| Shestack's Words Stir Ire in York
August 27, 2009 at 6:33 pm
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| | One of the directors of the California stem cell agency has become embroiled in a flap about billboards in a small Pennsylvania town better known for making Harleys and animal crackers than for scientific research.The director is Jonathan Shestack, a nationally known autism patient advocate and Hollywood film producer (Air Force One). The town is York, home to a motorcycle factory and the |
| Geron's Setback with Testing Its hESC Therapy in Humans Is Chalked Up to FDA's Continued Cautionary Stance
August 27, 2009 at 5:21 pm
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| The path to new antibiotics
August 27, 2009 at 2:19 pm
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| Nanoparticles as tools to study and control stem cells.
August 27, 2009 at 11:45 am
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| | Nanoparticles as tools to study and control stem cells. J Cell Biochem. 2009 Aug 25; Authors: Ferreira L The use of nanoparticles in stem cell research is relatively recent, although very significant in the last 5 years with the publication of about 400 papers. The recent advances in the preparation of some nanomaterials, growing awareness of material science and tissue engineering researchers regarding the potential of stem cells for regenerative medicine, and advances in stem cell biology have contributed towards the boost of this research field in the last few years. Most of the research has been focused in the development of new nanoparticles for stem cell imaging; however, these nanoparticles have several potential applications such as intracellular drug carriers to control stem cell differentiation and biosensors to monitor in real time the intracellular levels of relevant biomolecules/enzymes. This review examines recent advances in the use of nanoparticles for stem cell tracking, differentiation and biosensing. We further discuss their utility and the potential concerns regarding their cytotoxicity. J. Cell. Biochem. (c) 2009 Wiley-Liss, Inc. PMID: 19708027 [PubMed - as supplied by publisher] |
| Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/beta-catenin pathway.
August 27, 2009 at 11:45 am
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| | Aspirin induces apoptosis in mesenchymal stem cells requiring Wnt/beta-catenin pathway. Cell Prolif. 2009 Aug 25; Authors: Deng L, Hu S, Baydoun AR, Chen J, Chen X, Cong X Abstract Background and Objectives: Mesenchymal stem cells (MSC) are multipotent progenitor cells that are have found use in regenerative medicine. We have previously observed that aspirin, a widely used anti-inflammatory drug, inhibits MSC proliferation. Here we have aimed to elucidate whether aspirin induces MSC apoptosis and whether this is modulated through the Wnt/beta-catenin pathway. Materials and methods: Apoptosis of MSCs was assessed using Hoechst 33342 dye and an Annexin V-FITC/PI Apoptosis Kit. Expression of protein and protein phosphorylation were investigated using Western blot analysis. Caspase-3 activity was detected by applying a caspase-3/CPP32 Colorimetric Assay Kit. Results: In these MSCs, aspirin induced morphological changes characteristic of apoptosis, cytochrome c release from mitochondria, and caspase-3 activation. Stimulating the Wnt/beta-catenin pathway by both Wnt 3a and GSK-3beta inhibitors (LiCl and SB 216763), blocked aspirin-induced apoptosis and protected mitochondrial function, as demonstrated by decreased cytochrome c release and caspase-3 activity. Aspirin initially caused a time-dependent decrease in COX-2 expression but subsequently, and unexpectedly, elevated the latter. Stimulation of COX-2 expression by aspirin was further enhanced following stimulation of the Wnt/beta-catenin pathway. Application of the COX-2 inhibitor NS-398 suppressed elevated COX-2 expression and promoted aspirin-induced apoptosis. Conclusion: These results demonstrate that the Wnt/beta-catenin pathway is a key modulator of aspirin-induced apoptosis in MSCs by regulation of mitochrondrial/caspase-3 function. More importantly, our findings suggest that aspirin may influence MSC survival under certain conditions; therefore, it should be used with caution when considering regenerative MSC transplantation in patients with concomitant chronic inflammatory diseases such as arthritis. PMID: 19706045 [PubMed - as supplied by publisher] |
| Generation of Stable Co-cultures of Vascular Cells in a Honeycomb Alginate Scaffold.
