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| Polyester copolymer scaffolds enhance expression of bone markers in osteoblast-like cells.
March 6, 2010 at 6:26 AM
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| | Polyester copolymer scaffolds enhance expression of bone markers in osteoblast-like cells. J Biomed Mater Res A. 2010 Mar 4; Authors: Idris SB, Arvidson K, Plikk P, Ibrahim S, Finne-Wistrand A, Albertsson AC, Bolstad AI, Mustafa K In tissue engineering, the resorbable aliphatic polyester poly(L-lactide) (PLLA) is used as scaffolds in bone regeneration. Copolymers of poly(L-lactide)-co-(epsilon-caprolactone) [poly(LLA-co-CL)] and poly(L-lactide)-co-(1,5-dioxepan-2-one) [poly(LLA-co-DXO)], with superior mechanical properties to PLLA, have been developed to be used as scaffolds, but the influence on the osteogenic potential is unclear. This in vitro study of test scaffolds of poly(LLA-co-CL) and poly(LLA-co-DXO) using PLLA scaffolds as a control demonstrates the attachment and proliferation of human osteoblast-like cells (HOB) as measured by SEM and a methylthiazol tetrazolium (MTT) colorimetric assay, and the progression of HOB osteogenesis for up to 3 weeks; expressed as synthesis of the osteoblast differentiation markers: collagen type 1 (Col 1), alkaline phosphatase, bone sialoprotein, osteocalcin (OC), osteopontin and runt related gene 2 (Runx2). Surface analysis disclosed excellent surfa! ce attachment, spread and penetration of the cells into the pores of the test scaffolds compared to the PLLA. MTT results indicated that test scaffolds enhanced the proliferation of HOBs. Cells grown on the test scaffolds demonstrated higher synthesis of Col 1 and OC and also increased bone markers mRNA expression. Compared to scaffolds of PLLA, the poly(LLA-co-CL) and poly(LLA-co-DXO) scaffolds enhanced attachment, proliferation, and expression of osteogenic markers by HOBs in vitro. Therefore, these scaffolds might be appropriate carriers for bone engineering. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20205238 [PubMed - as supplied by publisher] | | |
| Alternating current electric field effects on neural stem cell viability and differentiation.
March 6, 2010 at 6:26 AM
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| | Alternating current electric field effects on neural stem cell viability and differentiation. Biotechnol Prog. 2010 Jan 29; Authors: Matos MA, Cicerone MT Methods utilizing stem cells hold tremendous promise for tissue engineering applications; however, many issues must be worked out before these therapies can be routinely applied. Utilization of external cues for preimplantation expansion and differentiation offers a potentially viable approach to the use of stem cells in tissue engineering. The studies reported here focus on the response of murine neural stem cells encapsulated in alginate hydrogel beads to alternating current electric fields. Cell viability and differentiation was studied as a function of electric field magnitude and frequency. We applied fields of frequency (0.1-10) Hz, and found a marked peak in neural stem cell viability under oscillatory electric fields with a frequency of 1 Hz. We also found an enhanced propensity for astrocyte differentiation over neuronal differentiation in the 1 Hz cultures, as compared to the other field frequencies we studied. Published 2010 American Institute of Chemic! al Engineers Biotechnol. Prog., 2010. PMID: 20205161 [PubMed - as supplied by publisher] | | |
| Poly(ethylene glycol)-grafted poly(propylene fumarate) networks and parabolic dependence of MC3T3 cell behavior on the network composition.
