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| Low Connexin Channel-Dependent Intercellular Communication in Human Adult Hematopoietic Progenitor/Stem Cells: Probing Mechanisms of Autologous Stem Cell Therapy.
March 20, 2010 at 7:35 AM
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| | Low Connexin Channel-Dependent Intercellular Communication in Human Adult Hematopoietic Progenitor/Stem Cells: Probing Mechanisms of Autologous Stem Cell Therapy. Cell Commun Adhes. 2010 Mar 19; Authors: Yang J, Darley RL, Hallett M, Howard Evans W Abstract Human bone marrow is a clinical source of autologous progenitor stem cells showing promise for cardiac repair following ischemic insult. Functional improvements following delivery of adult bone marrow CD34(+) cells into heart tissue may require metabolic/electrical communication between participating cells. Since connexin43 (Cx43) channels are implicated in cardiogenesis and provide intercellular connectivity in the heart, the authors analyzed the expression of 20 connexins (Cx) in CD34(+) cells and in monocytes and granulocytes in bone marrow and spinal cord. Reverse transcriptase-polymerase chain reaction (RT-PCR) detected only low expression of Cx43 and Cx37. Very low level dye coupling was detected by flow cytometry between CD34(+) cells and other Cx43 expressing cells, including HL-1 cardiac cells, and was not inhibited by specific gap junction inhibitors. The results indicate that CD34(+) cells are unlikely to communicate via gap junctions and the a! uthors conclude that use of CD34(+) cells to repair damaged hearts is unlikely to involve gap junctions. The results concur with the hypothesis that bone marrow cells elicit improved cardiac function through release of undefined paracrine mediators. PMID: 20298144 [PubMed - as supplied by publisher] | | |
| Microenvironment modulates osteogenic cell lineage commitment in differentiated embryonic stem cells.
March 20, 2010 at 6:55 AM
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| | Microenvironment modulates osteogenic cell lineage commitment in differentiated embryonic stem cells. PLoS One. 2010;5(3):e9663 Authors: Yamashita A, Nishikawa S, Rancourt DE BACKGROUND: Due to their self-renewal, embryonic stem cells (ESCs) are attractive cells for applications in regenerative medicine and tissue engineering. Although ESC differentiation has been used as a platform for generating bone in vitro and in vivo, the results have been unsatisfactory at best. It is possible that the traditional culture methods, which have been used, are not optimal and that other approaches must be explored. METHODOLOGY/PRINCIPAL FINDINGS: ESCs were differentiated into osteoblast lineage using a micro-mass approach. In response to osteogenic differentiation medium, many cells underwent apoptosis, while others left the micro-mass, forming small aggregates in suspension. These aggregates were cultured in three different culture conditions (adhesion, static suspension, and stirred suspension), then examined for osteogenic potential in vitro and in vivo. In adhesion culture, ESCs primed to become osteoblasts recommitted to the adipocyte lineage i! n vitro. In a static suspension culture, resulting porous aggregates expressed osteoblasts markers and formed bone in vivo via intermembranous ossification. In a stirred suspension culture, resulting non-porous aggregates suppressed osteoblast differentiation in favor of expanding progenitor cells. CONCLUSIONS/SIGNIFICANCE: We demonstrate that microenvironment modulates cell fate and subsequent tissue formation during ESC differentiation. For effective tissue engineering using ESCs, it is important to develop optimized cell culture/differentiation conditions based upon the influence of microenvironment. PMID: 20300192 [PubMed - in process] | | |
| UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis.
