| Advisory/Correction
September 8, 2009 at 4:57 pm
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| | Based on incorrect information on the CIRM Web site, the item below states that Stuart Orkin is currently chairman of the CIRM Grants Working Group. However, he told us in an email that he resigned last November and is no longer on the panel. We are querying CIRM concerning the current status of the chairman's position. |
| CIRM President to Gain More Clout in Competition for Millions in Grants
September 8, 2009 at 3:52 pm
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| | The California stem cell agency is moving to strengthen the hand of its president in the review of applications for hundreds of millions of dollars in grants.The proposal comes before the agency's Grants Working Group tomorrow morning at a two-day meeting in San Francisco to consider applications for its ambitious $210 million disease team program, the largest single research grant round in CIRM |
| Mayo Clinic researchers find lung cancer oncogene holds key to turning off cancer stem cells
September 8, 2009 at 2:26 pm
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| 4 Balzan 2009 prize winners announced in Milan
September 8, 2009 at 1:26 pm
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| Beike Biotech Adds International Executives to Strengthen Current Technologies and Develop Future Pipeline
September 8, 2009 at 10:25 am
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| Sangamo's Zinc Finger Nuclease Technology Used to Efficiently Modify Human Stem Cells
September 8, 2009 at 8:24 am
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| Induction of Alloantigen-Specific Human T Regulatory Cells by Vasoactive Intestinal Peptide.
September 8, 2009 at 7:43 am
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| | Induction of Alloantigen-Specific Human T Regulatory Cells by Vasoactive Intestinal Peptide. J Immunol. 2009 Sep 4; Authors: Pozo D, Anderson P, Gonzalez-Rey E T regulatory cells (Tregs) are instrumental in the maintenance of immunological tolerance. Although Treg-based immunotherapy proved successful in preclinical autoimmunity and transplantation, factors involved in the generation of human Ag-specific Tregs are poorly known. In this study, we show that treatment of human CD4(+)CD25(-) T cells with the cytokine-like vasoactive intestinal peptide (VIP) during in vitro stimulation induces an anergic FoxP3(+)CD4(+)CD25(high) T cell subset displaying potent regulatory activities against allospecific effector T cells, irrespective of the presence of naturally occurring Tregs. VIP-tolerant T cells are characterized by incapability to progress to S phase of cell cycle during stimulation with HLA-disparate APCs by negatively affecting the synthesis of cyclins D3 and E, the activation of cyclin-dependent kinases (cdk)2 and cdk4, and the down-regulation of the cdk inhibitor p27(kip1). VIP interaction with the type 1 VIP receptor and subsequent activation of cAMP/protein kinase A pathway play a major role in all these effects. Moreover, VIP-tolerant T cells protect against acute graft-vs-host disease in a mouse model of allogeneic bone marrow transplantation. The infusion of VIP-tolerant T cells together with the graft significantly reduces the clinical signs and mortality rate typical of the graft-vs-host disease. These effects are mediated by impairing allogeneic haplotype-specific responses of donor CD4(+) cells in the transplanted animals. Our results suggest that including alloantigen-specific VIP-generated Tregs may be a valuable tool in therapeutic interventions to promote immunotolerance toward allogeneic grafts and to reduce the need of general immunosuppressive drugs. PMID: 19734220 [PubMed - as supplied by publisher] |
| Polyurethane-based leukocyte-inspired biocidal materials.
September 8, 2009 at 7:43 am
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| | Polyurethane-based leukocyte-inspired biocidal materials. Biomaterials. 2009 Sep 3; Authors: Amitai G, Andersen J, Wargo S, Asche G, Chir J, Koepsel R, Russell AJ During the neutrophil respiratory burst myeloperoxidase uses hydrogen peroxide and chloride ion to generate hypochlorite which kills pathogens. Synthetic antimicrobial materials based on this chemistry are described herein. The oxidizing enzymes glucose oxidase (GOX) and horseradish peroxidase (HRP) catalyze two reactions in tandem using glucose, hydrogen peroxide and sodium halide (iodide or bromide). The final product of these two consecutive enzymatic reactions is either iodine or bromine. HRP, acting as haloperoxidase, utilizes the H(2)O(2) generated by GOX to oxidize halide ions into free halogens. Typically, 15 units/ml HRP and 25 units/ml GOX reacted with 0.8mm NaI and 5mm glucose to generate 5-7ppm free iodine within 30min. Medical grade polyurethane ChronoFlex AR (CF) was electrospun together with GOX and HRP. The electrospun fibers were collected as a uniform, water-insoluble, flexible elastomeric matrix with an average fiber diameter of 1+/-0.2mum. Biocidal activity of CF/enzyme fibers resulted in >6-log unit reduction of both Escherichia coli and Staphylococcus aureus challenges. A time-course of biocidal activity displayed a 3-4log reduction of E. coli and S. aureus within the first 5min and complete kill (>6logs) within 15min. A dose-response study of fiber weight (0.5-30mg/ml) exhibited complete kill of E. coli (>6logs) and at least 99.99% S. aureus kill (>4logs) with as little as 1mg fiber. The fibers were reusable with slightly less activity on the second use and significant activity after continuous soaking in buffer for up to 7 days. Electrospun CF/GOX/HRP fibers adhered to a thin film with embedded NaI and glucose caused a complete kill of E. coli (>7-log units) and MRSA (6-log unit reduction) within 1h at 37 degrees C. PMID: 19733392 [PubMed - as supplied by publisher] |
| Transient Receptor Potential A1 and Cannabinoid Receptor Activity in Human Normal and Hyperplastic Prostate: Relation to Nerves and Interstitial Cells.