March 6, 2010 at 6:26 AM
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| | Poly(ethylene glycol)-grafted poly(propylene fumarate) networks and parabolic dependence of MC3T3 cell behavior on the network composition. Biomaterials. 2010 Mar 2; Authors: Cai L, Wang K, Wang S We present a method to modify poly(propylene fumarate) (PPF), an injectable biomaterial for bone-tissue-engineering applications, by photo-crosslinking it with methoxy poly(ethylene glycol) monoacrylate (mPEGA) at various mPEGA compositions of 0-30%. The bulk properties such as thermal and rheological properties of uncrosslinked mPEGA/PPF blends and the mechanical properties of photo-crosslinked mPEGA/PPF blends were also investigated and correlated with surface characteristics to elaborate on the modulation of mouse MC3T3 cell adhesion, spreading, proliferation and differentiation through controlled physicochemical properties. Unlike PPF crosslinked with PEG dimethacrylate, mPEGA chains tethered on the surface of crosslinked PPF did not influence the swelling ratio in water while increased surface hydrophilicity greatly. Meanwhile, surface frictional coefficient and the capability of adsorbing proteins from cell culture medium decreased continuously with increasi! ng the mPEGA composition in mPEGA/PPF networks. Demonstrating cell repulsive effect at the mPEGA compositions higher than 7%, the modified surfaces improved MC3T3 cell attachment, proliferation and differentiation, which reached maxima at the mPEGA composition of 5-7%. Besides revealing that mPEGA pendant chains could enhance cell responses by increasing hydrophilicity when their fraction on the hydrophobic surface was small, the present study also offered a new method of improving the wettability and performance of the scaffolds made from PPF for bone repair. PMID: 20202682 [PubMed - as supplied by publisher] | | |
| Direct differentiation of human embryonic stem cells into selective neurons on nanoscale ridge/groove pattern arrays.
March 6, 2010 at 6:26 AM
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| | Direct differentiation of human embryonic stem cells into selective neurons on nanoscale ridge/groove pattern arrays. Biomaterials. 2010 Mar 2; Authors: Lee MR, Kwon KW, Jung H, Kim HN, Suh KY, Kim K, Kim KS Human embryonic stem cells (hESCs) are pluripotent cells that have the potential to be used for tissue engineering and regenerative medicine. Repairing nerve injury by differentiating hESCs into a neuronal lineage is one important application of hESCs. Biochemical and biological agents are widely used to induce hESC differentiation. However, it would be better if we could induce differentiation of hESCs without such agents because these factors are expensive and it is difficult to control the optimal concentrations for efficient differentiation with reduced side effects. Moreover, the mechanism of differentiation induced by these factors is still not fully understood. In this study, we present evidence that nanoscale ridge/groove pattern arrays alone can effectively and rapidly induce the differentiation of hESCs into a neuronal lineage without the use any differentiation-inducing agents. Using UV-assisted capillary force lithography, we constructed nanoscale ridg! e/groove pattern arrays with a dimension and alignment that were finely controlled over a large area. Human embryonic stem cells seeded onto the 350-nm ridge/groove pattern arrays differentiated into neuronal lineage after five days, in the absence differentiation-inducing agents. This nanoscale technique could be used for a new neuronal differentiation protocol of hESCs and may also be useful for nanostructured scaffolding for nerve injury repair. PMID: 20202681 [PubMed - as supplied by publisher] | | |
| Manual limbal markings versus iris-registration software for correction of myopic astigmatism by laser in situ keratomileusis.
March 6, 2010 at 6:26 AM
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| | Manual limbal markings versus iris-registration software for correction of myopic astigmatism by laser in situ keratomileusis. J Cataract Refract Surg. 2010 Mar;36(3):431-436 Authors: Shen EP, Chen WL, Hu FR PURPOSE: To compare the efficacy and safety of manual limbal markings and wavefront-guided treatment with iris-registration software in laser in situ keratomileusis (LASIK) for myopic astigmatism. SETTING: National Taiwan University Hospital, Taipei, Taiwan. METHODS: Eyes with myopic astigmatism had LASIK with a Technolas 217z laser. Eyes in the limbal-marking group had conventional LASIK (PlanoScan or Zyoptix tissue-saving algorithm) with manual cyclotorsional-error adjustments according to 2 limbal marks. Eyes in the iris-registration group had wavefront-guided ablation (Zyoptix) in which cyclotorsional errors were automatically detected and adjusted. Refraction, corneal topography, and visual acuity data were compared between groups. Vector analysis was by the Alpins method. RESULTS: The mean preoperative spherical equivalent (SE) was -6.64 diopters (D) +/- 1.99 (SD) in the limbal-marking group and -6.72 +/- 1.86 D in the iris-registration group (P = .92). At 6! months, the mean SE was -0.42 +/- 0.63 D and -0.47 +/- 0.62 D, respectively (P = .08). There was no statistically significant difference between groups in the astigmatism correction, success, or flattening index values using 6-month postoperative refractive data. The angle of error was within +/-10 degrees in 73% of eyes in the limbal-marking group and 75% of eyes in the iris-registration group. CONCLUSION: Manual limbal markings and iris-registration software were equally effective and safe in LASIK for myopic astigmatism, showing that checking cyclotorsion by manual limbal markings is a safe alternative when automated systems are not available. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. PMID: 20202541 [PubMed - as supplied by publisher] | | |
| The chemical defensive system in the pathobiology of idiopathic environment-associated diseases.
