| Effects of weak static magnetic fields on endothelial cells.
February 2, 2010 at 4:47 PM
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| | Effects of weak static magnetic fields on endothelial cells. Bioelectromagnetics. 2010 Jan 29; Authors: Martino CF, Perea H, Hopfner U, Ferguson VL, Wintermantel E Pulsed electromagnetic fields (PEMFs) have been used extensively in bone fracture repairs and wound healing. It is accepted that the induced electric field is the dose metric. The mechanisms of interaction between weak magnetic fields and biological systems present more ambiguity than that of PEMFs since weak electric currents induced by PEMFs are believed to mediate the healing process, which are absent in magnetic fields. The present study examines the response of human umbilical vein endothelial cells to weak static magnetic fields. We investigated proliferation, viability, and the expression of functional parameters such as eNOS, NO, and also gene expression of VEGF under the influence of different doses of weak magnetic fields. Applications of weak magnetic fields in tissue engineering are also discussed. Static magnetic fields may open new venues of research in the field of vascular therapies by promoting endothelial cell growth and by enhancing the healing ! response of the endothelium. Bioelectromagnetics. (c) 2010 Wiley-Liss, Inc. PMID: 20119972 [PubMed - as supplied by publisher] | | |
| Array of amorphous calcium phosphate particles improves cellular activity on a hydrophobic surface.
February 2, 2010 at 4:47 PM
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| | Array of amorphous calcium phosphate particles improves cellular activity on a hydrophobic surface. J Biomed Mater Res B Appl Biomater. 2010 Jan 29; Authors: Kim I, Kim HJ, Kim HM Poor interaction between cells and surfaces, especially hydrophobic surfaces, results in delayed proliferation and increased apoptosis due to low cell adhesion signaling. To improve cell adhesion, hydrophilic array of amorphous calcium phosphate (ACP) was fabricated on a surface. A phosphate-buffered solution containing calcium ions was prepared at low temperature to prevent spontaneous precipitation. Then, the ion solution was heated to generate nuclei of ACP nanoparticles. The ACP nanoparticles adhered to the hydrophobic polystyrene surface forming an array composed of ACP particles. Multiple treatments of these nuclei with fresh CaP ion solutions increased the diameter and decreased the solubility of ACP particles enough to mediate cellular adhesion. The particle density in the array was dependent on the ion concentration of the CaP ion solutions. The ACP array improved a wide variety of activities when osteoblastic MC3T3-E1 cells were cultured on the ACP array! fabricated on a hydrophobic bacteriological dish surface, compared to those cultured without the ACP array in vitro. The use of ACP array resulted in a lower apoptosis and also increased the spreading of cells to form stress fibers and focal contacts. Cells cultured on the ACP array proliferated more than cells cultured on a hydrophobic surface without the ACP array. The ACP array increased the expression of markers of differentiation in osteoblast. These results indicate that an array of ACP can be used as a coating material for enhancing biocompatibility in tissue engineering or biomaterials rather than modifying the surface with organic molecules. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20119940 [PubMed - as supplied by publisher] | | |
| Polysialic acid immobilized on silanized glass surfaces: a test case for its use as a biomaterial for nerve regeneration.
February 2, 2010 at 4:47 PM
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| | Polysialic acid immobilized on silanized glass surfaces: a test case for its use as a biomaterial for nerve regeneration. J Mater Sci Mater Med. 2010 Jan 30; Authors: Steinhaus S, Stark Y, Bruns S, Haile Y, Scheper T, Grothe C, Behrens P The immobilization of polysialic acid (polySia) on glass substrates has been investigated with regard to the applicability of this polysaccharide as a novel, biocompatible and bioresorbable material for tissue engineering, especially with regard to its use in nerve regeneration. PolySia, a homopolymer of alpha-2,8-linked sialic acid, is involved in post-translational modification of the neural cell adhesion molecule (NCAM). The degradation of polySia can be controlled which makes it an interesting material for coating and for scaffold construction in tissue engineering. Here, we describe the immobilization of polySia on glass surfaces via an epoxysilane linker. Whereas glass surfaces will not actually be used in nerve regeneration scaffolds, they provide a simple and efficient means for testing various methods for the investigation of immobilized polySia. The modified surfaces were investigated with contact angle measurements and the quantity of immobilized polySi! a was examined by the thiobarbituric acid assay and a specific polySia-ELISA. The interactions between the polySia-modified surface and immortalized Schwann cells were evaluated via cell adhesion and cell viability assays. The results show that polySia can be immobilized on glass surfaces via the epoxysilane linker and that surface-bound polySia has no toxic effects on Schwann cells. Therefore, as a key substance in the development of vertebrates and as a favourable substrate for the cultivation of Schwann cells, it offers interesting features for the use in nerve guidance tubes for treatment of peripheral nerve injuries. PMID: 20119645 [PubMed - as supplied by publisher] | | |
| Stem Cell Therapy: Pieces of the Puzzle.
February 2, 2010 at 4:47 PM
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| | Stem Cell Therapy: Pieces of the Puzzle. J Cardiovasc Transl Res. 2010 Feb;3(1):49-60 Authors: Schoenhard JA, Hatzopoulos AK Acute ischemic injury and chronic cardiomyopathies can cause irreversible loss of cardiac tissue leading to heart failure. Cellular therapy offers a new paradigm for treatment of heart disease. Stem cell therapies in animal models show that transplantation of various cell preparations improves ventricular function after injury. The first clinical trials in patients produced some encouraging results, despite limited evidence for the long-term survival of transplanted cells. Ongoing research at the bench and the bedside aims to compare sources of donor cells, test methods of cell delivery, improve myocardial homing, bolster cell survival, and promote cardiomyocyte differentiation. This article reviews progress toward these goals. PMID: 20119487 [PubMed - as supplied by publisher] | | |
| Nanoinformatics and DNA-Based Computing: Catalyzing Nanomedicine.