September 8, 2009 at 7:43 am
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| | Transient Receptor Potential A1 and Cannabinoid Receptor Activity in Human Normal and Hyperplastic Prostate: Relation to Nerves and Interstitial Cells. Eur Urol. 2009 Aug 28; Authors: Gratzke C, Weinhold P, Reich O, Seitz M, Schlenker B, Stief CG, Andersson KE, Hedlund P BACKGROUND: Ion channel transient receptor potential A1 (TRPA1) and cannabinoid (CB) receptors are involved in mechanoafferent signaling from the bladder and the urethra. OBJECTIVE: To characterize TRPA1-, CB1-, and CB2-receptor activities in the human prostate. DESIGN, SETTING, AND PARTICIPANTS: Prostate specimens were obtained from 12 patients undergoing radical prostatectomy. We studied expressions (n=6) of TRPA1, CB1, and CB2 receptors and effects of the TRPA1 agonists allyl isothiocyanate (AI), cinnamaldehyde (CA), sodium hydrogen sulfide (NaHS), and CP 55940 (a CB1/CB2 agonist) on prostatic preparations. MEASUREMENTS: Western blot, immunohistochemistry, and functional experiments were performed. RESULTS AND LIMITATIONS: Western blot detected expected bands for CB1, CB2, and TRPA1. TRPA1 immunoreactivity was located on nerves that were positive for CB1, CB2, calcitonin gene-related peptide (CGRP), nitric oxide synthase (NOS), or vesicular acetylcholine transporter (VAChT). CB1 and CB2 immunoreactivity was found on nerves that were positive for NOS, VAChT, or CGRP. Adrenergic nerves were not immunoreactive for TRPA1, CB1, or CB2. In nodular hyperplasia, nerves containing the above markers were scarce or absent. TRPA1 immunoreactivity was detected in cyclic guanosine monophosphate-positive basal cells of the glandular epithelium. Basal or subepithelial TRPA1-immunoreactive cells contained vimentin and c-kit immunoreactivity. CA and NaHS relaxed precontracted preparations by 55+/-7% and 35+/-3% (n=6 for each). CP 55940, NaHS, AI, capsaicin, and CA decreased nerve contractions up to 27%, 80%, 47%, and 87%, respectively (n=6 for each). CONCLUSIONS: The distribution and function of TRPA1 and CB receptors in prostatic tissue suggest a role for these receptors in mechanoafferent signals, epithelial homeostasis, emission, or inflammation of the human prostate. PMID: 19733001 [PubMed - as supplied by publisher] |
| Streptavidin-Coated Magnetic Beads for DNA Strand Separation Implicate a Multitude of Problems During Cell-SELEX.