March 6, 2010 at 6:26 AM
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| | The chemical defensive system in the pathobiology of idiopathic environment-associated diseases. Curr Drug Metab. 2009 Oct 1;10(8):914-31 Authors: Korkina L, Scordo G, Deeva I, Cesareo E, De Luca C Chemical defensive system consisting of bio-sensoring, transmitting, and responsive elements has been evolved to protect multi-cellular organisms against environmental chemical insults (xenobiotics) and to maintain homeostasis of endogenous low molecular weight metabolites (endobiotics). Both genetic and epigenetic defects of the system in association with carcinogenesis and individual sensitivity to anti-tumor therapies have been intensely studied. Recently, several non-tumor human pathologies with evident environmental components such as rather rare functional syndromes (multiple chemical sensitivity, chronic fatigue, Persian Gulf, and fibromyalgia now collectively labeled as idiopathic environmental intolerances) and common diseases (vitiligo and systemic lupus erythematosus) have become subjects of the research on the impaired metabolism and detoxification of xenobiotics and endogenous toxins. Here, we collected and critically reviewed epidemiological, genetic! , and biochemical data on the involvement and possible role of cytochrome P450 super family enzymes, glutathione-S-transferase isozymes, catechol-O-methyl-transferase, UDP-glucuronosyl transferases, and proteins detoxifying inorganic and organic peroxides (catalase, glutathione peroxidase, and peroxiredoxin) in the above pathologies. Genetic predisposition assessed mainly by single nucleotide polymorphism and gene expression analyses revealed correlations between defects in genes encoding xenobiotic-metabolizing and/or detoxifying enzymes and risk/severity of these syndromes/diseases. Proteome analysis identified abnormal expression of the enzymes. Their functions were affected epigenetically leading to metabolic impairment and, as a consequence, to the negative health outcomes shared by some of these pathologies. Data obtained so far suggest that distinct components of the chemical defensive system could be suitable molecular targets for future pathogenic therapies. PMID: 20201826 [PubMed - in process] | | |
| Biomaterials and mesenchymal stem cells for regenerative medicine.
March 6, 2010 at 6:26 AM
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| | Biomaterials and mesenchymal stem cells for regenerative medicine. Recent Pat Biotechnol. 2010 Jan 1;4(1):1-22 Authors: Zippel N, Schulze M, Tobiasch E The reconstruction of hard and soft tissues is a major challenge in regenerative medicine, since diseases or traumas are causing increasing numbers of tissue defects due to the aging of the population. Modern tissue engineering is increasingly using three-dimensional structured biomaterials in combination with stem cells as cell source, since mature cells are often not available in sufficient amounts or quality. Biomaterial scaffolds are developed that not only serve as cell carriers providing mechanical support, but actively influence cellular responses including cell attachment and proliferation. Chemical modifications such as the incorporation of chemotactic factors or cell adhesion molecules are examined for their ability to enhance tissue development successfully. E.g. growth factors have been investigated extensively as substances able to support cell growth, differentiation and angiogenesis. Thus, continuously new patents and studies are published, which ar! e investigating the advantages and disadvantages of different biomaterials or cell types for the regeneration of specific tissues. This review focuses on biomaterials, including natural and synthetic polymers, ceramics and corresponding composites used as scaffold materials to support cell proliferation and differentiation for hard and soft tissues regeneration. In addition, the local delivery of drugs by scaffold biomaterials is discussed. PMID: 20201799 [PubMed - in process] | | |
| Molecular Architecture of Electroactive and Biodegradable Copolymers Composed of Polylactide and Carboxyl-Capped Aniline Trimer.