February 2, 2010 at 4:47 PM
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| | Nanoinformatics and DNA-Based Computing: Catalyzing Nanomedicine. Pediatr Res. 2010 Jan 28; Authors: Maojo V, Martin-Sanchez F, Kulikowski C, Rodriguez-Paton A, Fritts M Five decades of research and practical application of computers in biomedicine has given rise to the discipline of medical informatics, which has made many advances in genomic and translational medicine possible. Developments in nanotechnology are opening up the prospects for nanomedicine and regenerative medicine where informatics and DNA computing can become the catalysts enabling health care applications at sub-molecular or atomic scales. While nanomedicine promises a new exciting frontier for clinical practice and biomedical research, issues involving cost-effectiveness studies, clinical trials and toxicity assays, drug delivery methods, and the implementation of new personalized therapies still remain challenging. Nanoinformatics can accelerate the introduction of nano-related research and applications into clinical practice, leading to an area that could be called "translational nanoinformatics". At the same time, DNA and RNA computing presents an entirely n! ovel paradigm for computation. Nanoinformatics and DNA-based computing are together likely to completely change the way we model and process information in biomedicine and impact the emerging field of nanomedicine most strongly. In this paper we review work in nanoinformatics and DNA (and RNA)-based computing, including applications into nanopediatrics. We analyse their scientific foundations, current research and projects, envisioned applications and potential problems that might arise from them. PMID: 20118825 [PubMed - as supplied by publisher] | | |
| New concepts in cardiac stem cell therapy.
February 2, 2010 at 4:47 PM
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| | New concepts in cardiac stem cell therapy. Hellenic J Cardiol. 2010 Jan-Feb;51(1):10-4 Authors: Wojakowski W, Tendera M PMID: 20118038 [PubMed - in process] | | |
| The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering.
February 2, 2010 at 4:47 PM
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| | The incorporation of strontium and zinc into a calcium-silicon ceramic for bone tissue engineering. Biomaterials. 2010 Jan 29; Authors: Zreiqat H, Ramaswamy Y, Wu C, Paschalidis A, Lu Z, James B, Birke O, McDonald M, Little D, Dunstan CR In this study we developed novel scaffolds through the controlled substitution and incorporation of strontium and zinc into a calcium-silicon system to form Sr-Hardystonite (Sr-Ca(2)ZnSi(2)O(7), Sr-HT). The physical and biological properties of Sr-HT were compared to Hardystonite (Ca(2)ZnSi(2)O(7)) [HT]. We showed that Sr-HT scaffolds are porous with interconnected porous network (interconnectivity: 99%) and large pore size (300-500mum) and an overall porosity of 78%, combined with a relatively high compressive strength (2.16+/-0.52MPa). These properties are essential for enhancing bone ingrowth in load-bearing applications. Sr-HT ceramic scaffolds induced the attachment and differentiation of human bone derived cells (HOB), compared to that for the HT scaffolds. Sr-HT scaffolds enhanced expression of alkaline phosphatase, Runx-2, osteopontin, osteocalcin and bone sialoprotein. The in vivo osteoconductivity of the scaffolds was assessed at 3 and 6 weeks following ! implantation in tibial bone defects in rats. Histological staining revealed rapid new growth of bone into the pores of the 3D scaffolds with the Sr-HT and HT, relative to the beta-tricalcium phosphate (beta-TCP). In vivo, HT and Sr-HT produced distinct differences in the patterns of degradation of the materials, and their association with TRAP positive osteoclast-like cells with HT appearing more resistant compared to both Sr-HT and beta-TCP. PMID: 20117832 [PubMed - as supplied by publisher] | | |
| Endoscopic Versus Open Carpal Tunnel Release.
February 2, 2010 at 4:47 PM
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| | Endoscopic Versus Open Carpal Tunnel Release. Arthroscopy. 2010 Jan;26(1):26-33 Authors: Vasiliadis HS, Xenakis TA, Mitsionis G, Paschos N, Georgoulis A PURPOSE: This study compared endoscopic carpal tunnel release with the conventional open technique with respect to short- and long-term improvements in functional and clinical outcomes. METHODS: We assessed 72 outpatients diagnosed with carpal tunnel syndrome. Of these patients, 37 underwent the endoscopic method according to Chow and 35 were assigned to the open method. Improvement in symptoms, severity, and functionality were evaluated at 2 days, 1 week, 2 weeks, and 1 year postoperatively. Changes in clinical outcomes were evaluated at 1 year postoperatively. Complications were also assessed. RESULTS: Both groups showed similar improvement in all but 1 outcome 1 year after the release; increase in grip strength was significantly higher in the endoscopic group. However, the endoscopic method showed a greater improvement in symptoms and functional status compared with the open method at 2 days, 1 week, and 2 weeks postoperatively. Separate analysis of the questio! ns referring to pain showed that the delay in improvement in the open group was because of the persistence of pain for a longer period. Paresthesias and numbness decrease immediately after the operation with comparable rates for both groups. CONCLUSIONS: Endoscopic carpal tunnel release provides a faster recovery to operated patients for the first 2 weeks, with faster relief of pain and faster improvement in functional abilities. Paresthesia and numbness subside in an identical manner with the 2 techniques. At 1 year postoperatively, both open and endoscopic techniques seem to be equivalently efficient. LEVEL OF EVIDENCE: Level II, prospective comparative study. PMID: 20117624 [PubMed - as supplied by publisher] | | |
| The fate of an endothelium layer after preconditioning.