September 8, 2009 at 7:43 am
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| | Streptavidin-Coated Magnetic Beads for DNA Strand Separation Implicate a Multitude of Problems During Cell-SELEX. Oligonucleotides. 2009 Sep 4; Authors: Paul A, Avci-Adali M, Ziemer G, Wendel HP Using whole living cells as a target for SELEX (systematic evolution of ligands by exponential enrichment) experiments represents a promising method to generate cell receptor-specific aptamers. These aptamers have a huge potential in diagnostics, therapeutics, imaging, regenerative medicine, and target validation. During the SELEX for selecting DNA aptamers, one important step is the separation of 2 DNA strands to yield one of the 2 strands as single-stranded DNA aptamer. This is being done routinely by biotin labeling of the complementary DNA strand to the desired aptamer and then separating the DNA strand by using streptavidin-coated magnetic beads. After immobilization of the double-stranded DNA on these magnetic beads and alkaline denaturation, the non-biotinylated strand is being eluted and the biotinylated strand is retarded. Using Western blot analysis, we demonstrated the detachment of covalent-bonded streptavidin from the bead surface after alkaline treatment. The eluates were also contaminated with undesired biotinylated strands. Furthermore, a streptavidin-induced aggregation of target cells was demonstrated by flow cytometry and microscopic methods. Cell-specific enrichment of aptamers was not possible due to clustering and patching effects triggered by streptavidin. Therefore, the use of streptavidin-coated magnetic beads for DNA strand separation should be examined thoroughly, especially for cell-SELEX applications. PMID: 19732022 [PubMed - as supplied by publisher] |
| Effect of a Novel Recombinant Protein of FibronectinIII7-10/Cadherin 11 EC1-2 on Osteoblastic Adhesion and Differentiation.
September 8, 2009 at 7:07 am
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| | Effect of a Novel Recombinant Protein of FibronectinIII7-10/Cadherin 11 EC1-2 on Osteoblastic Adhesion and Differentiation. Biosci Biotechnol Biochem. 2009 Sep 7; Authors: Zhang Y, Zhou Y, Zhu J, Dong S, Li C, Xiang Q The limitations of specific adhesion and osteoblastic differentiation are current problems in bone tissue engineering. The aim of this study was to investigate the effect of a novel recombinant protein of fibronectin module III7-10/cadherin 11 EC1-2 (rFN/CDH) on cell adhesion and differentiation. Gene coding rFN/CDH was engineered by a homology modeling strategy, and an expression plasmid was constructed by standard DNA techniques. The rFN/CDH protein was expressed in Rosetta-gami (DE3), an improved Escherichia coli system. MC3T3-E1 cell centrifugal adhesive assay indicated that the adhesive capacity of rFN/CDH was significantly improved. Quantitative analysis of two osteogenic markers, osteocalcin mRNA expression and alkaline phosphatase activity, indicated that they were further up-regulated when human mesenchymal stem cells were cultured for 7-10 d on rFN/CDH pre-coated surfaces. These results suggest that rFN/CDH possesses an enhanced dual biofunctionality in osteoblastic adhesion and differentiation, and a promising application can be expected in biomimetic strategies and biomaterial development. PMID: 19734674 [PubMed - as supplied by publisher] |
| Mesenchymal Stem Cells for Craniofacial Tissue Regeneration: Designing Hydrogel Delivery Vehicles.
September 8, 2009 at 7:07 am
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| | Mesenchymal Stem Cells for Craniofacial Tissue Regeneration: Designing Hydrogel Delivery Vehicles. J Dent Res. 2009 Aug;88(8):681-692 Authors: Salinas CN, Anseth KS Craniofacial injuries require a variety of different cell types to repopulate areas of bone, cartilage, tendon, and fat. Mesenchymal stem cells (MSCs) provide a multipotent cell source for tissue engineering of this area, particularly when the cells are delivered via a 3D hydrogel environment. MSC differentiation into cartilage, bone, and fat has been investigated through a variety of techniques, some of which include the use of synthetic hydrogel scaffolds, integration of extracellular matrix components and other natural gel chemistries, microparticle delivery of growth factors, simultaneous mechanical stimulation, and the delivery of microRNA. This review aims to summarize the most recent studies involving the synthesis and application of 3D hydrogels to induce the differentiation of encapsulated MSCs and their subsequent matrix production. PMID: 19734453 [PubMed - as supplied by publisher] |
| Microporous Collagen Spheres Produced Via Thermally Induced Phase Separation for Tissue Regeneration.