August 27, 2009 at 11:45 am
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| | Generation of Stable Co-cultures of Vascular Cells in a Honeycomb Alginate Scaffold. Tissue Eng Part A. 2009 Aug 25; Authors: Rabbany SY, Yamamoto M, James D, Li H, Butler J, Rafii S Scaffold-guided vascular tissue engineering has been investigated as a means to generate functional and transplantable vascular tissue grafts that increase the efficacy of cell-based therapeutic strategies in regenerative medicine. In this study, we employed confocal microscopy and 3-dimensional reconstruction to assess the engraftment and growth potential of vascular cells within an alginate scaffold with aligned pores. We fabricated honeycomb alginate scaffolds with aligned pores of which surface was immobilized with fibronectin and subsequently coated with matrigel. Endothelial cells (ECs) were seeded into aligned pore scaffolds in the presence and absence of human smooth muscle cells. We show that ECs seeded into alginate scaffolds attach on the surface of aligned pores in vitro, giving rise to stable co-cultures of vascular cells. Moreover, the 3-D alginate depots containing the cells were exposed to laminar flow in order to recapitulate physiological shear stress found in the vasculature in vivo. After the flow exposure, the scaffold remains intact and some cells remaining adhered to the scaffold are aligned in the flow direction. These studies demonstrate that alginate scaffolds provide a suitable matrix for establishing durable angiogenic modules that may ultimately enhance organ revascularization. PMID: 19705957 [PubMed - as supplied by publisher] |
| Biomineralization of calcium phosphate on human hair protein film and formation of a novel hydroxyapatite-protein composite material.
August 27, 2009 at 10:32 am
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| | Biomineralization of calcium phosphate on human hair protein film and formation of a novel hydroxyapatite-protein composite material. J Biomed Mater Res B Appl Biomater. 2009 Aug 25; Authors: Fujii T, Tanaka T, Ohkawa K Human hair protein can be used not only as a totally biodegradable material but also as a "self-originated" material, which may avoid an undesirable immune reaction, if it has been prepared from a certain individual and implanted into the same person. In this study, a novel organic-inorganic composite, which contains human hair proteins and hydroxyapatite, was investigated as biomineral-scaffolding materials. The human hair protein was extracted by our original "Shindai method" (Nakamura et al., Biol Pharm Bull 2002;25:569-572; Fujii et al., Biol Pharm Bull 2004;27:89-93). The extracts were exposed to CaCl(2) solution for fabrication into flat films, which mainly consisted of alpha-keratin. After washing with distilled water, approximately 3 Ca(2+) ions per 1 keratin molecule bound to the film. The Ca(2+)-binding was slightly sensitive to the ionic strengths, and only Mg(2+) inhibited binding of Ca(2+). A composite of the human hair protein and calcium phosphate was prepared via alternate soaking processes using CaCl(2) and Na(2)HPO(4) solutions. As the soaking cycle proceeded, the film weight increased and its color became white, indicating successful deposition of calcium phosphate. The diameters of deposited calcium phosphate particles were about 2-4 mum. The proteins were not solubilized and degraded during the soaking processes. FTIR and WAXD analyses indicated that calcium phosphate was first deposited as amorphous, then transformed into crystalline monohydrogen calcium phosphate during the earlier soaking cycle, and, via octacalcium phosphate, finally converted into hydroxyapatite after 20 cycles. The present human hair protein/hydroxyapatite composite film is a "self-originated" and also an intact proteinaceous material without chemical modification, and thus, a promising material for hard tissue engineering. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009. PMID: 19708078 [PubMed - as supplied by publisher] |
| Human mesenchymal stem cells: Influence of oxygen pressure on proliferation and chondrogenic differentiation in fibrin glue in vitro.
