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| Integration column: biofunctional polymeric nanoparticles for spatio-temporal control of drug delivery and biomedical applications.
March 11, 2010 at 7:12 AM
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| | Integration column: biofunctional polymeric nanoparticles for spatio-temporal control of drug delivery and biomedical applications. Integr Biol (Camb). 2009 Jul;1(7):446-51 Authors: Rothenfluh DA, Hubbell JA Polymeric nanoparticle technology has evolved from drug carrier design to advanced multifunctional macromolecular structures. They enable drug delivery and release of a bioactive under spatio-temporal control rather than just passive release by a long-circulating carrier. As such, the carrier is enabling the biomolecule or the bioactive to carry out its designed biological function. Due to their small size nanoparticles may also induce perturbations of biological systems different from any other biomaterials, therefore opening up new biomedical applications as well as raising concerns about adverse effects. PMID: 20023754 [PubMed - indexed for MEDLINE] | | |
| Hematopoietic stem and progenitor cells in adhesive microcavities.
March 11, 2010 at 7:12 AM
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| | Hematopoietic stem and progenitor cells in adhesive microcavities. Integr Biol (Camb). 2009 Jun;1(5-6):427-34 Authors: Kurth I, Franke K, Pompe T, Bornhäuser M, Werner C The homeostasis of hematopoietic stem and progenitor cells (HSC) in the bone marrow is regulated by a complex interplay of exogenous signals, including extracellular matrix (ECM) molecules, cell-cell contacts, and cytokines. To investigate the influence of spatial restriction and adhesive interactions on HSC fate decisions, we prepared a set of fibronectin-coated micrometer-sized cavities. Analysis of human CD133+ HSCs isolated after culture on these surfaces revealed that proliferation and differentiation is decreased when HSCs are supported by substrates with small microcavities. Single cell analysis of adherent cells also revealed decreased DNA synthesis and higher levels of HSC marker expression inside the smaller cavities. Increasing the cytokine concentration highlighted the tight balance of adhesion related signals and soluble cues acting on HSC fate decisions. Our results suggest that confining human HSCs in ECM-coated microcavities is a possible method to! maintain these cells in a quiescent and immature state, an important advantage for several HSC applications. PMID: 20023748 [PubMed - indexed for MEDLINE] | | |
| Integration column: artificial ECM: expanding the cell biology toolbox in 3D.
March 11, 2010 at 7:12 AM
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| | Integration column: artificial ECM: expanding the cell biology toolbox in 3D. Integr Biol (Camb). 2009 Mar;1(3):235-41 Authors: Lutolf MP Many crucial cellular processes in our tissues are governed by complex, spatio-temporally regulated interactions between cells and their extracellular matrix (ECM). These interactions can be studied using well-established 3D in vitro model systems such as collagen gels or Matrigel generated from native ECM macromolecular components. Recent advances in the molecular design of 'smart' synthetic biomaterials have generated artificial ECM (aECM) that mimic some of the key structural and biochemical characteristics of their naturally derived counterparts and, thanks to their synthetic origin, promise to overcome some complexities of the latter. Here I will discuss emerging approaches in aECM design, hopefully inspiring cell biologists to apply these systems to address their specific biological question. PMID: 20023734 [PubMed - indexed for MEDLINE] | | |
| Prefabrication of tissue engineered bone grafts: an experimental study.
March 11, 2010 at 7:12 AM
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| | Prefabrication of tissue engineered bone grafts: an experimental study. Ann Plast Surg. 2010 Jan;64(1):98-104 Authors: Okuda T, Uysal AC, Tobita M, Hyakusoku H, Mizuno H The purpose of this study was to determine whether angiogenesis could successfully be induced into bone tissue that was engineered by cultured adipose-derived stem cells with porous beta-tricalcium phosphate and whether its biologic properties could be maintained by flap prefabrication technique.Adipose-derived stem cells with porous beta-tricalcium phosphate were implanted into the superficial inferior epigastric artery flap of the Fisher rats. After prefabrication for 8 weeks, the prefabricated flaps were elevated and the pedicles were clamped for 4 hours. The samples were harvested after 2 weeks for analyses.Angiogenesis was significantly increased in the prefabricated groups (P < 0.05). There was no significant difference between the prefabricated and nonprefabricated groups in terms of the osteogenic capacity (P > 0.5).The promising results obtained with prefabrication in tissue engineered bone grafts encourage the clinical application of this technolog! y. Thus, prefabrication may be a useful technique in any engineered bone tissue transfer. PMID: 20010414 [PubMed - indexed for MEDLINE] | | |
| Hyalomatrix PA in burn care practice: results from a national retrospective survey, 2005 to 2006.
March 11, 2010 at 7:12 AM
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| | Hyalomatrix PA in burn care practice: results from a national retrospective survey, 2005 to 2006. Ann Plast Surg. 2010 Jan;64(1):69-79 Authors: Gravante G, Sorge R, Merone A, Tamisani AM, Di Lonardo A, Scalise A, Doneddu G, Melandri D, Stracuzzi G, Onesti MG, Cerulli P, Pinn R, Esposito G Results of a national retrospective survey on Hyalomatrix PA in burn patients are reported.A total of 11 burn centers were contacted.A total of 57 patients were available. Hyalomatrix PA was used on young and adult patients, mainly in deep partial thickness and full thickness burns. In most cases, Hyalomatrix PA was applied immediately after the wound cleaning (wound debridement or escharectomy for adults, dermabrasion or debridement in young patients). After 7 days, reepithelization processes were more frequent in deep partial thickness burns. One-half of the patient population underwent grafting. After 29 days, complete closure was achieved in almost all patients. The Vancouver Scar Scale showed better values for adults, while no differences were observed for burn depth or patients undergoing grafting. No adverse reactions were recorded.Hyalomatrix PA is used in young and adults, in deep partial thickness and full thickness burns, as a temporary coverage before ! grafting or alone for wound healing. PMID: 20010411 [PubMed - indexed for MEDLINE] | | |
| Differential expression of a novel gene BRE (TNFRSF1A modulator/BRCC45) in response to stress and biological signals.
March 11, 2010 at 7:12 AM
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| | Differential expression of a novel gene BRE (TNFRSF1A modulator/BRCC45) in response to stress and biological signals. Mol Biol Rep. 2010 Jan;37(1):363-8 Authors: Chan JY, Li L, Miao J, Cai DQ, Lee KK, Chui YL Stress-responsive genes play critical roles in many biological functions that includes apoptosis, survival, differentiation and regeneration. We have identified a novel stress-responsive gene called BRE which interacts with TNF-receptor-1 and blocks the apoptotic effect of TNF-alpha. BRE enhances tumor growth in vivo and is up-regulated in hepatocellular and esophageal carcinomas. BRE also regulates the ubiquitination of the DNA repair complex BRCC, and the synthesis of steroid hormones. Here, we examined BRE-mRNA in cells after treatments with UV and ionizing radiation (IR). UV and IR treatment alone suppressed BRE-mRNA levels by more than 90% at 24 h, while hydroxyurea, fluorodeoxyuridine, aphidicolin, known inhibitors of S-phase DNA synthesis, had no significant effect. BRE protein expression was unaltered in cells treated with TNF-alpha, Interleukin-1 and Dexamethasone, while a threefold increase was observed following chorionic gonadotropin exposure. Although! BRE plays a regulatory role in many different pathways, yet its expression is apparently under very stringent control. PMID: 19757177 [PubMed - indexed for MEDLINE] | | |
| Multiple functionalities of polyelectrolyte multilayer films: new biomedical applications.