March 6, 2010 at 6:26 AM
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| | Molecular Architecture of Electroactive and Biodegradable Copolymers Composed of Polylactide and Carboxyl-Capped Aniline Trimer. Biomacromolecules. 2010 Mar 4; Authors: Guo B, Finne-Wistrand A, Albertsson AC Two-, four-, and six-armed branched copolymers with electroactive and biodegradable properties were synthesized by coupling reactions between poly(l-lactides) (PLLAs) with different architecture and carboxyl-capped aniline trimer (CCAT). The aniline oligomer CCAT was prepared from amino-capped aniline trimer and succinic anhydride. FT-IR, NMR, and SEC analyses confirmed the structure of the branched copolymers. UV-vis spectra and cyclic voltammetry of CCAT and copolymer solution showed good electroactive properties, similar to those of polyaniline. The water contact angle of the PLLAs was the highest, followed by the undoped copolymer and the doped copolymers. The values of doped four-armed copolymers were 54-63 degrees . Thermal properties of the polymers were studied by DSC and TGA. The copolymers had better thermal stability than the pure PLLAs, and the T(g) between 48-58 degrees C and T(m) between 146-177 degrees C of the copolymers were lower than those of th! e pure PLLA counterparts. This kind of electroactive and biodegradable copolymer has a great potential for applications in cardiovascular or neuronal tissue engineering. PMID: 20201489 [PubMed - as supplied by publisher] | | |
| Nucleic acid delivery to magnetically-labeled cells in a 2D array and at the luminal surface of cell culture tube and their detection by MRI.
March 6, 2010 at 6:26 AM
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| | Nucleic acid delivery to magnetically-labeled cells in a 2D array and at the luminal surface of cell culture tube and their detection by MRI. J Biomed Nanotechnol. 2009 Dec;5(6):692-706 Authors: Mykhaylyk O, Steingötter A, Perea H, Aigner J, Botnar R, Plank C The magnetic labeling of living cells has become of major interest in the areas of cell therapy and tissue engineering. Magnetically labeled cells have been reported to allow increased and controlled seeding, tracking, and targeting of cells. In this work, we comprehensively characterize magnetic nanoparticles (MNPs) possessing a magnetite core of about 11 nm, and which are coated with the fluorinated surfactant F(CF2)nCH2CH2SCH2CH2C(O)OLi and 1,9-nonandithiol (NDT) for the nonspecific labeling of human pulmonary epithelial (H441) cells. We achieved a non-specific cell loading of 38 pg Fe/cell. In this work we combine magnetic cell labeling with subsequent genetic modification of the cells with non-viral transfection complexes associated with PEI-Mag2 magnetic nanoparticles upon gradient magnetic field application called magnetofection. The magnetic responsiveness and magnetic moment of the MNP-labeled cells and the magnetic transfection complexes were evaluated b! y measuring changes in the turbidity of prepared cells suspensions and complexes in a defined magnetic gradient field. The magnetic responsiveness of cells that were loaded with NDT-Mag1 MNPs (20-38 pg Fe/cell) was sufficient to engraft these labeled cells magnetically onto the luminal surface of a culture tube. This was achieved using a solenoid electromagnet that produced a radial magnetic field of 20-30 mT at the seeding area and an axial gradient field of approx. 4 T/m. The MNP-labeled cells were magnetofected in 2D arrays (well plates) and at the luminal surface of cell culture tube. The optimized magnetic pre-labeling of cells did not interfere with, or even increased, the efficiency of magnetofection in both culture systems without causing cell toxicity. Cell loading of 38 pg Fe/cell of NDT-Mag1 MNPs resulted in high transverse relaxivities r2*, thus allowing the MRI detection of cell concentrations that were equivalent to (or higher than) 1.2 microg Fe/ml. Multi-ech! o gradient echo imaging and R2* mapping detected as few as 153! 3 MNP-la beled H441 cells localized within a 50 microl fibrin clot and MNP-labeled cell monolayers that were engrafted on the luminal surface of a cell culture tube. Further loading of cells with MNPs did not increase either the magnetic responsiveness of the cells or the sensitivity of MR imaging. In summary, the NDT-Mag1 magnetic nanoparticles provided a high cell-loading efficiency, resulting in strong cell magnetic moments and a high sensitivity to MRI detection. The transfection ability of the labeled cells was also maintained, thereby increasing the magnetofection efficiency. PMID: 20201231 [PubMed - in process] | | |
| Recent progress in polyphosphoesters: from controlled synthesis to biomedical applications.