August 27, 2009 at 10:32 am
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| | Human mesenchymal stem cells: Influence of oxygen pressure on proliferation and chondrogenic differentiation in fibrin glue in vitro. J Biomed Mater Res A. 2009 Aug 25; Authors: Baumgartner L, Arnhold S, Brixius K, Addicks K, Bloch W Tissue engineering using biomaterials is a promising solution for cartilage replacement. The purpose of this study was to investigate whether the fibrin sealant Tissucol(R) provides a suitable scaffold for re-implanting stem cells during chondrogenic replacement therapy. Pluripotent stem cells were isolated from adult human bone marrow (hMSCs), cultured and characterized by FACS (CD105+/CD106+, CD45-/CD14-/CD34-). A large-holed porous hMSC-containing fibrin matrix was built that allowed hMSCs to survive throughout the period of culture (42 days) in either proliferation or chondrogenic differentiation medium under normoxic (21% O2) or hypoxic (3% O2) conditions. Morphology (as determined by electron microscopy) and proliferation (Ki67 staining) of the embedded hMSCs did not markedly vary under normoxic and hypoxic culture even after 42 days in culture. The stem cell marker Oct-4 was expressed during the whole culture period. Under chondrogenic differentiation conditions, especially under hypoxic conditions, we observed rounded chondrocyte-like cell types and a chondral phenotype assessed by mRNA expression of collagen II and Alcian blue staining. hMSCs seeded into large-holed porous preparations of Tissucol(R) survive, proliferate and keep their stem cell character. Furthermore, culturing the cells in a corresponding medium induces chondrogenic differentiation, which could be remarkably and significantly enhanced under hypoxic conditions. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009. PMID: 19708077 [PubMed - as supplied by publisher] |
| A novel porous bioceramics scaffold by accumulating hydroxyapatite spherules for large bone tissue engineering in vivo. I. Preparation and characterization of scaffold.
August 27, 2009 at 10:32 am
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| | A novel porous bioceramics scaffold by accumulating hydroxyapatite spherules for large bone tissue engineering in vivo. I. Preparation and characterization of scaffold. J Biomed Mater Res A. 2009 Aug 25; Authors: Peng Q, Jiang F, Huang P, Zhou S, Weng J, Bao C, Zhang C, Yu H A novel scaffold with large dimension of 3-4 cm in length and 1-1.5 cm in diameter was designed and fabricated for engineering large bone tissue in vivo. The scaffold was constructed by filling hydroxyapatite (HA) spherules into a porous HA tube. The HA spherules were prepared by chitin sol emulsification in oil and gelation in situ, and their sizes can be controlled by parameters such as stirring rate and oil temperature. Accumulation of the HA spherules formed the interconnected pores in the scaffold, and the porosity and microstructure of the scaffold can be controlled by varying the size and miroporous structure of the HA spherules. Porous HA tube coated with a thin layer of poly(L-lactic acid) (PLA) held the HA spherules together and provided the initial strength of scaffolds. HA spherules can be easily compounded with biological substance, such as comminuted bone granules, before being filled into the HA tubes. A pilot study is underway to use the hybrid scaffolds at different sites such as muscle, peritoneum, and bone side. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009. PMID: 19708076 [PubMed - as supplied by publisher] |
| Characterization of the in vitro macrophage response and in vivo host response to poly(ethylene glycol)-based hydrogels.
August 27, 2009 at 10:32 am
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| | Characterization of the in vitro macrophage response and in vivo host response to poly(ethylene glycol)-based hydrogels. J Biomed Mater Res A. 2009 Aug 25; Authors: Lynn AD, Kyriakides TR, Bryant SJ Photopolymerizable poly(ethylene glycol) (PEG)- based hydrogels have great potential as in vivo cell delivery vehicles for tissue engineering. However, their success in vivo will be dependent on the host response. The objectives for this study were to explore the in vivo host response and in vitro macrophage response to commonly used PEG-based hydrogels, PEG and PEG containing RGD. Acellular hydrogels were implanted subcutaneously into c57bl/6 mice and the foreign body response (FBR) was compared to medical grade silicone. Our findings demonstrated PEG-RGD hydrogels resulted in a FBR similar to silicone, while PEG-only hydrogels resulted in a robust inflammatory reaction characterized by a thick layer of macrophages at the material surface with evidence of gel degradation. In vitro, bone marrow-derived primary macrophages adhered well and similarly to PEG-based hydrogels, silicone, and tissue culture polystyrene when cultured for 4 days. Significantly higher gene expressions of the proinflammatory cytokines, TNF-alpha and Il-1beta, were found in macrophages seeded onto PEG compared to PEG-RGD and silicone at 1 and 2 days. PEG hydrogels were also shown to be susceptible to oxidative biodegradation. Our findings indicate that PEG-only hydrogels are proinflammatory while RGD attenuates this negative reaction leading to a moderate FBR. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009. PMID: 19708075 [PubMed - as supplied by publisher] |
| Nanoparticles as tools to study and control stem cells.