March 11, 2010 at 7:12 AM
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| | Multiple functionalities of polyelectrolyte multilayer films: new biomedical applications. Adv Mater. 2010 Jan 26;22(4):441-67 Authors: Boudou T, Crouzier T, Ren K, Blin G, Picart C The design of advanced functional materials with nanometer- and micrometer-scale control over their properties is of considerable interest for both fundamental and applied studies because of the many potential applications for these materials in the fields of biomedical materials, tissue engineering, and regenerative medicine. The layer-by-layer deposition technique introduced in the early 1990s by Decher, Moehwald, and Lvov is a versatile technique, which has attracted an increasing number of researchers in recent years due to its wide range of advantages for biomedical applications: ease of preparation under "mild" conditions compatible with physiological media, capability of incorporating bioactive molecules, extra-cellular matrix components and biopolymers in the films, tunable mechanical properties, and spatio-temporal control over film organization. The last few years have seen a significant increase in reports exploring the possibilities offered by diffusin! g molecules into films to control their internal structures or design "reservoirs," as well as control their mechanical properties. Such properties, associated with the chemical properties of films, are particularly important for designing biomedical devices that contain bioactive molecules. In this review, we highlight recent work on designing and controlling film properties at the nanometer and micrometer scales with a view to developing new biomaterial coatings, tissue engineered constructs that could mimic in vivo cellular microenvironments, and stem cell "niches." PMID: 20217734 [PubMed - in process] | | |
| Advances in biomimetic and nanostructured biohybrid materials.
March 11, 2010 at 7:12 AM
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| | Advances in biomimetic and nanostructured biohybrid materials. Adv Mater. 2010 Jan 19;22(3):323-36 Authors: Ruiz-Hitzky E, Darder M, Aranda P, Ariga K The rapid increase of interest in the field of biohybrid and biomimetic materials that exhibit improved structural and functional properties is attracting more and more researchers from life science, materials science, and nanoscience. Concomitant results offer valuable opportunities for applications that involve disciplines dealing with engineering, biotechnology, medicine and pharmacy, agriculture, nanotechnology, and others. In the current contribution we collect recent illustrative examples of assemblies between materials of biological origin and inorganic solids of different characteristics (texture, structure, and particle size). We introduce here a general overview on strategies for the preparation and conformation of biohybrids, the synergistic effects that determine the final properties of these materials, and their diverse applications, which cover areas as different as tissue engineering, drug delivery systems, biosensing devices, biocatalysis, green na! nocomposites, etc. PMID: 20217713 [PubMed - in process] | | |
| Dendritic polyglycerols for biomedical applications.
March 11, 2010 at 7:12 AM
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| | Dendritic polyglycerols for biomedical applications. Adv Mater. 2010 Jan 12;22(2):190-218 Authors: Calderón M, Quadir MA, Sharma SK, Haag R The application of nanotechnology in medicine and pharmaceuticals is a rapidly advancing field that is quickly gaining acceptance and recognition as an independent area of research called "nanomedicine". Urgent needs in this field, however, are biocompatible and bioactive materials for antifouling surfaces and nanoparticles for drug delivery. Therefore, extensive attention has been given to the design and development of new macromolecular structures. Among the various polymeric architectures, dendritic ("treelike") polymers have experienced an exponential development due to their highly branched, multifunctional, and well-defined structures. This Review describes the diverse syntheses and biomedical applications of dendritic polyglycerols (PGs). These polymers exhibit good chemical stability and inertness under biological conditions and are highly biocompatible. Oligoglycerols and their fatty acid esters are FDA-approved and are already being used in a variety of ! consumer applications, e.g., cosmetics and toiletries, food industries, cleaning and softening agents, pharmaceuticals, polymers and polymer additives, printing photographing materials, and electronics. Herein, we present the current status of dendritic PGs as functional dendritic architectures with particular focus on their application in nanomedicine, in drug, dye, and gene delivery, as well as in regenerative medicine in the form of non-fouling surfaces and matrix materials. PMID: 20217684 [PubMed - in process] | | |
| Controlling stem cell fate with material design.
March 11, 2010 at 7:12 AM
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| | Controlling stem cell fate with material design. Adv Mater. 2010 Jan 12;22(2):175-89 Authors: Marklein RA, Burdick JA Advances in our understanding of stem cell interactions with their environment are leading to the development of new materials-based approaches to control stem cell behavior toward cellular culture and tissue regeneration applications. Materials can provide cues based on chemistry, mechanics, structure, and molecule delivery that control stem cell fate decisions and matrix formation. These approaches are helping to advance clinical translation of a range of stem cell types through better expansion techniques and scaffolding for use in tissue engineering approaches for the regeneration of many tissues. With this in mind, this progress report covers basic concepts and recent advances in the use of materials for manipulating stem cells. PMID: 20217683 [PubMed - in process] | | |
| Biosensing and drug delivery at the microscale : novel devices for controlled and responsive drug delivery.
March 11, 2010 at 7:12 AM
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| | Biosensing and drug delivery at the microscale : novel devices for controlled and responsive drug delivery. Handb Exp Pharmacol. 2010;(197):87-112 Authors: Robitzki AA, Kurz R An overall objective of pharmaceutical research is the controlled release or delivery of drugs at the biological target site in a therapeutically and pharmacodynamically optimal amount. In relation to "intelligent" drug delivery, several basic aspects are important, i.e., release of active pharmaceutical ingredients from the formulation, transport to and penetration across biological barriers, and subsequent biotransformation depending on a controlled release process. Future development of advanced and/or controlled drug releasing systems, e.g. polymeric or particulate drug targeting systems, nano-carbon tube related and/or nano-pillar based drug release, or electronically mediated molecule delivery, is expected to take advantage of progress in molecular cell biology, cell and tissue engineering, membrane nano-biophysics, and bioelectronic properties (Bramstedt et al. 2005; Gardner et al. 2006). In this chapter novel aspects of the development of innovative drug d! elivery systems described and are categorized into polymeric, lipid-based or electronically mediated delivery systems (De la Heras et al. 2004). PMID: 20217527 [PubMed - in process] | | |
| In Vivo Regeneration of Insulin-Producing beta-Cells.