March 6, 2010 at 6:26 AM
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| | Recent progress in polyphosphoesters: from controlled synthesis to biomedical applications. Macromol Biosci. 2009 Dec 8;9(12):1154-64 Authors: Wang YC, Yuan YY, Du JZ, Yang XZ, Wang J Polyphosphoesters (PPEs) with repeating phosphoester bonds in the backbone are structurally versatile, biocompatible, and biodegradable through hydrolysis as well as enzymatic digestion under physiological conditions. They are appealing for biological applications because of their potential functionality, biocompatibility, and similarity to biomacromolecules such as nucleic acids. The expanding scope of PPEs in materials science, especially as biomaterials, is described in this review. We mainly focus on controlled synthetic methods of PPEs, which provide access to novel and complex polymer structures, especially for block copolymers. The hydrolytic and enzymatic degradation of PPEs, thermoresponsive PPEs, and biomedical applications have also been discussed. PMID: 19924681 [PubMed - indexed for MEDLINE] | | |
| Electrospun scaffolds for stem cell engineering.
March 6, 2010 at 6:26 AM
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| | Electrospun scaffolds for stem cell engineering. Adv Drug Deliv Rev. 2009 Oct 5;61(12):1084-96 Authors: Lim SH, Mao HQ Stem cells interact with and respond to a myriad of signals emanating from their extracellular microenvironment. The ability to harness the regenerative potential of stem cells via a synthetic matrix has promising implications for regenerative medicine. Electrospun fibrous scaffolds can be prepared with high degree of control over their structure creating highly porous meshes of ultrafine fibers that resemble the extracellular matrix topography, and are amenable to various functional modifications targeted towards enhancing stem cell survival and proliferation, directing specific stem cell fates, or promoting tissue organization. The feasibility of using such a scaffold platform to present integrated topographical and biochemical signals that are essential to stem cell manipulation has been demonstrated. Future application of this versatile scaffold platform to human embryonic and induced pluripotent stem cells for functional tissue repair and regeneration will fu! rther expand its potential for regenerative therapies. PMID: 19647024 [PubMed - indexed for MEDLINE] | | |
| Nanotechnology and its applications in surgery.
March 6, 2010 at 6:06 AM
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| | Nanotechnology and its applications in surgery. Br J Surg. 2010 Mar 4;97(4):463-465 Authors: Loizidou M, Seifalian AM PMID: 20205212 [PubMed - as supplied by publisher] | | |
| Isolation and culture of adult mouse hepatocytes.
March 6, 2010 at 6:06 AM
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| | Isolation and culture of adult mouse hepatocytes. Methods Mol Biol. 2010;633:185-96 Authors: Li WC, Ralphs KL, Tosh D The liver performs a multitude of functions including the regulation of carbohydrate, fat, and protein metabolism, the detoxification of endo- and xenobiotics, and the synthesis and secretion of plasma proteins and bile. Isolated hepatocytes constitute a useful technique for studying liver function in an in vitro setting. Here we describe a method for the isolation of hepatocytes from adult mouse liver. The principle of the method is the two-step collagenase perfusion technique which involves sequential perfusion of the liver with ethylenediaminetetraacetic acid and collagenase. Following isolation, the cells can either be used for short-term studies or, alternatively, maintained in culture for prolonged periods to study long-term changes in gene expression. The protocol for mouse hepatocyte isolation may be applied to both normal and transgenic mice. PMID: 20204628 [PubMed - in process] | | |
| Isolation and culture of embryonic pancreas and liver.