September 8, 2009 at 7:07 am
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| | Microporous Collagen Spheres Produced Via Thermally Induced Phase Separation for Tissue Regeneration. Acta Biomater. 2009 Sep 3; Authors: Keshaw H, Thapar N, Burns AJ, Mordan N, Knowles JC, Forbes A, Day RM Collagen is an abundant protein found in the extracellular matrix of many tissues. Due to its biocompatibility, it is a potentially ideal biomaterial for many tissue engineering applications. However, harvested collagen often requires restructuring into a three-dimensional matrix to facilitate applications such as implantation into poorly accessible tissue cavities. The aim of the current study was to produce a conformable collagen-based scaffold material capable of supporting tissue regeneration for use in wound repair applications. Microporous collagen spheres were prepared using a thermally induced phase separation (TIPS) technique and their biocompatibility assessed. The collagen spheres were successfully cross-linked with glutaraldehyde vapour rendering them mechanically more stable. When cultured with myofibroblasts the collagen spheres stimulated a prolonged significant increase in secretion of the angiogenic growth factor, vascular endothelial growth factor (VEGF), compared with cells alone. Control polycaprolactone (PCL) spheres failed to stimulate a similar prolonged increase in VEGF secretion. An enhanced angiogenic effect was also seen in vivo using the chick embryo chorioallantoic membrane assay, where a significant increase in the number of blood vessels converging towards collagen spheres was observed compared with control PCL spheres. The results from this study indicate that microporous collagen spheres produced using TIPS are biologically active and could offer a novel conformable scaffold for tissue regeneration in poorly accessible wounds. PMID: 19733702 [PubMed - as supplied by publisher] |
| In Vitro Engineered Cartilage Using Synovium-Derived Mesenchymal Stem Cells with Injectable Gellan Hydrogels.
September 8, 2009 at 7:07 am
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| | In Vitro Engineered Cartilage Using Synovium-Derived Mesenchymal Stem Cells with Injectable Gellan Hydrogels. Acta Biomater. 2009 Sep 3; Authors: Fan J, Gong Y, Ren L, R Varshney R, Cai D, Wang DA Synovium-derived mesenchymal stem cells (SMSCs), a novel line of stem cells, are regarded as a promising cell source for cartilage tissue engineering. The goal of this study was to investigate rabbit SMSCs coupled with injectable gellan hydrogels for in vitro engineered cartilage. SMSCs were isolated from rabbit synovial tissue, amplified to passage 4 in monolayer, and encapsulated in injectable gellan hydrogels, constructs of which were cultured in chondrogenic medium supplemented with TGF-beta1, TGF-beta3 or BMP-2 for up to 42 days. Quality of constructs was assessed in terms of cell proliferation and chondrocytic gene/protein expression using WST-1 assay, real-time RT-PCR, biochemical analysis, histology and immunhistochemical analysis. Results indicate that the viability of SMSCs in the hydrogels treated with TGF-beta1, TGF-beta3 and BMP-2 respectively remained high at culture time. The constructs formed cartilaginous tissue with the expression of chondrocytic genes (collagen type II, aggrecan, biglycan, SOX 9) and cartilaginous matrix (sulphated glycosaminoglycan [sGAG] and collagen) as early as 21 days in culture. Both TGF-beta1 and TGF-beta3 treated SMSC-laden hydrogels showed more chondrogenesis as compared to BMP-2 treated SMSC-laden hydrogels. It demonstrates that injectable SMSC-laden gels, when treated with TGF-beta1, TGF-beta3 or BMP-2, are highly competent for in vitro engineered cartilage formation, which lays a foundation for their potential application in clinical cartilage repair. PMID: 19733701 [PubMed - as supplied by publisher] |
| In vitro model of mesenchymal condensation during chondrogenic development.
September 8, 2009 at 7:07 am
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| | In vitro model of mesenchymal condensation during chondrogenic development. Biomaterials. 2009 Sep 2; Authors: Ghosh S, Laha M, Mondal S, Sengupta S, Kaplan DL Mesenchymal condensation is a pre-requisite of chondrogenesis during embryonic development. The current understanding of chondrogenesis is limited in terms of chondrogenic condensation mechanisms. In particular, the role of matrix stiffness on homotypic cell-cell interactions leading to the establishment of distinct aggregated chondrogenic morphology from mesenchymal cells is unclear. An in vitro biomaterials-based model to assess the interactions of matrix stiffness on chondrogensis is described herein, where by sensing subtle variation in morphology and stiffness of nanofibrous silk protein matrixes human mesenchymal stem cells migrated and assumed aggregated morphologies, mimicking early stage chondrogenesis. This simple in vitro model system has potential to play a significant role to gain insight into underlying mechanisms of mesenchymal condensation steps during chondrogenesis, integrating concepts of developmental biology, biomaterials and tissue engineering. PMID: 19732950 [PubMed - as supplied by publisher] |
| Meniscal Repair.
