Welcome to Wordpublish.org Body!
The concept of tissue and cell guidance is rapidly evolving as more information regarding the effect of the microenvironment on cellular function and tissue morphogenesis become available. These disclosures have lead to a tremendous advancement in the design of a new generation of multifunctional biomaterials able to mimic the molecular regulatory characteristics and the three-dimensional architecture of the native extracellular matrix. Micro- and nano-structured scaffolds able to sequester and deliver in a highly specific manner biomolecular moieties have already been proved to be effective in bone repairing, in guiding functional angiogenesis and in controlling stem cell differentiation. Although these platforms represent a first attempt to mimic the complex temporal and spatial microenvironment presented in vivo, an increased symbiosis of material engineering, drug delivery technology and cell and molecular biology may ultimately lead to biomaterials that encode the necessary signals to guide and control developmental process in tissue- and organ-specific differentiation and morphogenesis. Abbreviation list: bFGF; basic fibroblast growth factor; BMP; bone morphogenetic protein; BSA; bovine serum albumin; CASD; computer-aided scaffold design; DS; delivery systems; ECM; extracellular matrix; EGF; epidermal growth factor; EVAc; ethylene-vinyl acetate copolymers; GF; growth factor; HBDS; heparin-based delivery systems; NT-3; neurotrophin-3; PA; peptide amphiphile; PCL; poly(-caprolactone); PDGF; platelet derived growth factor; PEG; poly(ethylene glycol); PEO; poly(ethylene oxide); PLA; poly(lactide); PLGA; poly(lactide-co-glycolide); POE; poly(ortho esters); PTH; parathyroid hormone; SFF; solid free-form fabrication; TE; tissue engineering; TGF-β1; transforming growth factor-beta1; VEGF; vascular endothelial growth factor
Marco Biondia Francesca Ungaroa Fabiana Quagliaa Paolo Antonio NettiaEmail:nettipa@unina.it
[a]Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, Italy
The extracellular microenvironment plays a significant role in controlling cellular behavior. Identification of appropriate biomaterials that support cellular attachment, proliferation and, most importantly in the case of human embryonic stem cells, lineage-specific differentiation is critical for tissue engineering and cellular therapy. In addition to growth factors and morphogenetic factors known to induce lineage commitment of stem cells, a number of scaffolding materials, including synthetic and naturally-derived biomaterials, have been utilized in tissue engineering approaches to direct differentiation. This review focuses on recent emerging findings and well-characterized differentiation models of human embryonic stem cells. Additionally, we also discuss about various strategies that have been used in stem cell expansion.
Nathaniel S. Hwanga Shyni Varghesea Jennifer ElisseeffaEmail:jhe@jhu.edu
[a]Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, USA
OBJECTIVE: To assess a technique for laparoscopic collection of serial full-thickness small intestinal biopsy specimens in horses. ANIMALS:13 healthy adult horses. PROCEDURES: In the ex vivo portion of the study, sections of duodenum and jejunum obtained from 6 horses immediately after euthanasia were divided into 3 segments. Each segment was randomly assigned to the control group, the double-layer hand-sewn closure group, or the endoscopic linear stapler (ELS) group. Bursting strength and bursting wall tension were measured and compared among groups; luminal diameter reduction at the biopsy site was compared between the biopsy groups. In the in vivo portion of the study, serial full-thickness small intestinal biopsy specimens were laparoscopically collected with an ELS from the descending duodenum and distal portion of the jejunum at monthly intervals in 7 sedated, standing horses. Biopsy specimens were evaluated for suitability for histologic examination. RESULTS: Mean bursting strength and bursting wall tension were significantly lower in the ELS group than in the hand-sewn and control groups in both the duodenal and jejunal segments. Use of the hand-sewn closure technique at the biopsy site reduced luminal diameter significantly more than use of the stapling technique. In the in vivo part of the study, all 52 biopsy specimens collected during 26 laparoscopic procedures were suitable for histologic examination and no clinically important perioperative complications developed. CONCLUSIONS AND CLINICAL RELEVANCE: Laparoscopic collection of serial full-thickness small intestinal biopsy specimens with a 45-mm ELS may be an effective and safe technique for use in healthy adult experimental horses.
Bracamonte JLBoure LPGeor RJRunciman JRNykamp SGCruz AMTeeter MGWaterfall HL
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
Tissue engineering and regenerative medicine is an exciting research area that aims at regenerative alternatives to harvested tissues for transplantation. Biomaterials play a pivotal role as scaffolds to provide three-dimensional templates and synthetic extracellular matrix environments for tissue regeneration. It is often beneficial for the scaffolds to mimic certain advantageous characteristics of the natural extracellular matrix, or developmental or wound healing programs. This article reviews current biomimetic materials approaches in tissue engineering. These include synthesis to achieve certain compositions or properties similar to those of the extracellular matrix, novel processing technologies to achieve structural features mimicking the extracellular matrix on various levels, approaches to emulate cell–extracellular matrix interactions, and biologic delivery strategies to recapitulate a signaling cascade or developmental/wound healing program. The article also provides examples of enhanced cellular/tissue functions and regenerative outcomes, demonstrating the excitement and significance of the biomimetic materials for tissue engineering and regeneration.