February 2, 2010 at 4:47 PM
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| | The fate of an endothelium layer after preconditioning. J Vasc Surg. 2010 Jan;51(1):174-183 Authors: Yazdani SK, Tillman BW, Berry JL, Soker S, Geary RL BACKGROUND: A strategy in minimizing thrombotic events of vascular constructs is to seed the luminal surface with autologous endothelial cells (ECs). The task of seeding ECs can be achieved via bioreactors, which induce mechanical forces (shear stress, strain, pressure) onto the ECs. Although bioreactors can achieve a confluent layer of ECs in vitro, their acute response to blood remains unclear. Moreover, the necessary mechanical conditions that will increase EC adhesion and function remain unclear. We hypothesize that preconditioning seeded endothelium under physiological flow will enhance their retention and function. OBJECTIVE: To determine the role of varying preconditioning protocols on seeded ECs in vitro and in vivo. METHODS: Scaffolds derived from decelluarized arteries seeded with autologous ECs were preconditioned for 9 days. Three specific protocols, low steady shear stress (SS), high SS, and cyclic SS were investigated. After preconditioning, the seed! ed grafts were exposed to 15 minutes of blood via an ex vivo arteriovenous shunt model or alternately an in vivo arteriovenous bypass graft model. RESULTS: The shunt model demonstrated ECs remained intact for all conditions. In the arteriovenous bypass model, only the cyclic preconditioned grafts remained intact, maintained morphology, and resisted the attachment of circulating blood elements such as platelets, red blood cells, and leukocytes. Western blotting analysis demonstrated an increase in the protein expression of eNOS and prostaglandin I synthase for the cyclic high shear stress-conditioned cells relative to cells conditioned with high shear stress alone. CONCLUSION: Cyclic preconditioning has been shown here to increase the ECs ability to resist blood flow-induced shear stress and the attachment of circulating blood elements, key attributes in minimizing thrombotic events. These studies may ultimately establish protocols for the formation of a more durable endothe! lial monolayer that may be useful in the context of small vess! el arter ial reconstruction. PMID: 20117500 [PubMed - as supplied by publisher] | | |
| Growth Differentiation Factor 5 Regulates Cardiac Repair After Myocardial Infarction.
February 2, 2010 at 4:47 PM
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| | Growth Differentiation Factor 5 Regulates Cardiac Repair After Myocardial Infarction. J Am Coll Cardiol. 2010 Jan 12;55(2):135-143 Authors: Zaidi SH, Huang Q, Momen A, Riazi A, Husain M OBJECTIVES: The aim of this study was to examine the function of the bone morphogenic protein growth differentiation factor 5 (Gdf5) in a mouse model of myocardial infarction (MI). BACKGROUND: The Gdf5 has been implicated in skeletal development, but a potential role in the heart had not been studied. METHODS: The Gdf5-knockout (KO) and wild-type (WT) mice were subjected to permanent left anterior descending coronary artery (LAD) ligation. Cardiac pathology, function, gene expression levels, and signaling pathways downstream of Gdf5 were examined. Effects of recombinant Gdf5 (rGdf5) were tested in primary cardiac cell cultures. RESULTS: The WT mice showed increased cardiac Gdf5 levels after MI, with increased expression in peri-infarct cardiomyocytes and myofibroblasts. At 1 and 7 days after MI, no differences were observed in ischemic or infarct areas between WT and Gdf5-KO mice. However, by 28 days after MI, Gdf5-KO mice exhibited increased infarct scar expansio! n and thinning with decreased arteriolar density compared with WT. The Gdf5-KO hearts also displayed increased left ventricular dilation, with decreased contractility after MI. At 4 days after MI, Gdf5-KO mice exhibited increased cardiomyocyte apoptosis and decreased expression of anti-apoptotic genes Bcl2 and Bcl-xL compared with WT. Unexpectedly, Gdf5-KO hearts displayed increased Smad 1/5/8 phosphorylation but decreased p38-mitogen-activated protein kinase (MAPK) phosphorylation versus WT. The latter was associated with increased collagen gene (Col1a1, Col3a1) expression and fibrosis. In cultures, rGdf5 induced p38-MAPK phosphorylation in cardiac fibroblasts and Smad-dependent increases in Bcl2 and Bcl-xL in cardiomyocytes. CONCLUSIONS: Increased expression of Gdf5 after MI limits infarct scar expansion in vivo. These effects might be mediated by Gdf5-induced p38-MAPK signaling in fibroblasts and Gdf5-driven Smad-dependent pro-survival signaling in cardiomyocytes. PMID: 20117381 [PubMed - as supplied by publisher] | | |
| Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis.
February 2, 2010 at 4:47 PM
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| | Selection of optimal passage of bone marrow-derived mesenchymal stem cells for stem cell therapy in patients with amyotrophic lateral sclerosis. Neurosci Lett. 2010 Jan 28; Authors: Choi MR, Kim HY, Park JY, Lee TY, Baik CS, Chai YG, Jung KH, Park KS, Roh W, Kim KS, Kim SH Mesenchymal stem cells (MSCs) obtained from bone marrow (BM) are currently used as an alternative therapy in amyotrophic lateral sclerosis (ALS) patients. Selection of optimal passages of autologous BM-derived MSCs during long-term in vitro expansion is important for clinical trials in patients with ALS. We isolated and expanded MSCs from the BM of eight ALS patients to analyze the growth kinetics, differentiation potential, cellular surface antigen expression, karyotype modifications and secretion of various cytokines during long-term culture. The morphology and size of the cells changed from small and spindle-like cells to large and polygonal types in later passages. The growth rate of the MSCs was highest in the third passage, followed by a gradual decrease. There were no special modifications of cell surface antigens or the karyotype of the MSCs from the first to the tenth passage. MSCs in the fourth passage were differentiated into adipocytes, osteocytes and ! chondrocytes. When we analyzed the cultured media of MSCs at the third, fifth, seventh and ninth passages, IL-6, VEGF and IL-8 showed high expression, with more than 50pg/10,000 cells at these passages; however, their expression progressively decreased with additional passages. In addition, secretion of IL-15, GM-CSF, IL-10, PDGF bb, G-CSF, IL-1beta, basic FGF and IFN-gamma gradually decreased over prolonged culture. We suggest that MSCs at earlier passages are more suitable for stem cell therapy in ALS patients because of their stability and more potent anti-inflammatory and neuroprotective properties. PMID: 20117176 [PubMed - as supplied by publisher] | | |
| Carbohydrate engineered cells for regenerative medicine.
