to produce bone. The cell types include a bone marrow stromal cell line, primary muscle derived cells, primary bone marrow stromal cells, primary articular chondrocytes, and primary fibroblasts. After transduction by an adenovirus encoding for bone morphogenetic protein-2, all of the cell types were capable of secreting bone morphogenetic protein-2. However, the bone marrow stromal cell line and muscle derived cells showed more responsiveness to recombinant human bone morphogenetic protein-2 than did the other cell types. In vivo injection of each of the cell populations transduced to secrete bone morphogenetic protein-2 resulted in bone formation. Radiographic and histologic analyses corroborated the in vitro data regarding bone morphogenetic protein-2 secretion and cellular osteocompetence. This study showed the feasibility of using primary bone marrow stromal cells, primary muscle derived cells, primary articular chondrocytes, primary fibroblasts, and an osteogenesis imperfecta stromal cell line in ex vivo gene therapy to produce bone. The study also showed the advantages and disadvantages inherent in using each cell type.     

Insight opinion to surgically treated metastatic bone disease: Scandinavian Sarcoma Group Skeletal Metastasis Registry report of 1195 operated skeletal metastasis

The number of cancer patients living with metastatic disease is growing. The increased survival has led to an increase in the number of cancer-induced complications, such as pathologic fractures due to bone metastases. Surgery is most commonly needed for mechanical complications, such as fractures and intractable pain. We determined survival, disease free interval and complications in surgically treated bone metastasis. Data were collected from the Scandinavian Skeletal Metastasis Registry for patients with extremity skeletal metastases surgically treated at eight major Scandinavian referral centres between 1999 and 2009 covering a total of 1195 skeletal metastases in 1107 patients. Primary breast, prostate, renal, lung, and myeloma tumors make up 78% of the tumors. Number of complications is tolerable and is affected by methods of surgery as well as preoperative radiation therapy. Overall 1-year patient survival was 36%; however, mean survival was influenced by the primary tumor type and the presence of additional visceral metastases. Patients with impending fracture had more systemic complications than those with complete fracture. Although surgery is usually only a palliative treatment, patients can survive for years after surgery. We developed a simple, useful and reliable scoring system to predict survival among these patients. This scoring system gives good aid in predicting the prognosis when selecting the surgical method. While it is important to avoid unnecessary operations, operating when necessary can provide benefit.     

Temporal structure/function variation in cultured differentiated human nasal epithelium associated with acute single exposure to tobacco smoke or E-cigarette vapor

Objective: Mucociliary clearance sustains a baseline functionality and an “on demand” capability to upregulate clearance upon irritant exposure involving mucus hypersecretion and accelerated ciliary beat frequency (CBF) modulated by nitric oxide (NO). This study characterized these elements as well as cellular and exogenous NO concentrations subsequent to a single exposure to tobacco smoke (TS) or e-cigarette vapor (EV) on cultured human airway epithelium.

Materials and methods: Air–liquid interface (ALI) airway epithelial cultures per nonsmoking human subjects were subjected to single TS or EV exposures. Measures of ciliary function and secretion were performed and cellular and exogenous NO concentrations under control and experimental conditions were assessed.

Results: Both TS and EV exposures resulted similar patterns of decline in CBF within 1?min of the completion of exposure followed by a gradual return often exceeding baseline within 1?h. Post-exposure examination of exposed cultures suggested morphologic differences in secretory function relative to controls. The relative NO concentrations of TS and EV chamber air were sharply different with EV NO being only slightly elevated relative to cellular NO production.

Discussion and conclusions: Epithelial remodeling and mucociliary dysfunction have been clearly associated with TS exposure. However, information contrasting epithelial structure/function following a single acute TS or EV exposure is limited. This study demonstrates a similar pattern of epithelial response to acute TS or EV exposure. Inasmuch as NO may contribute to an inflammatory milieu and generation of toxic metabolites, it is plausible that recurrent exposures over time may be contributory to chronic pathologies.     

Communication Skills in Children with Cerebral Palsy and Autism Spectrum Disorder

While the literature focusing on communication deficits in children with cerebral palsy (CP) is extensive, few researchers have analyzed this construct in individuals with CP and a comorbid Autism Spectrum Disorder (ASD). Therefore, the purpose of the current study was to examine impairments in communication in infants and toddlers (18 to 35 months of age) who had CP and comorbid autism, CP and comorbid pervasive developmental disorder-not otherwise specified (PDD-NOS), and CP alone. A total of 42 children met inclusion criteria for this study. Those diagnosed with CP and a comorbid ASD were found to possess significantly greater communication impairments as assessed by the Baby and Infant Screen for aUtIsm Traits-Part 1 (BISCUIT-Part 1) than participants who only had a diagnosis of CP. The autism and PDD-NOS groups did not significantly differ from one another on the communication domain of this measure, however. Implications of these results are discussed.     

Factor Structure for Autism Spectrum Disorders with Toddlers Using DSM-IV and DSM-5 Criteria

With the publication of the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition, autism spectrum disorders are defined by two symptom clusters (social communication and restricted/repetitive behaviors) instead of the current three clusters. The current study examined the structure of the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT). First, an exploratory factor analysis was replicated whose results were largely comparable to the previous findings. Then, confirmatory factor analyses compared a two and three factor structure for the BISCUIT. Measures of model fit supported both the two and three factor models relatively well. When directly compared, the three factor model was found to be preferred over the two factor model. Implications are discussed.