Peter X. MaaEmail:mapx@umich.edu
[a]Department of Biologic and Materials Sciences, The University of Michigan, Ann Arbor, MI 48109-1078, USA;[b]Department of Biomedical Engineering, The University of Michigan, Ann Arbor, MI 48109-1078, USA;[c]Macromolecular Science and Engineering Center, The University of Michigan, Ann Arbor, MI 48109-1078, USA
OBJECTIVE: To assess physiologic responses and plasma endothelin (ET)-1 concentrations associated with abrupt cessation of nitric oxide (NO) inhalation in isoflurane-anesthetized horses. ANIMALS: 6 healthy adult Standardbreds. PROCEDURES: Horses were anesthetized with isoflurane in oxygen and placed in dorsal recumbency. Nitric oxide was pulsed into the respiratory tract for 2.5 hours, and then administration was abruptly discontinued. Just prior to commencement and at cessation of NO administration, and at intervals during a 30-minute period following cessation of NO inhalation, several variables including PaO(2), mean pulmonary artery pressure, venous admixture or pulmonary shunt fraction (Qs/Qt), and plasma ET-1 concentration were recorded or calculated. RESULTS: After cessation of NO inhalation, PaO(2) decreased slowly but significantly (172.7 +/- 29.8 mm Hg to 84.6 +/- 10.9 mm Hg) and Qs/Qt increased slowly but significantly (25 +/- 2% to 40 +/- 3%) over a 30-minute period. Mean pulmonary artery pressure increased slightly (14.0 +/- 1.3 mm Hg to 16.8 +/- 1 mm Hg) over the same time period. No change in serum ET-1 concentration was detected, and other variables did not change or underwent minor changes. CONCLUSIONS AND CLINICAL RELEVANCE: The improvement in arterial oxygenation during pulsed inhalation of NO to healthy isoflurane-anesthetized horses decreased only gradually during a 30-minute period following cessation of NO inhalation, and serum ET-1 concentration was not affected. Because a rapid rebound response did not develop, inhalation of NO might be clinically useful in the treatment of hypoxemia in healthy isoflurane-anesthetized horses.
Grubb TLHogman MEdner AFrendin JHHeinonen EMalavasi LMFrostell CGRyden AAlving KNyman GC
Riverview Animal Clinic, Uniontown, WA 99179, USA.
Dendritic cells are professional antigen-presenting cells with a key role in both immunity induction and tolerance maintenance. Dendritic cells are highly specialized in antigen capture, processing and presentation, and express co-stimulation signals which activate T lymphocytes and NK cells. Dendritic cells generated in culture and loaded with an antigen efficiently induce antigen-specific immunity after injection. More recently, methods have been developed that target antigens to dendritic cells in vivo, bypassing the need for ex vivo cell manipulations. Numerous ongoing studies aim to evaluate the effectiveness of dendritic cell vaccines in preventing tumor relapses and extending patients’ survival. Further implementation of this form of immunotherapy is expected following the identification of the mechanisms controlling dendritic cell immunogenicity, and from a better understanding of the cell dynamics whereby immune responses are orchestrated. Here, we discuss these new insights together with an overview of the dendritic cell-based clinical studies carried out to date.
Alberto Ballestreroa Davide Boya Eva Morana Gabriella Cirmenaa Peter Brossartb Alessio NencioniaEmail:A.Nencioni@gmx.net
[a]Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy;[b]Department of Hematology, Oncology and Immunology, University of Tübingen, D-72076 Tübingen, Germany
OBJECTIVE: To evaluate the effect of infection with bovine respiratory syncytial virus (BRSV) on clearance of inhaled antigens from the lungs of calves. ANIMALS: Eleven 6- to 8-week-old Holstein bull calves. PROCEDURES: Aerosolized (99m)technetium ((99m)Tc)-labeled diethylene triamine pentacetate (DTPA; 3 calves), commonly used to measure integrity of the pulmonary epithelium, and (99m)Tc-labeled ovalbumin (OA; 8 calves), commonly used as a prototype allergen, were used to evaluate pulmonary clearance before, during, and after experimentally induced infection with BRSV or sham inoculation with BRSV. Uptake in plasma (6 calves) and lung-efferent lymph (1 calf) was examined. RESULTS: Clearance of (99m)Tc-DTPA was significantly increased during BRSV infection; clearance of (99m)Tc-OA was decreased on day 7 after inoculation. Clearance time was correlated with severity of clinical disease, and amounts of (99m)Tc-OA in plasma and lymph were inversely correlated with clearance time. Minimum amounts of (99m)Tc-OA were detected at time points when pulmonary clearance of (99m)Tc-OA was most delayed. CONCLUSIONS AND CLINICAL RELEVANCE: BRSV caused infection of the respiratory tract with peak signs of clinical disease at 7 or 8 days after inoculation. Concurrently, there was a diminished ability to move inhaled protein antigen out of the lungs. Prolonged exposure to inhaled antigens during BRSV infection may enhance antigen presentation with consequent allergic sensitization and development of chronic inflammatory lung disease. IMPACT FOR HUMAN MEDICINE: Infection of humans with respiratory syncytial virus early after birth is associated with subsequent development of allergic asthma. Results for BRSV infection in these calves suggested a supportive mechanism for this scenario.