September 8, 2009 at 7:07 am
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| | Meniscal Repair. Arthroscopy. 2009 Sep;25(9):1033-1044 Authors: Stärke C, Kopf S, Petersen W, Becker R The meniscus plays an important role in preventing osteoarthritis of the knee. Repair of a meniscal lesion should be strongly considered if the tear is peripheral and longitudinal, with concurrent anterior cruciate ligament reconstruction, and in younger patients. The probability of healing is decreased in complex or degenerative tears, central tears, and tears in unstable knees. Age or extension of the tear into the avascular area are not exclusion criteria. Numerous repair techniques are available, and suture repair seems to provide superior biomechanical stability. However, the clinical success rate does not correlate well with the mechanical strength of the repair technique. Biologic factors might be of greater importance to the success of meniscal repair than the surgical technique. Therefore, the decision on the most appropriate repair technique should not rely on biomechanical parameters alone. Contemporary all-inside repair systems have decreased the operating time and the level of surgical skill required. Despite the ease of use, there is a potential for complications because of the close proximity of vessels, nerves, and tendons, of which the surgeon should be aware. There is no clear consensus on postoperative rehabilitation. Weight bearing in extension would most likely not be crucial in typical longitudinal lesions. However, higher degrees of flexion, particularly with weight bearing, give rise to large excursions of the menisci and to shear motions, and should therefore be advised carefully. Long-term studies show a decline in success rates with time. Further studies are needed to clarify the factors relevant to the healing of the menisci. Tissue engineering techniques to enhance the healing in situ are promising but have not yet evolved to a practicable level. PMID: 19732643 [PubMed - as supplied by publisher] |
| An alginate hydrogel matrix for the localised delivery of a fibroblast/keratinocyte co-culture.
September 8, 2009 at 7:07 am
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| | An alginate hydrogel matrix for the localised delivery of a fibroblast/keratinocyte co-culture. Biotechnol J. 2009 May;4(5):730-7 Authors: Hunt NC, Shelton RM, Grover L There is significant interest in the development of tissue-engineered skin analogues, which replace both the dermal and the epidermal layer, without the use of animal or human derived products such as collagen or de-epidermalised dermis. In this study, we proposed that alginate hydrogel could be used to encapsulate fibroblasts and that keratinocytes could be cultured on the surface to form a bilayered structure, which could be used to deliver the co-culture to a wound bed, initially providing wound closure and eventually expediting the healing process. Encapsulation of fibroblasts in 2 and 5% w/v alginate hydrogel effectively inhibited their proliferation, whilst maintaining cell viability allowing keratinocytes to grow uninhibited by fibroblast overgrowth to produce a stratified epidermal layer. It was shown that the alginate degradation process was not influenced by the presence of fibroblasts within the hydrogel and that lowering the alginate concentration from 5 to 2% w/v increased the rate of degradation. Fibroblasts released from the scaffold were able to secrete extracellular matrix (ECM) and thus should replace the degrading scaffold with normal ECM following application to the wound site. These findings demonstrate that alginate hydrogel may be an effective delivery vehicle and scaffold for the healing of full-thickness skin wounds. PMID: 19452469 [PubMed - indexed for MEDLINE] |
| Simultaneous detection of ERK-, p38-, and JNK-MAPK phosphorylation in human adipose-derived stem cells using the cytometric bead array technology.
September 8, 2009 at 6:47 am
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| | Simultaneous detection of ERK-, p38-, and JNK-MAPK phosphorylation in human adipose-derived stem cells using the cytometric bead array technology. J Immunol Methods. 2009 Sep 2; Authors: Schubert R, Geiger H, Zielen S, Baer PC Despite expanded research in stem cell biology, little is known about the mechanisms underlying migration, growth, and differentiation of adipose-derived adult mesenchymal stem cells (ASC). The simultaneous measurement of intracellular pathways opens new avenues to gain further insights in these processes. We used the Cytometric Bead Array (CBA) Flex Set technology to simultaneously analyze protein phosphorylation after stimulation of ASC and compared the results with data generated by corresponding Western blots. Signal transduction of ASC was stimulated by epidermal growth factor (EGF) and analyzed by determining phosphorylation of mitogen-activated protein kinases (MAPKs) ERK, p38, and JNK by Western blotting and CBA. After incubation with EGF, all MAPKs were significantly but differentially phosphorylated depending on time and dose. Furthermore, the ERK-response was abolished by EGF-R antagonist AG 1478 and kinase inhibitor PD98059, whereas p38 and JNK were only inhibited by AG1478. The stimulation and inhibition profiles between the two assays were highly comparable and the data were significantly correlated. In the present study we demonstrated that the CBA technology offers a reliable and convenient method for multiplexing of phospho-proteins in the evaluation of signal transduction pathways of adipose-derived mesenchymal stem cells. PMID: 19733175 [PubMed - as supplied by publisher] | | | 
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