February 2, 2010 at 4:47 PM
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| | Carbohydrate engineered cells for regenerative medicine. Adv Drug Deliv Rev. 2010 Jan 28; Authors: Du J, Yarema KJ Carbohydrates are integral components of the stem cell niche on several levels; proteoglycans are a major constituent of the extracellular matrix (ECM) surrounding a cell, glycosoaminoglycans (GAGs) help link cells to the ECM and the neighboring cells, and small but informationally-rich oligosaccharides provide a "sugar code" that identifies each cell and provides it with unique functions. This article samples roles that glycans play in development and then describes how metabolic glycoengineering - a technique where monosaccharide analogs are introduced into the metabolic pathways of a cell and are biosynthetically incorporated into the glycocalyx - is overcoming many of the long-standing barriers to manipulating carbohydrates in living cells and tissues and is becoming an intriguing new tool for tissue engineering and regenerative medicine. PMID: 20117158 [PubMed - as supplied by publisher] | | |
| Mechanical behavior of human mesenchymal stem cells during adipogenic and osteogenic differentiation.
February 2, 2010 at 4:47 PM
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| | Mechanical behavior of human mesenchymal stem cells during adipogenic and osteogenic differentiation. Biochem Biophys Res Commun. 2010 Jan 28; Authors: Yu H, Tay CY, Leong WS, Tan SC, Liao K, Tan LP Human mesenchymal stem cells (hMSCs) have gained widespread attention in the field of tissue engineering but not much is known about the changes of mechanical properties during the process of cell lineage commitment and the mechanisms of these behaviors. It is believed that exploring the inter-relations between stem cells mechanical properties and lineage commitment will shed light on the mechanobiology aspect of differentiation. hMSCs were cultured in adipogenic and osteogenic mediums and the elastic moduli were monitored using micropipette aspiration. It was found that hMSCs undergoing osteogenesis have an instantaneous Young's modulus of 890+/-219 Pa and an equilibrium Young's modulus of 224+/-40 Pa, each is about 2 fold higher than the control group. Interestingly, cells cultured in adipogenic medium exhibited a slight increase in the cellular modulus followed by a decrease relative to that of the control group. Gene expression study was employed to gain insig! hts into this phenomenon. Concomitant up regulation of actin binding filamin A (FLNa) and gamma-Tubulin with the cellular elastic modulus indicated their important role in mechanical regulation during hMSCs differentiation. Statistical results showed that cell shape and cell area changed with cellular mechanical properties, which means that cell morphology has a close relation with cell elastic modulus in the initial stage of differentiation. Collectively, these results provide a quantitative description of hMSCs mechanical behavior during the process of differentiation as well as the possible accompanying mechanism at the biomolecular level. PMID: 20117089 [PubMed - as supplied by publisher] | | |
| [Principles of the local treatment: Surgical processing.]
February 2, 2010 at 4:47 PM
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| | [Principles of the local treatment: Surgical processing.] Pathol Biol (Paris). 2010 Jan 28; Authors: Chaouat M, Zakine G, Mimoun M The deep burns require a surgical treatment. The third degree circular burns require escharotomies and sometimes fasciotomies to avoid vascular compression. Early burn wound excision permits to remove the necrotic tissue that produce toxins and encourage infection. Wound coverage by an autologous split-thickness skin grafting, meshed or not, usually leads to a correct scare quality. In severe burns, when donor's sites are limited, the homografts permit to pass a cape even though they are rejected secondarily. The keratinocytes culture remains a difficult and exceptional technique for very severe burns permitting to save their life but with poor cosmetic results. Artificial dermal substitute could sometimes permit to replace the homograft and to improve the cosmetic results of the grafts by a better reconstitution of skin. If early burn wound excision with autologous split-thickness skin grafting remains the gold standard, the tissue-engineering will be a future wa! y for the surgical treatment of the burns. PMID: 20116939 [PubMed - as supplied by publisher] | | |
| Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran-hyaluronic acid conjugates for cartilage tissue engineering.
February 2, 2010 at 4:47 PM
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| | Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran-hyaluronic acid conjugates for cartilage tissue engineering. Biomaterials. 2010 Jan 28; Authors: Jin R, Moreira Teixeira LS, Dijkstra PJ, van Blitterswijk CA, Karperien M, Feijen J Polysaccharide hybrids consisting of hyaluronic acid (HA) grafted with a dextran-tyramine conjugate (Dex-TA) were synthesized and investigated as injectable biomimetic hydrogels for cartilage tissue engineering. The design of these hybrids (denoted as HA-g-Dex-TA) is based on the molecular structure of proteoglycans present in the extracellular matrix of native cartilage. Hydrogels of HA-g-Dex-TA were rapidly formed within 2 min via enzymatic crosslinking of the tyramine residues in the presence of horseradish peroxidase and hydrogen peroxide. The gelation time, equilibrium swelling and storage modulus could be adjusted by varying the degree of substitution of tyramine residues and polymer concentration. Bovine chondrocytes incorporated in the HA-g-Dex-TA hydrogels remained viable, as shown by the Live-dead assay. Moreover, enhanced chondrocyte proliferation and matrix production were observed in the HA-g-Dex-TA hydrogels compared to Dex-TA hydrogels. These result! s suggest that HA-g-Dex-TA hydrogels have a high potential as injectable scaffolds for cartilage tissue engineering. PMID: 20116847 [PubMed - as supplied by publisher] | | |
| Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation.