Gershwin LJGunther RAHornof WJLarson RF
Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Gene modification of cells prior to their transplantation, especially stem cells, enhances their survival and increases their function in cell therapy. Like the Trojan horse, the gene-modified cell has to gain entrance inside the host’s walls and survive and deliver its transgene products Using cellular, molecular and gene manipulation techniques the transplanted cell can be protected in a hostile environment from immune rejection, inflammation, hypoxia and apoptosis. Genetic engineering to modify cells involves constructing modules of functional gene sequences. They can be simple reporter genes or complex cassettes with gene switches, cell specific promoters and multiple transgenes. We discuss methods to deliver and construct gene cassettes with viral and non-viral delivery, siRNA, and conditional Cre/Lox P. We review the current uses of gene-modified stem cells in cardiovascular disease, diabetes, neurological diseases, (including Parkinson’s, Alzheimer’s and spinal cord injury repair), bone defects, hemophilia, and cancer.
M. Ian PhillipsaEmail:ian_phillips@kgi.edu Yao Liang Tanga
[a]Keck Graduate Institute, Claremont, Ca 91711, USA
OBJECTIVE: To compare penetration of IV administered marbofloxacin in intraocular fluids of healthy and inflamed eyes in rabbits with endotoxin-induced endophthalmitis. ANIMALS: 35 pigmented rabbits. PROCEDURES: Endophthalmitis was induced in the right eye via intravitreal administration of Escherichia coli endotoxin. The left eye was a control eye. After 24 hours, a single dose of marbofloxacin (4 mg/kg, IV) was administered. Groups of rabbits (n = 5/group) were euthanized 0.5, 1, 2, 4, 6, 10, and 18 hours later, and blood and ocular fluids were collected. Marbofloxacin concentrations were determined via reverse-phase high-performance liquid chromatography, and pharmacokinetic analysis of the data was performed with a mono-compartmental model. RESULTS: Mean area under the aqueous concentration-time curve was significantly lower in control eyes (1.64 +/- 0.07 microg*h/mL) than in inflamed eyes (3.31 +/- 0.11 microg*h/mL). Similarly, drug penetration into aqueous humor was 33% and 65% for control eyes and inflamed eyes, respectively. Mean area under the vitreous humor concentration-time curve for control eyes(1.75 +/- 0.05 microg*h/mL) was significantly less than for inflamed eyes (2.39 +/- 0.16 microg*h/mL). In the vitreous humor, corresponding penetrations were 34% and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Penetration of marbofloxacin into the aqueous and vitreous humor after IV administration was significantly enhanced by intraocular inflammation, suggesting a role for this antimicrobial in the prophylaxis or treatment of bacterial endophthalmitis caused by susceptible pathogens.
Regnier ASchneider MConcordet DToutain PL
UMR181 Physiopathologie et Toxicologie Experimentales, INRA, ENVT, Ecole Nationale Veterinaire,Toulouse Cedex 3, France.
Progress in gene therapy has produced promising results that translate experimental research into clinical treatment. Gene modification has been extensively employed in cell transplantation. The main barrier is an effective gene delivery system. Several viral vectors were utilized in end-stage differentiated cells. Recently, successful applications were described with adenovirus-associated vectors. As an alternative, embryonic stem cell- and stem cell-like systems were established for generation of tissue-specified gene-modified cells. Owing to the feasibility for genetic manipulations and the self-renewing potency of these cells they can be used in a way enabling large-scale in vitro production. This approach offers the establishment of in vitro cell culture systems that will deliver sufficient amounts of highly purified, immunoautologous cells suitable for application in regenerative medicine. In this review, the current technology of gene delivery systems to cells is recapitulated and the latest developments for cell transplantation are discussed.
Yi Laia Irina Drobinskayab Eugen Kolossovc Chunguang Chend Thomas LinndEmail:Thomas.linn@innere.med.uni-giessen.de
[a]Department of Molecular Microbiology & Immunology, University of Missouri-Columbia, USA;[b]Institute for Neurophysiology, University of Cologne, Germany;[c]Axiogenesis AG, Cologne, Germany;[d]Medical Clinic and Policlinic 3, Justus Liebig University, Rodthohl 6, 35392 Giessen, Germany