August 27, 2009 at 10:32 am
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| | Nanoparticles as tools to study and control stem cells. J Cell Biochem. 2009 Aug 25; Authors: Ferreira L The use of nanoparticles in stem cell research is relatively recent, although very significant in the last 5 years with the publication of about 400 papers. The recent advances in the preparation of some nanomaterials, growing awareness of material science and tissue engineering researchers regarding the potential of stem cells for regenerative medicine, and advances in stem cell biology have contributed towards the boost of this research field in the last few years. Most of the research has been focused in the development of new nanoparticles for stem cell imaging; however, these nanoparticles have several potential applications such as intracellular drug carriers to control stem cell differentiation and biosensors to monitor in real time the intracellular levels of relevant biomolecules/enzymes. This review examines recent advances in the use of nanoparticles for stem cell tracking, differentiation and biosensing. We further discuss their utility and the potential concerns regarding their cytotoxicity. J. Cell. Biochem. (c) 2009 Wiley-Liss, Inc. PMID: 19708027 [PubMed - as supplied by publisher] |
| Biological drugs targeting the immune response in the therapy of psoriasis.
August 27, 2009 at 10:32 am
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| | Biological drugs targeting the immune response in the therapy of psoriasis. Biologics. 2008 Dec;2(4):687-97 Authors: Pastore S, Gubinelli E, Leoni L, Raskovic D, Korkina L Chronic plaque psoriasis affects more than 2% of world population, has a chronic recurrent behavior, gives a heavy burden to the patients' quality of life, and hence remains a huge medical and social problem. The clinical results of conventional therapies of psoriasis are not satisfactory. According to the current knowledge of the molecular and cellular basis of psoriasis, it is defined as an immune-mediated chronic inflammatory and hyperproliferative skin disease. A new generation of biological drugs, targeting molecules and cells involved into perturbed pro-inflammatory immune response in the psoriatic skin and joints, has been recently designed and applied clinically. These biological agents are bioengineered proteins such as chimeric and humanized antibodies and fusion proteins. In particular, they comprise the antitumor necrosis factor-alpha agents etanercept, infliximab, and adalimumab, with clinical efficacy in both moderate-severe psoriasis and psoriatic arthritis, and the anti-CD11a efalizumab with selective therapeutic action exclusively in the skin. Here, we overview recent findings on the molecular pathways relevant to the inflammatory response in psoriasis and present our clinical experience with the drugs currently employed in the dermatologic manifestations, namely etanercept, infliximab, and efalizumab. The growing body of clinical data on the efficacy and safety of antipsoriasis biological drugs is reviewed as well. Particular focus is given to long-term safety concerns and feasibility of combined therapeutic protocols to ameliorate clinical results. PMID: 19707449 [PubMed - in process] |
| Biomimetic Modification of Porous TiNbZr Alloy Scaffold for Bone Tissue Engineering.
August 27, 2009 at 10:32 am
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| | Biomimetic Modification of Porous TiNbZr Alloy Scaffold for Bone Tissue Engineering. Tissue Eng Part A. 2009 Aug 25; Authors: Wang X, Li Y, Hodgson PD, Wen C Porous titanium and titanium alloys are of significant importance as scaffold materials for bone tissue engineering. In the present study, a new type of porous Ti alloy scaffold with biocompatible alloying elements, i.e. niobium (Nb) and zirconium (Zr) was prepared by a space-holder sintering method. This porous TiNbZr scaffold with a porosity of 69% exhibits a mechanical strength of 67 MPa and an elastic modulus of 3.9 GPa, resembling the mechanical properties of cortical bone. To improve the osteoconductivity, a Calcium Phosphate (Ca/P) coating was applied to the surface of the scaffold using a biomimetic method. The biocompatibility of the porous TiNbZr alloy scaffold before and after the biomimetic modification was assessed using the SaOS2 osteoblast-like cells. Cell culture results indicated that the porous TiNbZr scaffold is more favourable for cell adhesion and proliferation than its solid counterpart. By applying a Ca/P coating, the cell proliferation rate on the Ca/P coated scaffold was significantly improved. The results suggest that high strength porous TiNbZr scaffolds with an appropriate osteoconductive coating could be potentially used for bone tissue engineering application. PMID: 19705960 [PubMed - as supplied by publisher] |
| Generation of Stable Co-cultures of Vascular Cells in a Honeycomb Alginate Scaffold.