March 11, 2010 at 7:12 AM
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| | In Vivo Regeneration of Insulin-Producing beta-Cells. Adv Exp Med Biol. 2010;654:627-40 Authors: Jun HS Type 1 and type 2 diabetes mellitus are considered to be caused by defective control of blood glucose resulting from a reduced beta-cell mass. Thus, the restoration of a functional beta-cell mass by replacing the damaged beta-cells or stimulating beta-cell regeneration is a logical approach for the treatment of diabetes. Strategies for increasing the beta-cell mass include stimulating beta-cell replication and differentiation and inhibiting beta-cell death. Treatment with various growth factors such as GLP-1, BTC, HGF, and EGF and forced expression of beta-cell transcription factors such as Pdx-1, NeuroD, and MafA resulted in the regeneration of beta-cells in vivo. Another approach is the administration of stem/progenitor cells, which can differentiate into insulin-producing cells. However, there are no satisfactory methods yet for clinical application. Understanding the mechanisms of the regenerative process of pancreatic beta-cells will pave the way for the deve! lopment of regenerative medicine for treatment of diabetes. PMID: 20217517 [PubMed - in process] | | |
| Islet cell development.
March 11, 2010 at 7:12 AM
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| | Islet cell development. Adv Exp Med Biol. 2010;654:59-75 Authors: Rojas A, Khoo A, Tejedo JR, Bedoya FJ, Soria B, Martín F Over the last years, there has been great success in driving stem cells toward insulin-expressing cells. However, the protocols developed to date have some limitations, such as low reliability and low insulin production. The most successful protocols used for generation of insulin-producing cells from stem cells mimic in vitro pancreatic organogenesis by directing the stem cells through stages that resemble several pancreatic developmental stages. Islet cell fate is coordinated by a complex network of inductive signals and regulatory transcription factors that, in a combinatorial way, determine pancreatic organ specification, differentiation, growth, and lineage. Together, these signals and factors direct the progression from multipotent progenitor cells to mature pancreatic cells. Later in development and adult life, several of these factors also contribute to maintain the differentiated phenotype of islet cells. A detailed understanding of the processes that ope! rate in the pancreas during embryogenesis will help us to develop a suitable source of cells for diabetes therapy. In this chapter, we will discuss the main transcription factors involved in pancreas specification and beta-cell formation. PMID: 20217494 [PubMed - in process] | | |
| Tensile Strain as a Regulator of Mesenchymal Stem Cell Osteogenesis.
March 11, 2010 at 7:12 AM
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| | Tensile Strain as a Regulator of Mesenchymal Stem Cell Osteogenesis. Ann Biomed Eng. 2010 Mar 9; Authors: Kearney EM, Farrell E, Prendergast PJ, Campbell VA A role for mechanical stimulation in the control of cell fate has been proposed and mechanical conditioning of mesenchymal stem cells (MSCs) is of interest in directing MSC behavior for tissue engineering applications. This study investigates strain-induced differentiation and proliferation of MSCs, and investigates the cellular mechanisms of mechanotransduction. MSCs were seeded onto a collagen-coated silicone substrate and exposed to cyclic tensile mechanical strain of 2.5% at 0.17 Hz for 1-14 days. To examine mechanotransduction, cells were strained in the presence of the stretch-activated cation channel (SACC) blocker, gadolinium chloride (GdCl(3)); the extracellular regulated kinase (ERK) inhibitor, U0126; the p38 inhibitor, SB203580; and the phosphatidylinosito1 3-kinase (PI3-kinase) inhibitor, LY294002. Following exposure to strain, the osteogenic markers Cbfalpha1, collagen type I, osteocalcin, and BMP2 were temporally expressed. Exposure to strain in the ! presence of GdCl(3) (10 muM) reduced the induction of collagen I expression, thus identifying a role for SACC, at least in part, as mechanosensors in strain-induced MSC differentiation. The strain-induced synthesis of BMP2 was found to be reduced by inhibitors of the kinases, ERK, p38, and PI3 kinase. Additionally, mechanical strain reduced the rate of MSC proliferation. The identification of the mechanical control of MSC proliferation and the molecular link between mechanical stimulation and osteogenic differentiation has consequences for regenerative medicine through the development of a functional tissue engineering approach. PMID: 20217480 [PubMed - as supplied by publisher] | | |
| Physicochemical properties and cytotoxicities of Sr-containing biphasic calcium phosphate bone scaffolds.
March 11, 2010 at 7:12 AM
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| | Physicochemical properties and cytotoxicities of Sr-containing biphasic calcium phosphate bone scaffolds. J Mater Sci Mater Med. 2010 Mar 10; Authors: Dagang G, Kewei X, Yaxiong L This study demonstrates a new biomaterial system composed of Sr-containing hydroxyapatite (Sr-HA) and Sr-containing tricalcium phosphate (Sr-TCP), termed herein Sr-containing biphasic calcium phosphate (Sr-BCP). Furthermore, a series of new Sr-BCP porous scaffolds with tunable structure and properties has also been developed. These Sr-BCP scaffolds were obtained by in situ sintering of a series of composites formed by casting various Sr-containing calcium phosphate cement (Sr-CPC) into different rapid prototyping (RP) porous phenol formaldehyde resins, which acted as the negative moulds for controlling pore structures of the final scaffolds. Results show that the porous Sr-BCP scaffolds are composed of Sr-HA and Sr-TCP. The phase composition and the macro-structure of the Sr-BCP scaffold could be adjusted by controlling the processing parameters of the Sr-CPC pastes and the structure parameters of the RP negative mould, respectively. It is also found that both the! compressive strength (CS) and the dissolving rate of the Sr-BCP scaffold significantly vary with their phase composition and macropore percentage. In particular, the compressive strength achieves a maximum CS level of 9.20 +/- 1.30 MPa for the Sr-BCP scaffold with a Sr-HA/Sr-TCP weight ratio of 78:22, a macropore percentage of 30% (400-550 mum in size) and a total-porosity of 63.70%, significantly higher than that of the Sr-free BCP scaffold with similar porosity. All the extracts of the Sr-BCP scaffold exhibit no cytotoxicity. The current study shows that the incorporation of Sr plays an important role in positively improving the physicochemical properties of the BCP scaffold without introducing obvious cytotoxicity. It also reveals a potential clinical application for this material system as bone tissue engineering (BTE) scaffold. PMID: 20217190 [PubMed - as supplied by publisher] | | |
| Rapid generation of biologically relevant hydrogels containing long-range chemical gradients.
March 11, 2010 at 7:12 AM
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| | Rapid generation of biologically relevant hydrogels containing long-range chemical gradients. Adv Funct Mater. 2010;20(1):131-137 Authors: He J, Du Y, Villa-Uribe JL, Hwang C, Li D, Khademhosseini A Many biological processes are regulated by gradients of bioactive chemicals. Thus, the generation of materials with embedded chemical gradients may be beneficial for understanding biological phenomena and generating tissue-mimetic constructs. Here we describe a simple and versatile method to rapidly generate materials containing centimeter-long gradients of chemical properties in a microfluidic channel. The formation of chemical gradient was initiated by a passive-pump-induced forward flow and further developed during an evaporation-induced backward flow. The gradient was spatially controlled by the backward flow time and the hydrogel material containing the gradient was synthesized via photopolymerization. Gradients of a cell-adhesion ligand, Arg-Gly-Asp-Ser (RGDS), was incorporated in the poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels to test the response of endothelial cells. The cells attached and spread along the hydrogel material in a manner consistent ! with the RGDS gradient profile. A hydrogel containing PEG-DA concentration gradient and constant RGDS concentration was also generated. The morphology of cells cultured on such hydrogel changed from round in the lower PEG-DA concentration regions to well-spread in the higher PEG-DA concentration regions. This approach is expected to be a valuable tool to investigate the cell-material interactions in a simple and high-throughput manner and to design graded biomimetic materials for tissue engineering applications. PMID: 20216924 [PubMed - as supplied by publisher] | | |
| Frequent Endonuclease Cleavage at Off-target Locations In Vivo.