February 2, 2010 at 4:47 PM
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| | Timing of captopril administration determines radiation protection or radiation sensitization in a murine model of total body irradiation. Exp Hematol. 2010 Jan 27; Authors: Davis TA, Landauer MR, Mog SR, Barshishat-Kupper M, Zins SR, Amare MF, Day RM OBJECTIVE: Angiotensin II (Ang II), a potent vasoconstrictor, affects the growth and development of hematopoietic cells. Mixed findings have been reported for the effects of ACE inhibitors on radiation-induced injury to the hematopoietic system. We investigated the consequences of different regimens of the ACE inhibitor captopril on radiation-induced hematopoietic injury. METHODS: C57BL/6 mice were either sham irradiated or were exposed to (60)Co total body irradiation (0.6 Gy/min). Captopril was provided in the water for different time periods relative to irradiation. RESULTS: In untreated mice, the survival rate from 7.5 Gy was 50% at 30 days postirradiation. Captopril treatment for 7 days prior to irradiation resulted in radiosensitization with 100% lethality and a rapid decline of mature blood cells. In contrast, captopril treatment beginning 1 hour postirradiation and continuing for 30 days resulted in 100% survival, with improved recovery of mature blood cel! ls and multilineage hematopoietic progenitors. In nonirradiated control mice captopril biphasically modulated Lin(-) marrow progenitor cell cycling. After 2 days, captopril suppressed G(0)-G(1) transition and a greater number of cells entered a quiescent state. However, after 7 days of captopril treatment Lin(-) progenitor cell cycling increased compared to untreated control mice. CONCLUSION: These findings suggest that ACE inhibition affects hematopoietic recovery following radiation by modulating the hematopoietic progenitor cell cycle. The timing of captopril treatment relative to radiation exposure differentially affects the viability and repopulation capacity of spared hematopoietic stem cells and therefore can result in either radiation protection or radiation sensitization. PMID: 20116413 [PubMed - as supplied by publisher] | | |
| Exogenous Expression of HIF-1alpha Promotes Cardiac Differentiation of Embryonic Stem Cells.
February 2, 2010 at 4:47 PM
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| | Exogenous Expression of HIF-1alpha Promotes Cardiac Differentiation of Embryonic Stem Cells. J Mol Cell Cardiol. 2010 Jan 27; Authors: Ng KM, Lee YK, Chan YC, Lai WH, Fung ML, Li RA, Siu CW, Tse HF Hypoxia plays an important role in the proliferation, differentiation and maintenance of the cardiovascular system during development. While low oxygen tension appears to direct the cultured embryonic stem cells (ESCs) to differentiate into cardiomyocytes, the underlying molecular mechanism remains unclear. At a molecular level, hypoxia inducible factor-1 (HIF-1) plays an important role in handling the hypoxia signal. In the present study, we demonstrated that expression of exogenous HIF-1alpha cDNA into murine ESCs significantly promoted cardiogenesis as indicated by a higher percentage of beating embryoid body and troponin-T positive cell counts as well as increased expression of early and late cardiac markers, such as GATA-binding protein 4 & 6, NK2 transcription factor related locus 5, alpha-myosin heavy chain, beta-myosin heavy chain and myosin light chain 2 ventricular transcripts. In addition, the transducer cells exhibited increased mRNA levels of card! iotrophin-1 and vascular endothelial growth factor, along with phosphorylation of eNOS [p-eNOS (ser1171)]. Application of NOS inhibitors, diphenyleneiodonium chloride (DPI), N(omega)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) or N(omega)-Nitro-L-arginine (L-NNA) abolished the HIF-1alpha stimulated cardiac differentiation. With the clues of up-regulated mRNA expression of calcium handling proteins, ryanodine receptor 2, sodium calcium exchanger and sarcoplasmic/endoplasmic reticulum calcium ATPase, in the transduced HIF-1alpha ESCs, further study indicated that the maximum upstroke and decay velocity was significantly increased in both non-caffeine and caffeine-induced calcium transient in ESCs-derived cardiomyocytes. This suggests a well developed function of the sarcoplasmic reticulum in ESC-dervied cardiomyocytes. Electrophysiological study also indicated that a portion of the HIF-1alpha transduced cells exhibited prominent phase-4 depolarization. These findings! suggest that ken activation of the HIF-1 pathway enhances dif! ferentia tion and maturation of cardiomyocytes derived from ESCs. PMID: 20116384 [PubMed - as supplied by publisher] | | |
| Polyblend nanofibers for biomedical applications: perspectives and challenges.
February 2, 2010 at 4:47 PM
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| | Polyblend nanofibers for biomedical applications: perspectives and challenges. Trends Biotechnol. 2010 Jan 28; Authors: Gunn J, Zhang M Advances in disease treatment and tissue regeneration are buoyed by new, multifaceted materials that emulate and coercively interact with the local microenvironment. Polyblend nanofibers represent an emerging class of biomimetic nanostructures that can act as proxies of the native tissue, while providing topographical and biochemical cues that promote healing. These fibers are prepared with mixtures of synthetically and naturally derived polymers that can behave cooperatively to demonstrate unique combinations of mechanical, biochemical and structural properties. This flexibility has led to the application of polyblend nanofibers in a wide assortment of tissue engineering and drug delivery systems. In this review, we will examine design criteria and properties of polymer-blend nanofibers and their use in tissue engineering and local therapeutic delivery applications. PMID: 20116113 [PubMed - as supplied by publisher] | | |
| Genetically modified cells in regenerative medicine and tissue engineering.
February 2, 2010 at 4:47 PM
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| | Genetically modified cells in regenerative medicine and tissue engineering. Adv Drug Deliv Rev. 2010 Jan 26; Authors: Sheyn D, Mizrahi O, Benjamin S, Pelled G, Gazit D Regenerative medicine appears to take as its patron, the Titan Prometheus, whose liver was able to regenerate daily, as the field attempts to restore lost, damaged, or aging cells and tissues. The tremendous technological progress achieved during the last decade in gene transfer methods and imaging techniques, as well as recent increases in our knowledge of cell biology, have opened new horizons in the field of regenerative medicine. Genetically engineered cells are a tool for tissue engineering and regenerative medicine, albeit a tool whose development is fraught with difficulties. Gene-and-cell therapy offers solutions to severe problems faced by modern medicine, but several impediments obstruct the path of such treatments as they move from the laboratory toward the clinical setting. In this review we provide an overview of recent advances in the gene-and-cell therapy approach and discuss the main hurdles and bottlenecks of this approach on its path to clinical ! trials and prospective clinical practice. PMID: 20114067 [PubMed - as supplied by publisher] | | |
| Design and validation of a novel bioreactor principle to combine online micro-computed tomography monitoring and mechanical loading in bone tissue engineering.