March 20, 2010 at 6:55 AM
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| | UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis. EMBO J. 2010 Mar 18; Authors: Seenundun S, Rampalli S, Liu QC, Aziz A, Palii C, Hong S, Blais A, Brand M, Ge K, Dilworth FJ Polycomb (PcG) and Trithorax (TrxG) group proteins act antagonistically to establish tissue-specific patterns of gene expression. The PcG protein Ezh2 facilitates repression by catalysing histone H3-Lys27 trimethylation (H3K27me3). For expression, H3K27me3 marks are removed and replaced by TrxG protein catalysed histone H3-Lys4 trimethylation (H3K4me3). Although H3K27 demethylases have been identified, the mechanism by which these enzymes are targeted to specific genomic regions to remove H3K27me3 marks has not been established. Here, we demonstrate a two-step mechanism for UTX-mediated demethylation at muscle-specific genes during myogenesis. Although the transactivator Six4 initially recruits UTX to the regulatory region of muscle genes, the resulting loss of H3K27me3 marks is limited to the region upstream of the transcriptional start site. Removal of the repressive H3K27me3 mark within the coding region then requires RNA Polymerase II (Pol II) elongation. Inte! restingly, blocking Pol II elongation on transcribed genes leads to increased H3K27me3 within the coding region, and formation of bivalent (H3K27me3/H3K4me3) chromatin domains. Thus, removal of repressive H3K27me3 marks by UTX occurs through targeted recruitment followed by spreading across the gene. PMID: 20300060 [PubMed - as supplied by publisher] | | |
| Magnetic carbon nanotube labelling for haematopoietic stem/progenitor cell tracking.
March 20, 2010 at 6:55 AM
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| | Magnetic carbon nanotube labelling for haematopoietic stem/progenitor cell tracking. Nanotechnology. 2010 Mar 19;21(15):155101 Authors: Gul H, Lu W, Xu P, Xing J, Chen J Haematopoietic stem and progenitor cell (HSPC) research has significantly contributed to the understanding and harnessing of haematopoiesis for regenerative medicine. However, the methodology for real-time tracking HSPC in vivo is still lacking, which seriously restricts the progress of research. Recently, magnetic carbon nanotubes (mCNT) have generated great excitement because they have been successfully used as vehicles to deliver a lot of biomolecules into various cells. There is, however, no report about mCNT being used for tracking HSPC. In this paper, we investigated the uptake efficiency of fluorescein-isothiocyanate-labelled mCNT (FITC-mCNT) into HSPC and their effect on the cytotoxicity and differentiation of HSPC. We found that cellular uptake of FITC-mCNT was concentration-and time-dependent. The uptake of FITC-mCNT into HSPC reached up to 100% with the highest mean fluorescence (MF). More importantly, efficient FITC-mCNT uptake has no adverse effect on! the cell viability, cytotoxicity and differentiation of HSPC as confirmed by colony-forming unit assay (CFU). In conclusion, the results reported here suggest the further tailoring of mCNT for their use in HSPC labelling/tracking in vivo or gene delivery into HSPC. PMID: 20299726 [PubMed - as supplied by publisher] | | |
| Development of evaluation system for bioactive substances using human artificial chromosome-mediated osteocalcin gene expression.
March 20, 2010 at 6:55 AM
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| | Development of evaluation system for bioactive substances using human artificial chromosome-mediated osteocalcin gene expression. J Biochem. 2010 Mar 17; Authors: Takahashi Y, Tsuji S, Kazuki Y, Noguchi M, Arifuku I, Umebayashi Y, Nakanishi T, Oshimura M, Sato K Bioactive substances in daily food and supplements are expected to prevent various lifestyle-related diseases. Recently, many evaluation systems for bioactive substances were developed with cell lines integrated with green fluorescence protein (GFP) reporter gene. To evaluate osteogensis activity in functional food, we developed a novel cell line that reports osteocalcin gene expression using the human artificial chromosome (HAC) vector. HAC vectors are able to avoid various problems in usual plasmid vector such as difficulty in control of transgene copy number. HAC is transmitted to cells as an independent chromosome from host chromosomes, and expresses transgenes depending on host cell circumstances. We established chinese hamster ovary cell lines that carried GFP gene regulated by osteocalcin gene promoter on the HAC. Expression of GFP was responded to vitamin D(3) (1alpha,25(OH)(2)D(3)). Furthermore, we constructed HAC vector bearing tandem repeats of reporter! gene unit, to enhance intensity of gene expression. GFP expression in these reporter cells is related to the copy number of reporter gene units. Using the evaluation system for bioactive substances, we could show osteogenic activity in some fish oils. PMID: 20299329 [PubMed - as supplied by publisher] | | |
| Psychometric Validation of the Manual Ability Measure-36 (MAM-36) in Patients With Neurologic and Musculoskeletal Disorders.