March 11, 2010 at 7:12 AM
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| | Frequent Endonuclease Cleavage at Off-target Locations In Vivo. Mol Ther. 2010 Mar 9; Authors: Petek LM, Russell DW, Miller DG Target-site DNA breaks increase recombination frequencies, however, the specificity of the enzymes used to create them remains poorly defined. The location and frequency of off-target cleavage events are especially important when rare-cutting endonucleases are used in clinical settings. Here, we identify noncanonical cleavage sites of I-SceI that are frequently cut in the human genome by localizing adeno-associated virus (AAV) vector-chromosome junctions, demonstrating the importance of in vivo characterization of enzyme cleavage specificity. PMID: 20216527 [PubMed - as supplied by publisher] | | |
| Isolation of Mesenchymal Stem Cells with Neurogenic Potential from the Mesoderm of the Amniotic Membrane.
March 11, 2010 at 7:12 AM
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| | Isolation of Mesenchymal Stem Cells with Neurogenic Potential from the Mesoderm of the Amniotic Membrane. Cells Tissues Organs. 2010 Mar 9; Authors: Chang YJ, Hwang SM, Tseng CP, Cheng FC, Huang SH, Hsu LF, Hsu LW, Tsai MS The amniotic membrane has been clinically applied as a therapeutic material in wound covering and corneal surface reconstruction. Recently, mesenchymal stem cells (MSCs) have been isolated from the placenta, specifically from the amniotic membrane. However, the localization of MSCs in the amniotic membrane has not been determined. In this study, term placenta was collected, and we performed immunohistochemical staining techniques to identify and localize MSCs in the mesoderm of the amniotic membrane in situ with MSC antibodies, including CD90 and CD105. We further directly cultured and characterized MSCs from the amniotic membrane mesoderm (AMSCs). The AMSCs were easily isolated and represented a homogenous fibroblastic morphology at early passages. In addition to MSC surface markers, AMSCs expressed Sox2, Oct-4 and Nanog. AMSCs could be induced into osteocytes, adipocytes and chondrocytes in vitro and show immunosuppressive effects on T-cell proliferation. Under ! appropriate conditions, AMSCs could differentiate into neuronal-like cells, which were identified by neuronal-specific markers and their ability to secrete dopamine. This study reveals that AMSCs provide a promising source for stem cell studies and also extend the clinical potential of the amniotic membrane in the field of regenerative medicine. PMID: 20215735 [PubMed - as supplied by publisher] | | |
| HDL/Apolipoprotein A-I Binds to Macrophage-Derived Progranulin and Suppresses its Conversion into Proinflammatory Granulins.
March 11, 2010 at 7:12 AM
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| | HDL/Apolipoprotein A-I Binds to Macrophage-Derived Progranulin and Suppresses its Conversion into Proinflammatory Granulins. J Atheroscler Thromb. 2010 Mar 9; Authors: Okura H, Yamashita S, Ohama T, Saga A, Yamamoto-Kakuta A, Hamada Y, Sougawa N, Ohyama R, Sawa Y, Matsuyama A Aim: HDL has anti-inflammatory effects on macrophages, although the mechanism of action remains unclear. We hypothesized that HDL suppresses the conversion of macrophage-secreted factors into proinflammatory factors via binding, and tried to identify the factor that could form a complex with HDL and/or apolipoprotein (apo) A-I.Methods and Results: In conditioned media obtained from human monocyte-derived macrophages, we found an apo A-I binding protein and identified the protein as progranulin/proepithelin/acrogranin/PCDGF. Co-immunoprecipitation analysis showing that progranulin binds and forms a complex with apo A-I and the presence of progranulin in the HDL fraction in the sera indicated that progranilin is a novel apolipoprotein. Conditioned media of HEK293 cells transfected with progranulin augmented the expression of TNF-alpha and IL-1-beta on macrophages, but these effects of progranulin were inhibited by co-incubation with HDL or apo A-I. Anti-progranulin ! antibodies also reduced the expression of TNF-alpha and IL-1-beta on macrophages. Granulins as conversion products derived from progranilin increased TNF-alpha and IL-1-beta expression and the effects were not suppressed by HDL.Conclusions: Our results suggest that the anti-inflammatory effects of HDL on macrophages might be due to suppression of the conversion of progranulin into proinflammatory granulins by forming a complex. PMID: 20215705 [PubMed - as supplied by publisher] | | |
| Episodes of Prolactin Gene Expression in GH3 Cells Are Dependent on Selective Promoter Binding of Multiple Circadian Elements.
March 11, 2010 at 7:12 AM
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| | Episodes of Prolactin Gene Expression in GH3 Cells Are Dependent on Selective Promoter Binding of Multiple Circadian Elements. Endocrinology. 2010 Mar 9; Authors: Bose S, Boockfor FR Prolactin (PRL) gene expression in mammotropes occurs in pulses, but the mechanism(s) underlying this dynamic process remains obscure. Recent findings from our laboratory of an E-box in the rat PRL promoter (E-box133) that can interact with the circadian factors, circadian locomoter output cycles kaput (CLOCK) and brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1, and was necessary for pulse activity raised the intriguing possibility that the circadian system may be central to this oscillatory process. In this study, we used serum-shocked GH3 cells, established previously to synchronize PRL pulses between cells in culture, to reveal that pulses of PRL mRNA are linked temporally to the expression of bmal1, cry1, per1, and per3 mRNA in these cells. Moreover, we found that each of these circadian factors binds to the rat PRL promoter by chromatin immunoprecipitation analysis. Using EMSA analysis, we observed that two sites present ! in the proximal promoter region, E-box133 and E-box10, bind circadian factors differentially (E-box133 interacted with BMAL1, cryptochrome-1, period (PER)-1, and PER3 but not PER2 and E-box10 bound BMAL1, cryptochrome-1, PER2, PER3 but not PER1). More importantly, down-regulation of any factor binding E-box133 significantly reduced PRL mRNA levels during pulse periods. Our results demonstrate clearly that certain circadian elements binding to the E-box133 site are required for episodes of PRL mRNA expression in serum-shocked GH3 cultures. Moreover, our findings of binding-related differences between functionally distinct E-boxes demonstrate not only that E-boxes can bind different components but suggest that the number and type of circadian elements that bind to an E-box is central in dictating its function. PMID: 20215567 [PubMed - as supplied by publisher] | | |
| Evaluation of Nanostructural, Mechanical and Biological Properties of Collagen-Nanotube Composites.