February 2, 2010 at 4:47 PM
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| | Design and validation of a novel bioreactor principle to combine online micro-computed tomography monitoring and mechanical loading in bone tissue engineering. Rev Sci Instrum. 2010 Jan;81(1):014303 Authors: Hagenmüller H, Hitz M, Merkle HP, Meinel L, Müller R Mechanical loading plays an important role in bone remodeling in vivo and, therefore, has been suggested as a key parameter in stem cell-based engineering of bone-like tissue in vitro. However, the optimization of loading protocols during stem cell differentiation and subsequent bone-like tissue formation is challenged by multiple input factors, which are difficult to control and validate. These include the variable cellular performance of cells harvested from different patients, nonstandardized culture media components, the choice of the biomaterial forming the scaffold, and its morphology, impacting a broader validity of mechanical stimulation regimens. To standardize the cell culture of bone-like tissue constructs, we suggest the involvement of time-lapsed feedback loops. For this purpose we present a prototype bioreactor that combines online, nondestructive monitoring using micro-computed tomography and direct mechanical loading of three-dimensional tissue eng! ineering constructs. Validation of this system showed displacement steps down to 1 mum and cyclic sinusoidal loadings of up to 10 Hz. Load detection resolution was 0.01 N, and micro-computed tomography data were of high quality. For the first time, the developed bioreactor links time-lapsed, nondestructive, and dynamic imaging with mechanical stimulation, designed for cell culture under sterile conditions. This system is believed to substantially improve today's experimental options to study and optimize osteogenic stem cell culture and differentiation at the interface with mechanical stimulation. PMID: 20113118 [PubMed - in process] | | |
| Enhanced Cell Ingrowth and Proliferation through Three-Dimensional Nanocomposite Scaffolds with Controlled Pore Structures.
February 2, 2010 at 4:47 PM
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| | Enhanced Cell Ingrowth and Proliferation through Three-Dimensional Nanocomposite Scaffolds with Controlled Pore Structures. Biomacromolecules. 2010 Jan 29; Authors: Lee KW, Wang S, Yaszemski MJ, Lu L We present enhanced cell ingrowth and proliferation through cross-linked three-dimensional (3D) nanocomposite scaffolds fabricated using poly(propylene fumarate) (PPF) and hydroxyapatite (HA) nanoparticles. Scaffolds with controlled internal pore structures were produced from computer-aided design (CAD) models and solid freeform fabrication (SFF) technique, while those with random pore structures were fabricated by a NaCl leaching technique for comparison. The morphology and mechanical properties of scaffolds were characterized using scanning electron microscopy (SEM) and mechanical testing, respectively. Pore interconnectivity of scaffolds was assessed using X-ray microcomputed tomography (micro-CT) and 3D imaging analysis. In vitro cell studies have been performed using MC3T3-E1 mouse preosteoblasts and cultured scaffolds in a rotating-wall-vessel bioreactor for 4 and 7 days to assess cell attachment, viability, ingrowth depth, and proliferation. The mechanical ! properties of cross-linked nanocomposite scaffolds were not significantly different after adding HA or varying pore structures. However, pore interconnectivity of PPF/HA nanocomposite scaffolds with controlled pore structures has been significantly increased, resulting in enhanced cell ingrowth depth 7 days after cell seeding. Cell attachment and proliferation are also higher in PPF/HA nanocomposite scaffolds. These results suggest that cross-linked PPF/HA nanocomposite scaffolds with controlled pore structures may lead to promising bone tissue engineering scaffolds with excellent cell proliferation and ingrowth. PMID: 20112899 [PubMed - as supplied by publisher] | | |
| [Progress in researches on stem cell therapy for erectile dysfunction]
February 2, 2010 at 4:47 PM
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| | [Progress in researches on stem cell therapy for erectile dysfunction] Zhonghua Nan Ke Xue. 2009 Oct;15(10):937-40 Authors: Jiang YB, Gou X Erectile dysfunction (ED) commonly results from endothelial dysfunction and erectile nerve damage. Recent researches have focused on the preclinical studies of stem cell-based therapies targeted at repairing penile endothelium and protecting erectile nerves. Early studies showed that stem cell- or gene-modified stem cell-based therapies may have enduring efficacy and eventually lead to a cure for ED. Such stem cells as embryonic, mesenchymal, muscle-derived and adipose-derived ones and endothelial progenitor cells all have differentiation potentials and obvious advantages in protecting and repairing both nervi erigentes and corpus cavernosum vascular endothelial cells. Stem cell-based therapies promise to be an effective approach to human erectile dysfunction. PMID: 20112746 [PubMed - in process] | | |
| Craniofacial tissue regeneration: where are we?
February 2, 2010 at 4:47 PM
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| | Craniofacial tissue regeneration: where are we? J Calif Dent Assoc. 2009 Nov;37(11):799-803 Authors: Bhatt A, Le Anh D This paper provides a brief review of adult stem cells and their potential clinical applications, specifically in craniofacial regeneration. The initial discovery of stem cells from a variety of tissues has infused tremendous research, and, in conjunction with bioengineering technologies, has potential to transform clinical dentistry. PMID: 19998656 [PubMed - indexed for MEDLINE] | | |
| Living skin equivalents constructed using human amnions as a matrix.
February 2, 2010 at 4:47 PM
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| | Living skin equivalents constructed using human amnions as a matrix. J Dermatol Sci. 2009 Dec;56(3):188-95 Authors: Yang L, Shirakata Y, Tokumaru S, Xiuju D, Tohyama M, Hanakawa Y, Hirakawa S, Sayama K, Hashimoto K BACKGROUND: Living skin equivalents (LSEs) are being used to treat burn wounds, skin defects, and chronic wounds, and today, several biomaterials are applied as dermal matrices in LSEs. The amnionic membrane (AM) is known to have useful properties as a dermal matrix and can be used to construct a LSE. OBJECTIVE: To develop a new LSE with human AM as the matrix. METHODS: Human AM was de-epithelialized and investigated to determine whether it supported keratinocyte adherence and proliferation, and fibroblast in-growth and proliferation. A new LSE was constructed by seeding keratinocytes on the epithelial side of fibroblast-populated, de-epithelialized AM and was investigated histologically. The LSE was transplanted onto a full-thickness wound on a nude mouse and a histological examination was conducted. RESULTS: De-epithelialized AM supported the adherence and proliferation of keratinocytes and the in-growth of fibroblasts. The new LSE demonstrated good mechanical p! roperties and revealed good morphology, with a well differentiated epidermis and well developed basement membrane. The LSE grafts survived well on nude mice, showing good morphology. CONCLUSION: A LSE with amnions as a matrix exhibited good morphology, low cost, and good mechanical properties and may be useful as a skin substitute for clinical use. PMID: 19853413 [PubMed - indexed for MEDLINE] | | |
| RalA suppresses early stages of Ras-induced squamous cell carcinoma progression.