March 20, 2010 at 6:55 AM
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| | Psychometric Validation of the Manual Ability Measure-36 (MAM-36) in Patients With Neurologic and Musculoskeletal Disorders. Arch Phys Med Rehabil. 2010 Mar;91(3):414-420 Authors: Chen CC, Bode RK Chen CC, Bode RK. Psychometric validation of the Manual Ability Measure-36 (MAM-36) in patients with neurologic and musculoskeletal disorders. OBJECTIVES: To evaluate the psychometric properties of the Manual Ability Measure-36 (MAM-36), a new hand function outcome measure, and to examine differences in manual abilities and item parameters in patients with neurologic and musculoskeletal conditions. DESIGN: Convenience sample from 2 time periods, cross-sectional. SETTING: Outpatient rehabilitation units and private hand clinics. PARTICIPANTS: Patients (N=337; mean age, 50.3+/-14.9y) with a variety of neurologic and musculoskeletal (orthopedic) diagnoses. Most of these individuals were community dwelling, and all had residual functional limitations in the hand(s). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rasch analysis was performed on MAM-36 data to evaluate both scale structure and psychometric properties, which include rating distribution, step measu! res, item fit, separation, and dimensionality. A t test was performed to examine the differences in manual abilities in patients with the 2 conditions. Uniform differential item functioning (DIF) between neurologic and musculoskeletal groups was examined. (DIF occurs when subgroup members within the sample with the same level of the underlying trait being measured respond differently to an individual item.) Manual ability estimates were recalibrated with step and common item anchoring; they were compared with those derived from the original analysis. RESULTS: The 36 items measured a single construct with no misfitting items. The scale was used as intended. The items can reliably separate the participants into 5 ability strata. Neurologic patients had a significantly lower mean manual ability than musculoskeletal patients. Fourteen items exhibited DIF. However, DIF had no effect on either scale quality or calibration of manual ability. We decided that a single rating scale i! s appropriate for both groups. CONCLUSIONS: This study showed ! that the MAM-36 has more than adequate psychometric properties and can be used as a generic outcome measure for patients with a wide variety of clinical diagnoses. PMID: 20298833 [PubMed - as supplied by publisher] | | |
| The role of Cdx2 in Barrett's metaplasia.
March 20, 2010 at 6:55 AM
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| | The role of Cdx2 in Barrett's metaplasia. Biochem Soc Trans. 2010 Apr 1;38(2):364-9 Authors: Colleypriest BJ, Farrant JM, Slack JM, Tosh D Metaplasia (or transdifferentiation) is defined as the transformation of one tissue type to another. Clues to the molecular mechanisms that control the development of metaplasia are implied from knowledge of the transcription factors that specify tissue identity during normal embryonic development. Barrett's metaplasia describes the development of a columnar/intestinal phenotype in the squamous oesophageal epithelium and is the major risk factor for oesophageal adenocarcinoma. This particular type of cancer has a rapidly rising incidence and a dismal prognosis. The homoeotic transcription factor Cdx2 (Caudal-type homeobox 2) has been implicated as a master switch gene for intestine and therefore for Barrett's metaplasia. Normally, Cdx2 expression is restricted to the epithelium of the small and large intestine. Loss of Cdx2 function, or conditional deletion in the intestine, results in replacement of intestinal cells with a stratified squamous phenotype. In additi! on, Cdx2 is sufficient to provoke intestinal metaplasia in the stomach. In the present paper, we review the evidence for the role of Cdx2 in the development of Barrett's metaplasia. PMID: 20298184 [PubMed - in process] | | |
| Barrett's metaplasia: molecular mechanisms and nutritional influences.