March 11, 2010 at 7:12 AM
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| | Evaluation of Nanostructural, Mechanical and Biological Properties of Collagen-Nanotube Composites. IEEE Trans Nanobioscience. 2010 Mar 8; Authors: Tan W, Twomey J, Guo D, Madhavan K, Li M Collagen I is an essential structural and mechanical building block of various tissues, and it is often used as tissue engineering scaffolds. However, collagenbased constructs reconstituted in vitro often lack robust fiber structure, mechanical stability and molecule binding capability. To enhance these performances, the present study developed three-dimensional collagen-nanotube composite constructs with two types of functionalized carbon nanotubes, carboxylated nanotubes and covalently-functionalized nanotubes (CFNT). The influences of nanotube functionalization and loading concentration on the collagen fiber structure, mechanical property, biocompatibility and molecule binding were examined. Results revealed that surface modification and loading concentration of nanotubes determined the interactions between nanotubes and collagen fibrils, thus altering the structure and property of nanotube-collagen composites. Scanning electron microscopy and confocal microsco! py revealed that the incorporation of CFNT in collagen-based constructs was an effective means of restructuring collagen fibrils because CFNT strongly bound to collagen molecules inducing the formation of larger fibril bundles. However, increased nanotube loading concentration caused the formation of denser fibril network and larger aggregates. Static stress-strain tests under compression showed that the addition nanotube into collagen-based constructs did not significantly increase static compressive moduli. Creep/recovery testing under compression revealed that CFNT-collagen constructs showed improved mechanical stability under continuous loading. Testing with endothelial cells showed that biocompatibility was highly dependent on nanotube loading concentration. At a low loading level, CFNT-collagen showed higher endothelial coverage than the other tested constructs or materials. Additionally, CFNT-collagen showed capability of binding to other biomolecules to enhance the ! construct functionality. In conclusion, functionalized nanotub! e-collag en composites, particularly CFNT-collagen composites, could be promising materials which provide structural support showing bundled fibril structure, biocompatibility, multi-functionality and mechanical stability, but rigorous control over chemical modification, loading concentration and nanotube dispersion are needed. PMID: 20215088 [PubMed - as supplied by publisher] | | |
| Fabrication of porous polysaccharide-based scaffolds using a combined freeze-drying/cross-linking process.
March 11, 2010 at 7:12 AM
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| | Fabrication of porous polysaccharide-based scaffolds using a combined freeze-drying/cross-linking process. Acta Biomater. 2010 Mar 4; Authors: Autissier A, Visage CL, Pouzet C, Chaubet F, Letourneur D Biocompatible three-dimensional porous scaffolds are of great interest for tissue engineering applications. We present here a novel combined freeze-drying/cross-linking process to prepare porous polysaccharide-based scaffolds. This process does not require organic solvent nor porogen agent. We unexpectedly found that cross-linking of biomacromolecules such as pullulan and dextran with sodium trimetaphosphate could be performed during a freeze-drying process. We evidenced that the freeze-drying pressures modulate the degree of porosity. High freeze-drying pressure scaffolds presented pores with a mean diameter of 55+/-4 microns and a porosity of 33%+/-12%, whereas low freeze-drying pressure scaffolds contained larger pores with a mean diameter of 243+/-14 microns and a porosity of 68%+/-3%. The porous scaffolds could be easily obtained at the desired shape and were stable in culture medium for weeks. In vitro, viable mesenchymal stem cells were found associated wit! h porous scaffolds in higher proportions than with non-porous scaffolds. Moreover, cells penetrated deeper into scaffolds with larger pores. This novel combined freeze-drying/cross-linking process of polysaccharides enabled the fabrication of biocompatible scaffolds with controlled porosity and architecture suitable for 3D in vitro culture and biomedical applications. PMID: 20215057 [PubMed - as supplied by publisher] | | |
| Cellular cardiomyoplasty and cardiac tissue engineering for myocardial therapy.
March 11, 2010 at 7:12 AM
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| | Cellular cardiomyoplasty and cardiac tissue engineering for myocardial therapy. Adv Drug Deliv Rev. 2010 Mar 6; Authors: Wang F, Guan J Heart diseases, including myocardial infarction (MI) and congestive heart failure (CHF), have high mortality rates. Both MI and CHF are characterized by cardiac muscle damage caused by massive cardiomyocyte death and reduced cardiac function. Cellular therapy aimed at using cells to improve cardiac function and/or regenerate new myocardium, has been extensively investigated for cardiac repair. Two strategies have been currently taken for cellular transplantation, including in situ cellular cardiomyoplasty and cardiac tissue engineering. The in situ cellular cardiomyoplasty strategy delivers cells directly into the infarcted myocardium. A variety of cell types has been shown to be beneficial in cardiac repair. However, this strategy is limited in terms of cell retention, survival of the engrafted cells, cell differentiation, and integration of transplanted cells with host tissue. Cardiac tissue engineering is an alternate strategy to in situ cellular cardiomyoplast! y, which is designed to repair infarcted myocardium using cells, biomaterials and regulative factors (for example growth factors). There are currently various approaches for cardiac tissue engineering, such as, in situ delivering cells with injectable biomaterials into the infarcted myocardium, in vitro engineering of contractile tissue constructs followed by in vivo implantation, in vitro engineering of stem cell loaded tissue constructs for in vivo myocardium regeneration, and cell sheet tissue engineering. This review provides a comprehensive progress of in situ cellular cardiomyoplasty and cardiac tissue engineering for cardiac repair. PMID: 20214939 [PubMed - as supplied by publisher] | | |
| Use of Tissue Engineering in Treatment of the Male Genitourinary Tract Abnormalities.
March 11, 2010 at 7:12 AM
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| | Use of Tissue Engineering in Treatment of the Male Genitourinary Tract Abnormalities. J Sex Med. 2010 Feb 25; Authors: Fu Q, Cao YL ABSTRACT Introduction. A variety of congenital and acquired male genitourinary tract abnormalities can lead to organ damage or tissue loss that requires surgical reconstruction. Traditional reconstructive methods do not produce consistent satisfactory structural or functional replacement and may damage the genitourinary tract. Tissue engineering provides a promising alternative for the treatment of these disorders. Aim. The aim of this article is to provide an update on clinical and experimental evidence concerning the application of tissue engineering to treatment of abnormalities in the male genitourinary tract system. Methods. A PubMed search was performed to retrieve relevant clinical and basic literature. Main Outcome Measures. The topics discussed in this review include the experimental and clinical application of tissue engineering for reconstruction of the urethra, penis, testis, and prostate. Results. Tissue engineering techniques can provide a plentiful ! source of healthy tissue for reconstructive purposes. Acellular matrix scaffold and seed cells are two key elements in tissue engineering. Proper employment of seed cells and scaffold material may result in synergistic effects. Moreover, new tissue engineering technologies are being transferred from the laboratory to clinical practice. Conclusions. Tissue engineering provides biological substitutes that can restore and maintain normal function in diseased and injured tissues, thus providing an effective technique for regeneration of the male genitourinary tract. Fu Q, and Cao Y. Use of tissue engineering in treatment of the male genitourinary tract abnormalities. J Sex Med **;**:**-**. PMID: 20214721 [PubMed - as supplied by publisher] | | |
| Human Embryonic and Induced Pluripotent Stem Cells in Basic and Clinical Research in Cardiology.