February 2, 2010 at 4:47 PM
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| | RalA suppresses early stages of Ras-induced squamous cell carcinoma progression. Oncogene. 2010 Jan 7;29(1):45-55 Authors: Sowalsky AG, Alt-Holland A, Shamis Y, Garlick JA, Feig LA Ras proteins activate Raf and PI-3 kinases, as well as exchange factors for RalA and RalB GTPases. Many previous studies have reported that the Ral-signaling cascade contributes positively to Ras-mediated oncogenesis. Here, using a bioengineered tissue model of early steps in Ras-induced human squamous cell carcinoma of the skin, we found the opposite. Conversion of Ras-expressing keratinocytes from a premalignant to malignant state induced by decreasing E-cadherin function was associated with and required an approximately two to threefold decrease in RalA expression. Moreover, direct knockdown of RalA to a similar degree by shRNA expression in these cells reduced E-cadherin levels and also induced progression to a malignant phenotype. Knockdown of the Ral effector, Exo84, mimicked the effects of decreasing RalA levels in these engineered tissues. These phenomena can be explained by our finding that the stability of E-cadherin in Ras-expressing keratinocytes depen! ds upon this RalA signaling cascade. These results imply that an important component of the early stages in squamous carcinoma progression may be a modest decrease in RalA gene expression that magnifies the effects of decreased E-cadherin expression by promoting its degradation. PMID: 19802010 [PubMed - indexed for MEDLINE] | | |
| Enhanced generation of induced pluripotent stem cells from a subpopulation of human fibroblasts.
February 2, 2010 at 4:47 PM
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| | Enhanced generation of induced pluripotent stem cells from a subpopulation of human fibroblasts. PLoS One. 2009;4(9):e7118 Authors: Byrne JA, Nguyen HN, Reijo Pera RA BACKGROUND: The derivation of induced pluripotent stem cells (iPSCs) provides new possibilities for basic research and novel cell-based therapies. Limitations, however, include our current lack of understanding regarding the underlying mechanisms and the inefficiency of reprogramming. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report identification and isolation of a subpopulation of human dermal fibroblasts that express the pluripotency marker stage specific embryonic antigen 3 (SSEA3). Fibroblasts that expressed SSEA3 demonstrated an enhanced iPSC generation efficiency, while no iPSC derivation was obtained from the fibroblasts that did not express SSEA3. Transcriptional analysis revealed NANOG expression was significantly increased in the SSEA3 expressing fibroblasts, suggesting a possible mechanistic explanation for the differential reprogramming. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this study is the first to identify a pluripotency marker in a heterogen! eous population of human dermal fibroblasts, to isolate a subpopulation of cells that have a significantly increased propensity to reprogram to pluripotency and to identify a possible mechanism to explain this differential reprogramming. This discovery provides a method to significantly increase the efficiency of reprogramming, enhancing the feasibility of the potential applications based on this technology, and a tool for basic research studies to understand the underlying reprogramming mechanisms. PMID: 19774082 [PubMed - indexed for MEDLINE] | | |
| Up-regulation of oligodendrocyte precursor cell alphaV integrin and its extracellular ligands during central nervous system remyelination.
February 2, 2010 at 4:47 PM
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| | Up-regulation of oligodendrocyte precursor cell alphaV integrin and its extracellular ligands during central nervous system remyelination. J Neurosci Res. 2009 Nov 15;87(15):3447-55 Authors: Zhao C, Fancy SP, Franklin RJ, ffrench-Constant C To determine the role of extracellular matrix molecules and their integrin ligands in CNS remyelination, we have examined in experimentally induced focal demyelinated lesions the expression of the two classes of integrins implicated in oligodendrocyte development and myelination: alpha6 laminin-binding integrins and alphaV integrins that bind a range of extracellular matrix proteins containing the -Arg-Gly-Asp- (RGD) recognition sequence. Only alphaV integrins were up-regulated during remyelination, being expressed on oligodendrocyte precursor cells during their recruitment into the lesion. Next, therefore, we examined the expression of extracellular matrix ligands for alphaV integrins and documented increased expression of tenascin-C, tenascin-R, fibronectin, and vitronectin. Taken together with our previous discovery of high levels of expression of another alphaV ligand, osteopontin, during remyelination in these lesions, our findings suggest that alphaV integri! ns make an important contribution to successful repair in the CNS. PMID: 19739252 [PubMed - indexed for MEDLINE] | | |
| Signaling pathways controlling pluripotency and early cell fate decisions of human induced pluripotent stem cells.
February 2, 2010 at 4:47 PM
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| | Signaling pathways controlling pluripotency and early cell fate decisions of human induced pluripotent stem cells. Stem Cells. 2009 Nov;27(11):2655-66 Authors: Vallier L, Touboul T, Brown S, Cho C, Bilican B, Alexander M, Cedervall J, Chandran S, Ahrlund-Richter L, Weber A, Pedersen RA Human pluripotent stem cells from embryonic origins and those generated from reprogrammed somatic cells share many characteristics, including indefinite proliferation and a sustained capacity to differentiate into a wide variety of cell types. However, it remains to be demonstrated whether both cell types rely on similar mechanisms to maintain their pluripotent status and to control their differentiation. Any differences in such mechanisms would suggest that reprogramming of fibroblasts to generate induced pluripotent stem cells (iPSCs) results in novel states of pluripotency. In that event, current methods for expanding and differentiating human embryonic stem cells (ESCs) might not be directly applicable to human iPSCs. However, we show here that human iPSCs rely on activin/nodal signaling to control Nanog expression and thereby maintain pluripotency, thus revealing their mechanistic similarity to human ESCs. We also show that growth factors necessary and suffic! ient for achieving specification of human ESCs into extraembryonic tissues, neuroectoderm, and mesendoderm also drive differentiation of human iPSCs into the same tissues. Importantly, these experiments were performed in fully chemically defined medium devoid of factors that could obscure analysis of developmental mechanisms or render the resulting tissues incompatible with future clinical applications. Together these data reveal that human iPSCs rely on mechanisms similar to human ESCs to maintain their pluripotency and to control their differentiation, showing that these pluripotent cell types are functionally equivalent. PMID: 19688839 [PubMed - indexed for MEDLINE] | | |
| Isoniazid in patient plasma may cause a false-positive result on the complement-dependent cytotoxicity test.