March 6, 2010 at 6:06 AM
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| | Isolation and culture of embryonic pancreas and liver. Methods Mol Biol. 2010;633:91-9 Authors: Burke ZD, Li WC, Slack JM, Tosh D Culturing embryonic tissue in an in vitro setting offers the unique ability to manipulate the external medium and therefore to investigate the pathways involved in regulating normal organogenesis as well as providing models for developmental disorders. Here we describe a system for the in vitro culture of the dorsal pancreatic buds and liver buds from mouse embryos. The tissues are dissected from day 9.0 or 11.5 mouse embryos. The tissues are placed on fibronectin-coated coverslips in serum-containing medium and allowed to attach. Over the next few days, the buds grow as flattened structures which are thin enough to allow the use of wholemount immunostaining methods. PMID: 20204622 [PubMed - in process] | | |
| Isolation, culture, and characterisation of mouse embryonic oesophagus and intestine.
March 6, 2010 at 6:06 AM
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| | Isolation, culture, and characterisation of mouse embryonic oesophagus and intestine. Methods Mol Biol. 2010;633:81-90 Authors: Quinlan JM, Yu WY, Tosh D The gastrointestinal tract of vertebrates is lined by epithelium that develops from the endodermal germ layer. The oesophagus and intestine form part of the gastrointestinal tract and studying the normal development of both tissues is difficult due to lack of suitable in vitro model systems. One of the criteria for a reliable culture model includes the ability to carry out real-time observations in vitro. The method we describe here is based on the isolation of embryonic oesophagus and intestine from 11.5-day-old embryos and culture on fibronectin-coated coverslips in basal Eagle's medium and 20% fetal bovine serum. This model permits real-time observations of both tissues and over a few days in culture, markers of differentiation appear. This culture system appears to recapitulate normal oesophagus and intestine development. PMID: 20204621 [PubMed - in process] | | |
| How to improve the success rate of mouse cloning technology.
March 6, 2010 at 6:06 AM
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| | How to improve the success rate of mouse cloning technology. J Reprod Dev. 2010 Jan;56(1):20-30 Authors: Thuan NV, Kishigami S, Wakayama T It has now been 13 years since the first cloned mammal Dolly the sheep was generated from somatic cells using nuclear transfer (SCNT). Since then, this technique has been considered an important tool not only for animal reproduction but also for regenerative medicine. However, the success rate is still very low and the mechanisms involved in genomic reprogramming are not yet clear. Moreover, the NT technique requires donated fresh oocyte, which raises ethical problems for production of human cloned embryo. For this reason, the use of induced pluripotent stem cells for genomic reprogramming and for regenerative medicine is currently a hot topic in this field. However, we believe that the NT approach remains the only valid way for the study of reproduction and basic biology. For example, only the NT approach can reveal dynamic and global modifications in the epigenome without using genetic modification, and it can generate offspring from a single cell or even a froz! en dead body. Thanks to much hard work by many groups, cloning success rates are increasing slightly year by year, and NT cloning is now becoming a more applicable method. This review describes how to improve the efficiency of cloning, the establishment of clone-derived embryonic stem cells and further applications. PMID: 20203432 [PubMed - in process] | | |
| Direct differentiation of human embryonic stem cells into selective neurons on nanoscale ridge/groove pattern arrays.
March 6, 2010 at 6:06 AM
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| | Direct differentiation of human embryonic stem cells into selective neurons on nanoscale ridge/groove pattern arrays. Biomaterials. 2010 Mar 2; Authors: Lee MR, Kwon KW, Jung H, Kim HN, Suh KY, Kim K, Kim KS Human embryonic stem cells (hESCs) are pluripotent cells that have the potential to be used for tissue engineering and regenerative medicine. Repairing nerve injury by differentiating hESCs into a neuronal lineage is one important application of hESCs. Biochemical and biological agents are widely used to induce hESC differentiation. However, it would be better if we could induce differentiation of hESCs without such agents because these factors are expensive and it is difficult to control the optimal concentrations for efficient differentiation with reduced side effects. Moreover, the mechanism of differentiation induced by these factors is still not fully understood. In this study, we present evidence that nanoscale ridge/groove pattern arrays alone can effectively and rapidly induce the differentiation of hESCs into a neuronal lineage without the use any differentiation-inducing agents. Using UV-assisted capillary force lithography, we constructed nanoscale ridg! e/groove pattern arrays with a dimension and alignment that were finely controlled over a large area. Human embryonic stem cells seeded onto the 350-nm ridge/groove pattern arrays differentiated into neuronal lineage after five days, in the absence differentiation-inducing agents. This nanoscale technique could be used for a new neuronal differentiation protocol of hESCs and may also be useful for nanostructured scaffolding for nerve injury repair. PMID: 20202681 [PubMed - as supplied by publisher] | | |
| Notch and cardiac outflow tract development.