March 11, 2010 at 7:12 AM
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| | Human Embryonic and Induced Pluripotent Stem Cells in Basic and Clinical Research in Cardiology. Curr Stem Cell Res Ther. 2010 Mar 8; Authors: Blin G, Neri T, Stefanovic S, Pucéat M Human Embryonic or pluripotent stem cells hold many promises in regenerative medicine. They also provide the scientific community with powerful models of early human development including cardiogenesis under normal or pathological (congenital and genetic diseases) situations. Furthermore their cardiac derivatives turn out to be very useful to study human cardiac electrophysiology, pharmacology or cardiac toxicology. The current overview provides the basic knowledge on developmental biology of the heart which can be applied to stem cell research to study early cardiogenesis. We summarize both the cardiogenic transcriptional network and the role of morphogens involved in early cardiogenesis. We review protocols of cardiac differentiation of pluripotent stem cells so far available. We finally discuss the translation of basic stem cell research into clinical applications. PMID: 20214559 [PubMed - as supplied by publisher] | | |
| Tissue-Engineered 3-D Tumor Models to Study Tumor Angiogenesis.
March 11, 2010 at 7:12 AM
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| | Tissue-Engineered 3-D Tumor Models to Study Tumor Angiogenesis. Tissue Eng Part A. 2010 Mar 9; Authors: Verbridge SS, Chandler EM, Fischbach-Teschl C Cell-microenvironment interactions play a critical role in the transformation of normal cells into cancer; however, the underlying mechanisms and effects are far from being well understood. Tissue Engineering provides innovative culture tools and strategies to study tumorigenesis under pathologically relevant culture conditions. Specifically, integration of biomaterials, scaffold fabrication, and micro/nano-fabrication techniques offers great promise to reveal the dynamic role of chemical, cell-cell, cell-extracellular matrix, and mechanical interactions in the pathogenesis of cancer. Due to the central importance of blood vessel formation in tumor growth, progression, and drug response, this review will discuss specific design parameters for the development of culture microenvironments to study tumor angiogenesis. Tumor Engineering approaches have the potential to revolutionize our understanding of cancer, provide new platforms for testing of anti-cancer drugs, a! nd may ultimately result in improved treatment strategies. PMID: 20214471 [PubMed - as supplied by publisher] | | |
| Microfluidic culture models of tumor angiogenesis.
March 11, 2010 at 7:12 AM
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| | Microfluidic culture models of tumor angiogenesis. Tissue Eng Part A. 2010 Mar 9; Authors: Fischbach-Teschl C, Stroock A Blood vessels control all stages of tumor development and therapy by defining the physicochemical and cellular state of the tumor microenvironment. However, no pathologically relevant culture systems currently exist that recapitulate the associated cellular and convective mass transfer processes that are implicated in tumor angiogenesis. By integrating tissue engineering and microfluidic technologies it will be possible to develop tumor-mimetic culture environments with embedded microvascular structures. Utilization of these microfluidic tumor models will help reveal the importance of the transport of chemical and cellular factors in tumor angiogenesis, and provide a test bed that may ultimately improve current strategies to anti-angiogenic therapy. PMID: 20214470 [PubMed - as supplied by publisher] | | |
| Enzymatically Crosslinked Dextran-tyramine Hydrogels as Injectable Scaffolds for Cartilage Tissue Engineering.
March 11, 2010 at 7:12 AM
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| | Enzymatically Crosslinked Dextran-tyramine Hydrogels as Injectable Scaffolds for Cartilage Tissue Engineering. Tissue Eng Part A. 2010 Mar 9; Authors: Jin R, Moreirateixeira LS, Dijkstra P, Zhong Z, van Blitterswijk C, Karperien M, Feijen J Enzymatic crosslinking of dextran-tyramine (Dex-TA) conjugates in the presence of horseradish peroxidase and hydrogen peroxide was successively applied in the preparation of hydrogels. Depending on the molecular weight of the dextran (Mn, GPC of 14000 or 31000 g/mol) and the degree of substitution (DS of 5, 10 or 15) with tyramine (TA) groups, the gelation times ranged from 20 s to 1 min. Hydrogels prepared from Dex31k -TA with a DS of 10 had storage moduli up to 60 kPa. Similar values were found when chondrocytes were incorporated into the hydrogels. Chondrocyte-seeded Dex-TA hydrogels were prepared at a molar ratio of H2O2/TA of 0.2 and cultured in a chondrocyte medium. A live-dead assay and a MTT assay revealed that almost all chondrocytes retained their viability after 2 weeks. SEM analysis showed that the encapsulated chondrocytes were capable of maintaining their round shape. Histology and immunofluorescent staining demonstrated the production of glycosamino! glycans (GAGs) and collagen type II after culturing for 14 and 21 days. Biochemical analysis showed that GAG accumulation increased with time inside Dex-TA hydrogels. Besides, GAG/DNA for Dex-TA hydrogels was higher than that for agarose at day 28. These results indicate that Dex-TA hydrogels are promising 3D scaffolds for cartilage tissue engineering applications. PMID: 20214454 [PubMed - as supplied by publisher] | | |
| Constructing Kidney-like Tissues from Cells Based on Programs for Organ Development: Towards a Method of In Vitro Engineering of the Kidney.