February 2, 2010 at 4:47 PM
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| | Isoniazid in patient plasma may cause a false-positive result on the complement-dependent cytotoxicity test. Hum Immunol. 2009 Sep;70(9):758-9 Authors: Poli F, Innocente A, Cagni N, Brambilla C, Crespiatico L, Colombo MB, Scalamogna M Correct definition of clinically relevant anti-HLA antibodies is important for transplant organ allocation and outcome. We describe a candidate for kidney transplantation who was treated with isoniazid because of active tuberculosis. The patient's serum gave a positive antibody result on screening with the complement-dependent cytotoxicity (CDC) test but a negative result on screening with a bead-based assay (Luminex). The clinical history indicated no immunologic stimuli. Subsequent testing on fresh serum samples confirmed the discrepancy between CDC and Luminex results. An autologous cross-match test gave negative results, and the antibodies were sensitive to dithiothreitol treatment. We postulated that nonspecific binding of drug-antibody complexes to panel lymphocytes in the CDC test may have caused the observed lympholysis. This case, although isolated, emphasizes the importance of the combined use of CDC and solid phase assays. The CDC results alone would ha! ve led to the erroneous conclusion that the patient was highly sensitized. PMID: 19539003 [PubMed - indexed for MEDLINE] | | |
| Effects of mechanical stretch on collagen and cross-linking in engineered blood vessels.
February 2, 2010 at 4:47 PM
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| | Effects of mechanical stretch on collagen and cross-linking in engineered blood vessels. Cell Transplant. 2009;18(8):915-21 Authors: Solan A, Dahl SL, Niklason LE It has been shown that mechanical stimulation affects the physical properties of multiple types of engineered tissues. However, the optimum regimen for applying cyclic radial stretch to engineered arteries is not well understood. To this end, the effect of mechanical stretch on the development of engineered blood vessels was analyzed in constructs grown from porcine vascular smooth muscle cells. Cyclic radial distension was applied during vessel culture at three rates: 0 beats per minute (bpm), 90 bpm, and 165 bpm. At the end of the 7-week culture period, harvested vessels were analyzed with respect to physical characteristics. Importantly, mechanical stretch at 165 bpm resulted in a significant increase in rupture strength in engineered constructs over nonstretched controls. Stress-strain data and maximal elastic moduli from vessels grown at the three stretch rates indicate enhanced physical properties with increasing pulse rate. In order to investigate the role ! of collagen cross-linking in the improved mechanical characteristics, collagen cross-link density was quantified by HPLC. Vessels grown with mechanical stretch had somewhat more collagen and higher burst pressures than nonpulsed control vessels. Pulsation did not increase collagen cross-link density. Thus, increased wall thickness and somewhat elevated collagen concentrations, but not collagen cross-link density, appeared to be responsible for increased burst strength. PMID: 19500474 [PubMed - indexed for MEDLINE] | | |
| Transforming growth factor beta1 and laminin-111 cooperate in the induction of interleukin-16 expression in synovial fibroblasts from patients with rheumatoid arthritis.
February 2, 2010 at 4:47 PM
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| | Transforming growth factor beta1 and laminin-111 cooperate in the induction of interleukin-16 expression in synovial fibroblasts from patients with rheumatoid arthritis. Ann Rheum Dis. 2010 Jan;69(1):270-5 Authors: Warstat K, Hoberg M, Rudert M, Tsui S, Pap T, Angres B, Essl M, Smith TJ, Cruikshank WW, Klein G, Gay S, Aicher WK OBJECTIVES: In synovial tissues of patients with rheumatoid arthritis (RA), strong expression of laminins and integrins co-localises with increased expression of inflammatory cytokines. Synovial fibroblasts (SF) contribute to the pathogenesis of RA through increased expression of cytokines and chemoattractant factors, one of which is interleukin-16 (IL16). A study was undertaken to investigate the regulatory pathways of IL16 in SF from patients with RA (RA-SF) and osteoarthritis (OA-SF). METHODS: SF were seeded in laminin-coated flasks and activated by the addition of cytokines. The expression of IL16 was investigated by quantitative RT-PCR, immunoblotting and ELISA; its biological activity was determined by a cell migration assay. Cell-matrix interactions were investigated by cell binding and attachment assays. Relevant intracellular signalling pathways were studied by immunoblotting and with pharmacological blocking reagents. RESULTS: Stimulation of SF with tran! sforming growth factor beta(1)(TGF-beta(1)) and growth on laminin-111 (LM-111) significantly increased the expression of IL16. Binding to LM-111 induced significantly more IL16 mRNA in RA-SF than in OA-SF (p<0.05). The IL16 cytokine was detected in supernatants of TGF-beta(1)-activated and in LM-111+TGF-beta(1)-activated RA-SF (38 to 62 pg/ml), but not in supernatants of OA-SF. This IL16 regulation involved p38MAPK, ERK1/2 and SMAD2 signalling, but not NFkappaB. CONCLUSIONS: Binding of RA-SF to LM-111 in the presence of TGF-beta(1) triggers a significant IL16 response and thus may contribute to the infiltration of CD4+ lymphocytes into synovial tissues. This mode of IL16 induction represents a novel pathway leading to IL16 production in RA-SF but not in OA-SF, which operates independently of NFkappaB signalling. PMID: 19279017 [PubMed - indexed for MEDLINE] | | | |
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