March 6, 2010 at 6:06 AM
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| | Notch and cardiac outflow tract development. Ann N Y Acad Sci. 2010 Feb;1188:184-90 Authors: Jain R, Rentschler S, Epstein JA Congenital heart disease represents the most common form of human birth defect, occurring in nearly 1 in 100 live births. An increasing number of patients with these defects are surviving infancy. Approximately one-third of congenital heart defects involve malformations of the outflow tract. Related defects are found in isolation and as part of common human syndromes. Our laboratory has investigated mechanisms of cardiac morphogenesis with particular attention to outflow tract formation. During cardiogenesis, neural crest cells interact with second heart field myocardium and endocardial cushion mesenchyme. Our recent work demonstrates that Jagged1/Notch signaling within the second heart field initiates a signaling cascade involving Fgf8, Bmp4, and downstream effectors that modulate outflow tract development and aortic arch artery patterning. Hence, complex tissue-tissue interactions and integration of multiple pathways converge to orchestrate proper patterning of ! the outflow region. The role of Notch signaling in adult cardiac homeostasis and disease is an area of active investigation. PMID: 20201902 [PubMed - in process] | | |
| Vascularization shaping the heart.
March 6, 2010 at 6:06 AM
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| | Vascularization shaping the heart. Ann N Y Acad Sci. 2010 Feb;1188:46-51 Authors: Lesman A, Gepstein L, Levenberg S Myocardial infarction can lead to irreversible heart failure. In an attempt to restore function in the failing heart, tissue-engineered cardiac constructs can be applied to repopulate scar tissue with a new pool of contractile cells. Effective engineering of viable thick complex tissue-constructs requires intense vascularization. Furthermore, endothelial-cardiomyocyte crosstalk plays a key role in mutually enhancing tissue functionality, which can further improve construct survival. The ability to generate an engineered, vascularized muscle tissue was demonstrated by us using the skeletal and the cardiac muscle models. In the skeletal model, we showed that prevascularization of the construct promoted perfusion of the graft. More recently, we successfully generated a beating human cardiac muscle-construct, containing an endothelial network, by co-culturing human embryonic stem cell-derived-cardiomyocytes, fibroblasts, and endothelial cells within biodegradable scaf! folds. Such muscle-constructs could contribute significantly to the emerging discipline of cardiovascular regenerative medicine as well as to the study of the important role of tissue vascularization. PMID: 20201885 [PubMed - in process] | | |
| Cell and gene therapy strategies for the treatment of postmyocardial infarction ventricular arrhythmias.
March 6, 2010 at 6:06 AM
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| | Cell and gene therapy strategies for the treatment of postmyocardial infarction ventricular arrhythmias. Ann N Y Acad Sci. 2010 Feb;1188:32-8 Authors: Gepstein L Ventricular arrhythmias in the setting of a healed myocardial infarction represent a major cause of morbidity and mortality. The underlying mechanism is the presence of slow conduction tissue within the infarct border zone. In the current review we describe experimental gene and cell therapy approaches targeting the electrophysiologic substrate of the border zone, with the aim of preventing postinfarction ventricular arrhythmias. These include strategies that aim to prevent reentry by improving conduction velocity or by prolonging refractoriness. Attempts to augment conduction velocity include cardiomyocyte transplantation to regenerate the infarct, overexpression of unique sodium channels (to improve excitability), and methods to improve cell-to-cell coupling. Strategies to prolong refractoriness include gene therapy to prolong action potential duration or cell therapy using engineered cell grafts transfected ex vivo to express unique potassium channels. Finally,! we will also discuss the potential advantages and drawbacks of these strategies as well as a road map for future clinical use. PMID: 20201883 [PubMed - in process] | | | | 
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