March 11, 2010 at 7:12 AM
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| | Constructing Kidney-like Tissues from Cells Based on Programs for Organ Development: Towards a Method of In Vitro Engineering of the Kidney. Tissue Eng Part A. 2010 Mar 9; Authors: Rosines E, Johkura K, Zhang X, Schmidt HJ, Decambre M, Bush KT, Nigam S The plausibility of constructing vascularized 3-dimensional kidney tissue from cells was investigated. The kidney develops from mutual inductive interactions between cells of the ureteric bud (UB), derived from the Wolffian duct, (WD), and the metanephric mesenchyme (MM). Isolated MMs were capable of inducing branching morphogenesis in WD tissue in recombination cultures, indicating that the isolated MM retains inductive capacity for cells other than the UB. Hanging drop aggregates of embryonic and adult renal epithelial cells (UB and mIMCD cells) were capable of inducing MM epithelialization and tubulogenesis with apparent connections (UB cells) and collecting duct-like tubules with lumens (mIMCD cells), supporting the view that the collecting system can be constructed from renal epithelial cells when stimulated by MM. Although the functions of the MM could not be replaced by cultured mesenchymal cells, primary MM cells and one MM-derived cell line (BSN) produced! factors that stimulate branching morphogenesis, whereas another, RIMM-18, supported WD budding as a feeder layer. While engineering of a kidney-like tissue from cultured cells alone remains to be achieved, these results suggest the feasibility of such an approach following the normal developmental progression of the UB and MM. Consistent with this notion, implants of kidney-like tissues constructed in vitro from recombinations of the UB and MM survived for over 5 weeks and achieved an apparently host-derived glomerular vasculature. Lastly, optimal macro and micro-patterning of kidney-like tissue is necessary for function of an organ assembled using a tissue engineering approach. To identify suitable conditions, 3D reconstructions of HoxB7-GFP mouse rudiments (E12) cultured on a filter or suspended in a collagen gel (type I or type IV), revealed that type IV collagen 3D culture supports the deepest tissue growth (600 +/- 8 mum) and the largest kidney volume (0.22 +/- 0.02 m! m3), and enabled the development of an umbrella-shaped collect! ing syst em such as occurs in vivo. Taken together with prior work (Rosines et al., 2007, Proc. Natl. Acad. Sci, USA, 104:20938; Steer et al., 2002, Kidney Int., 62:1958), these results support the plausibility of a developmental strategy for constructing vascularized 3D kidney-like tissues from recombinations of cultured renal progenitor cells. PMID: 20214453 [PubMed - as supplied by publisher] | | |
| Implication of silk film RGD availability and surface roughness on cytoskeletal organization and proliferation of primary rat bone marrow cells.
March 11, 2010 at 7:12 AM
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| | Implication of silk film RGD availability and surface roughness on cytoskeletal organization and proliferation of primary rat bone marrow cells. Tissue Eng Part A. 2010 Mar 9; Authors: Mandal BB, Das S, Chaudhury K, Kundu SC In order to design and fabricate next-generation tissue engineering materials, the understanding of cell responses to material surfaces is required. Surface topography presents powerful cues for cells and can strongly influence cell morphology, adhesion and proliferation but the mechanisms mediating this cell response remain unclear. In this report, we have investigated the effects of nanoroughness assemblies of silk fibroin protein membranes and RGD sequences fabricated from two different silk fibroin sources, i.e. mulberry (Bombyx mori) and non-mulberry (Antheraea mylitta) on cytoskeletal organization, proliferation and viability using primary rat bone marrow cells. To vary surface roughness, silk fibroin substrates were treated with graded ethanol (50 - 100 % v/v) to produce nanoarchitectures in the range of 1- 12 nm height. The graded alcohol treatments have been found to produce nanoscale topographies of reproducible height in a much faster and cheaper way. T! he results showed no difference in cell proliferation within the same treatment groups for both silk types. Though, a change in cell response in terms of good cytoskeleton organization, actin development, cell spreading and strong binding to substratum using A. mylitta fibroin protein films having RGD sequences was observed. This finding provides the information that the nanoroughness affects cellular processes in a cell specific manner and may be helpful for the development of ''smart'' silk based biomaterials especially for directing cell differentiation and regenerative therapies. PMID: 20214452 [PubMed - as supplied by publisher] | | |
| Experimental intervertebral disc regeneration with tissue engineered composite in a canine model.
March 11, 2010 at 7:12 AM
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| | Experimental intervertebral disc regeneration with tissue engineered composite in a canine model. Tissue Eng Part A. 2010 Mar 9; Authors: Ruan D, Xin H, Zhang C, Wang C, Xu C, Li C, He Q To construct PLGA scaffold-nucleus pulposus cells composite using tissue engineering methods and to investigate the in vivo performance of the composite in a canine model. Nucleus pulposus (NP) cells were isolated from the lumbar intervertebral discs of beagle dog. NP cells were cultured and expanded in vitro and seeded onto a 3-D porous poly (L-lactic-co-glycolic acid) (PLGA) scaffold. The composite was tested in 18 beagle dogs which were randomly divided into 3 groups: nucleotomy alone (A); nucleotomy with PLGA implantation(B), and nucleotomy with PLGA scaffold/NP cells composite implantation (C). X-ray and MRI scan were performed pre- and postoperatively. Evaluation of disc height, segment stability, biomechanics, and immunohistochemical analysis were performed. Dog NP cells could attach and showed proliferation activity within the PLGA scaffold in vitro and in vivo. The disc height, segmental stability and T2-weighted signal intensity on MRI were well preserve! d in group C dogs with engineered composite. PHK-26 positive cells were found within the area of the nucleus pulposus 8 weeks post operatively. The NP cell-PLGA scaffold composite can prevent or delay the degenerate process after nucleotomy in the canine model. This hybrid composite might be a promising construct for intervertebral disc regeneration. PMID: 20214451 [PubMed - as supplied by publisher] | | |
| Beyond Cell Capture: Antibody-conjugation Improves Haemocompatibility for Vascular Tissue Engineering Applications.
March 11, 2010 at 7:12 AM
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| | Beyond Cell Capture: Antibody-conjugation Improves Haemocompatibility for Vascular Tissue Engineering Applications. Tissue Eng Part A. 2010 Mar 9; Authors: Chong MS, Teoh SH, Teo EY, Zhang ZY, Lee CN, Koh SC, Choolani M, Chan J Antibody conjugated surfaces are being studied for cardiovascular implant applications to capture Endothelial Progenitor Cells (EPCs) and promote endothelialisation. However, despite the large amount of literature on EPC capture efficiency, little effort has been made to understand acute blood responses to the modified surfaces. We hypothesise that CD34 antibody conjugation passivates surfaces against pro-coagulatory events,and thus improves haemocompatibility. To test this hypothesis, we subjected the modified films to haemocompatibility tests to evaluate contact activation, platelet adhesion and activation, as well as whole blood clotting response to the films. Here, we demonstrate the alteration of blood responses due to polyacrylic acid (PAAc) engraftment and subsequent antibody conjugation on biaxially stretched polycaprolactone (muXPCL) films. Compared to muXPCL, PAAc engrafted PCL (PCL-PAAc) and CD34 antibody conjugated films (PCL-PAAC-CD34) resulted in a 4! - 9 fold (p<0.001) reduced platelet activation. PCL-PAAc however resulted in an increased contact activation on thromboelastography, and a poorer blood compatibility index (BCI) assay (43.4+/-2.3 vs 60.9+/-2.5%, p<0.05). PCL-PAAC-CD34 on the other hand resulted in delayed clot formation (r=19.3+/-1.5, k=6.8+/-0.6 min), reduced platelet adhesion and activation, and yielded the highest BCI score, indicating least thrombogenicity (69.3+/-3.2%). Our results suggest that CD34 antibody conjugation significantly improved the haemocompatibility of PAAc-conjugated muXPCL. PMID: 20214450 [PubMed - as supplied by publisher] | | |
| Tumor Engineering; the Other Face of Tissue Engineering.