August 27, 2009 at 10:32 am
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| | Generation of Stable Co-cultures of Vascular Cells in a Honeycomb Alginate Scaffold. Tissue Eng Part A. 2009 Aug 25; Authors: Rabbany SY, Yamamoto M, James D, Li H, Butler J, Rafii S Scaffold-guided vascular tissue engineering has been investigated as a means to generate functional and transplantable vascular tissue grafts that increase the efficacy of cell-based therapeutic strategies in regenerative medicine. In this study, we employed confocal microscopy and 3-dimensional reconstruction to assess the engraftment and growth potential of vascular cells within an alginate scaffold with aligned pores. We fabricated honeycomb alginate scaffolds with aligned pores of which surface was immobilized with fibronectin and subsequently coated with matrigel. Endothelial cells (ECs) were seeded into aligned pore scaffolds in the presence and absence of human smooth muscle cells. We show that ECs seeded into alginate scaffolds attach on the surface of aligned pores in vitro, giving rise to stable co-cultures of vascular cells. Moreover, the 3-D alginate depots containing the cells were exposed to laminar flow in order to recapitulate physiological shear stress found in the vasculature in vivo. After the flow exposure, the scaffold remains intact and some cells remaining adhered to the scaffold are aligned in the flow direction. These studies demonstrate that alginate scaffolds provide a suitable matrix for establishing durable angiogenic modules that may ultimately enhance organ revascularization. PMID: 19705957 [PubMed - as supplied by publisher] |
| Self-Assembled Fmoc-Peptides as a Platform for the Formation of Nanostructures and Hydrogels.
August 27, 2009 at 10:32 am
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| | Self-Assembled Fmoc-Peptides as a Platform for the Formation of Nanostructures and Hydrogels. Biomacromolecules. 2009 Aug 25; Authors: Orbach R, Adler-Abramovich L, Zigerson S, Mironi-Harpaz I, Seliktar D, Gazit E Hydrogels are of great interest as a class of materials for tissue engineering, axonal regeneration, and controlled drug delivery, as they offer 3D interwoven scaffolds to support the growth of cells. Herein, we extend the family of the aromatic Fmoc-dipeptides with a library of new Fmoc-peptides, which include natural and synthetic amino acids with an aromatic nature. We describe the self-assembly of these Fmoc-peptides into various structures and characterize their distinctive molecular and physical properties. Moreover, we describe the fabrication of the bioactive RGD sequence into a hydrogel. This unique material offers new opportunities for developing cell-adhesive biomedical hydrogel scaffolds, as well as for establishing strategies to modify surfaces with bioactive materials. PMID: 19705843 [PubMed - as supplied by publisher] |
| [Research of repairing rabbit knee joint cartilage defect by compound material of fibrin glue and decalcified bone matrix (DBM) and chondrocytes]
August 27, 2009 at 10:32 am
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| | [Research of repairing rabbit knee joint cartilage defect by compound material of fibrin glue and decalcified bone matrix (DBM) and chondrocytes] Zhongguo Gu Shang. 2009 Jul;22(7):523-6 Authors: He J, Yang X, Yue PJ, Wang GY, Guo T, Zhao JN OBJECTIVE: To investigate the feasibility and effectivity of using compound material of fibrin glue and DBM as scaffolds for cartilage tissue engineering. METHODS: Chondrocytes isolated from articular cartilage were seeded into prepared scaffolds, after incubation for 4 weeks in vitro. Chondrocytes and fibrin glue and DBM constructs were implanted in the joint cave of rabbit. The specimens were excised at the 4th, 8th, 12th week, examined grossly analyzed by haematoxylin cosine, toluidine blues staining and type II collagen immunohistochemistry reaction. Wakitani score was counted to evaluate the repairing effect. RESULTS: Grossly analysis showed some ivory tissue filled the caves after 4 weeks and the caves were full filled with smooth surface after 12 weeks. The microscope showed a good deal of chondrocytes appeared after 8 weeks and more type II collagen than 4 weeks. Twelve weeks later, cartilage lacuna could be observed. The cells arrangement and the amount of type II collagen both showed the same as the natural one. CONCLUSION: Complicated material of fibrin glue and DBM as scaffolds can be used as scaffolds for cartilage tissue engineering. PMID: 19705719 [PubMed - in process] | |
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