March 11, 2010 at 7:12 AM
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| | Tumor Engineering; the Other Face of Tissue Engineering. Tissue Eng Part A. 2010 Mar 9; Authors: Bissell M, Ghajar CM Advances in Tissue Engineering have been accomplished for years by employing biomimetic strategies to provide cells with aspects of their original microenvironment necessary to reconstitute a unit of both form and function of a given tissue. We believe the most critical hallmark of cancer is loss of integration of architecture and function; thus, it stands to reason that similar strategies could be employed to understand tumor biology. In this commentary, we discuss work contributed by Fischbach-Teschl and colleagues to this special issue of Tissue Engineering in the context of so-called 'tumor engineering'; that is, the construction of complex cell culture models that recapitulate aspects of the in vivo tumor microenvironment to study the dynamics of tumor development, progression, and therapy on multiple scales. We provide examples of fundamental questions that could be answered by developing such models, and encourage the continued collaboration between physica! l scientists and life scientists not only for regenerative purposes, but also to unravel the complexity that is the tumor microenvironment. PMID: 20214448 [PubMed - as supplied by publisher] | | |
| Outcomes of total pelvic exenteration for colorectal cancer.
March 11, 2010 at 7:12 AM
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| | Outcomes of total pelvic exenteration for colorectal cancer. Hepatogastroenterology. 2009 Nov-Dec;56(96):1637-41 Authors: Nishio M, Sakakura C, Nagata T, Miyashita A, Hamada T, Ikoma H, Kubota T, Nakanishi M, Kimura A, Ichikawa D, Kikuchi S, Fujiwara H, Okamoto K, Ochiai T, Kokuba Y, Taniguchi H, Sonoyama T, Hagiwara A, Otsuji E BACKGROUND/AIMS: Pelvic recurrence occurs in 4-33% of patients who have undergone a curative resection of primary rectal cancer and is thus a serious problem. However, the best treatment for primary rectal cancer remains unclear. In the present study was assessed the outcomes of total pelvic exenteration for colorectal cancer retrospectively. METHODOLOGY: In the present study was investigated the medical charts of 25 patients who underwent total pelvic exenteration for primary colorectal cancer (n = 12) or postoperative local recurrence of colorectal cancer (n = 13) at the Department of Surgery (Division of Digestive Surgery) of the Kyoto Prefectural University of Medicine between the years 1997-2005. RESULTS: The mean disease-free time interval between the first operation for primary colorectal cancer and total pelvic exenteration for the recurrence was 919 days (range, 203-3460 days). Total pelvic exenteration required a mean operation time of 940 minutes (range! , 540-1395 minutes). The mean carcinoembryonic antigen (CEA) value was 25.5 ng/ml (range, 1-171.8 ng/ml). Five-year survival was achieved in 9 patients (36%) and inhospital death occurred in 3 patients (12%). The patients with curative resection survived significantly longer than the patients with non-curative resection. CONCLUSIONS: When curative resection is achieved, total pelvic exenteration for colorectal cancer can result in long-term survival. PMID: 20214208 [PubMed - in process] | | |
| Nanotechnology for bone materials.
March 11, 2010 at 7:12 AM
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| | Nanotechnology for bone materials. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009 May;1(3):336-51 Authors: Tran N, Webster TJ It has been established that for orthopedic-related research, nanomaterials (materials defined as those with constituent dimensions less than 100 nm in at least one direction) have superior properties compared to conventional counterparts. This review summarizes studies that have demonstrated enhanced in vitro and in vivo osteoblast (bone-forming cells) functions (such as adhesion, proliferation, synthesis of bone-related proteins, and deposition of calcium-containing mineral) on nanostructured metals, ceramics, polymers, and composites thereof compared to currently used implants. These results strongly imply that nanomaterials may improve osseointegration, which is crucial for long-term implant efficacy. This review also focuses on novel drug-carrying magnetic nanoparticles designed to treat various bone diseases (such as osteoporosis). Although further investigation of the in vivo responses and toxicity of these novel nanomaterials pertinent for orthopedic appli! cations are needed, nanotechnology clearly has already demonstrated the ability to produce better bone implants and therefore should be further investigated. PMID: 20049801 [PubMed - indexed for MEDLINE] | | |
| A novel flow-perfusion bioreactor supports 3D dynamic cell culture.
March 11, 2010 at 7:12 AM
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| | A novel flow-perfusion bioreactor supports 3D dynamic cell culture. J Biomed Biotechnol. 2009;2009:873816 Authors: Sailon AM, Allori AC, Davidson EH, Reformat DD, Allen RJ, Warren SM BACKGROUND: Bone engineering requires thicker three-dimensional constructs than the maximum thickness supported by standard cell-culture techniques (2 mm). A flow-perfusion bioreactor was developed to provide chemotransportation to thick (6 mm) scaffolds. METHODS: Polyurethane scaffolds, seeded with murine preosteoblasts, were loaded into a novel bioreactor. Control scaffolds remained in static culture. Samples were harvested at days 2, 4, 6, and 8 and analyzed for cellular distribution, viability, metabolic activity, and density at the periphery and core. RESULTS: By day 8, static scaffolds had a periphery cell density of 67% +/- 5.0%, while in the core it was 0.3% +/- 0.3%. Flow-perfused scaffolds demonstrated peripheral cell density of 94% +/- 8.3% and core density of 76% +/- 3.1% at day 8. CONCLUSIONS: Flow perfusion provides chemotransportation to thick scaffolds. This system may permit high throughput study of 3D tissues in vitro and enable prefabrication of! biological constructs large enough to solve clinical problems. PMID: 20037739 [PubMed - indexed for MEDLINE] | | |
| High harvest yield, high expansion, and phenotype stability of CD146 mesenchymal stromal cells from whole primitive human umbilical cord tissue.
March 11, 2010 at 7:12 AM
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| | High harvest yield, high expansion, and phenotype stability of CD146 mesenchymal stromal cells from whole primitive human umbilical cord tissue. J Biomed Biotechnol. 2009;2009:789526 Authors: Schugar RC, Chirieleison SM, Wescoe KE, Schmidt BT, Askew Y, Nance JJ, Evron JM, Peault B, Deasy BM Human umbilical cord blood is an excellent primitive source of noncontroversial stem cells for treatment of hematologic disorders; meanwhile, new stem cell candidates in the umbilical cord (UC) tissue could provide therapeutic cells for nonhematologic disorders. We show novel in situ characterization to identify and localize a panel of some markers expressed by mesenchymal stromal cells (MSCs; CD44, CD105, CD73, CD90) and CD146 in the UC. We describe enzymatic isolation and purification methods of different UC cell populations that do not require manual separation of the vessels and stroma of the coiled, helical-like UC tissue. Unique quantitation of in situ cell frequency and stromal cell counts upon harvest illustrate the potential to obtain high numerical yields with these methods. UC stromal cells can differentiate to the osteogenic and chondrogenic lineages and, under specific culturing conditions, they exhibit high expandability with unique long-term stabili! ty of their phenotype. The remarkable stability of the phenotype represents a novel finding for human MSCs, from any source, and supports the use of these cells as highly accessible stromal cells for both basic studies and potentially therapeutic applications such as allogeneic clinical use for musculoskeletal disorders. PMID: 20037738 [PubMed - indexed for MEDLINE] | | | | 
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