March 20, 2010 at 6:55 AM
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| | Barrett's metaplasia: molecular mechanisms and nutritional influences. Biochem Soc Trans. 2010 Apr 1;38(2):313-9 Authors: Slack JM, Colleypriest BJ, Quinlan JM, Yu WY, Farrant MJ, Tosh D Barrett's metaplasia is discussed in the context of a general theory for the formation of metaplasias based on developmental biology. The phenotype of a particular tissue type becomes established during embryonic development by the expression of a specific set of transcription factors. If this combination becomes altered, then the tissue type can be altered. Such events may occur by mutation or by environmental effects on gene expression, normally within the stem cell population of the tissue. A macroscopic patch of metaplastic tissue will arise only if the new gene activity state is self-sustaining in the absence of its original causes, and if the new tissue type can outgrow the parent tissue type. An important candidate gene for the causation of Barrett's metaplasia is Cdx2 (Caudal-type homeobox 2). In normal development, this is expressed in the future intestine, but not the future foregut. Mouse knockout studies have shown that it is needed for intestinal deve! lopment, and that its loss from adult intestine can lead to squamous transformations. It is also expressed in Barrett's metaplasia and can be activated in oesophageal cell cultures by treatment with bile acids. We have investigated the ability of Cdx2 to bring about intestinal transformations in oesophageal epithelium. Our results show that Cdx2 can activate a programme of intestinal gene expression when overexpressed in HET-1A cells, or in fetal epithelium, but not in the adult epithelium. This suggests that Cdx2, although necessary for formation of intestinal tissue, is not sufficient to provoke Barrett's metaplasia in adult life and that overexpression of additional transcription factors is necessary. In terms of diet and nutrition, there is a known association of Barrett's metaplasia with obesity. This may work through an increased risk of gastro-oesophageal reflux. Acid and bile are known to activate Cdx2 expression in oesophageal cells. It may also increase circulatin! g levels of TNFalpha (tumour necrosis factor alpha), which act! ivates C dx2. In addition, there may be effects of diet on the composition of the bile. PMID: 20298175 [PubMed - in process] | | |
| The effects of rapid- or intermediate-acting insulin on the proliferation and differentiation of cultured chondrocytes.
March 20, 2010 at 6:55 AM
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| | The effects of rapid- or intermediate-acting insulin on the proliferation and differentiation of cultured chondrocytes. Curr Aging Sci. 2010 Feb;3(1):26-33 Authors: Iwata K, Asawa Y, Fujihara Y, Tanaka Y, Nishizawa S, Nakagawa T, Nagata S, Takato T, Hoshi K In cartilage regenerative medicine, which is highly expected in the face of our aging society, insulin is the potent factor for culture media. To secure the safety of culture media, we attempted to use medical insulin formulations, and compared their effects on human articular or auricular chondrocytes between regular human insulin (R) and neutral protamine hagedorn insulin (N). In monolayer culture with the media containing either R or N, the cell growth reached approximately 15-fold-increase in 6 days, which showed no significant difference between them. These cells showed the equivalent ability to produce cartilage matrices, both in vitro and in vivo. Also, in the 3D culture of the dedifferentiated chondrocytes, either R or N increased gene expression of type II collagen at 3-4 folds in the combination with other growth factors, compared with basal medium, while insulin could similarly enhance both the redifferentiation and cartilage maturation. The in vitro ha! lf-life of each insulin in the presence of chondrocytes neither decreased within 3 days, suggesting little degradation in the culture media, unlike in the body. Although both R and N showed similar biological effects on cultured chondrocytes, we may choose the R for clinical practice because of its pure composition. PMID: 20298167 [PubMed - in process] | | |
| Wound care advancements bring bevy of products.
March 20, 2010 at 6:55 AM
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| | Wound care advancements bring bevy of products. Mater Manag Health Care. 2010 Feb;19(2):18-20 Authors: DeJohn P Over the past several years, the nearly $2 billion post-surgical woundcare market has been inundated with devices designed to accelerate healing and prevent infection. For materials managers, wound care nurses and others involved in product selection, keeping up with the changes can be a challenge. Here wound care experts, manufacturers and other sources highlight some of the many recent product advances and their applications. In addition, sources comment on the field of regenerative medicine and where it may be headed. PMID: 20297620 [PubMed - in process] | | |
| Hydroxyapatite nanoparticles as a controlled-release carrier of BMP-2: absorption and release kinetics in vitro.
March 20, 2010 at 6:36 AM
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| | Hydroxyapatite nanoparticles as a controlled-release carrier of BMP-2: absorption and release kinetics in vitro. J Mater Sci Mater Med. 2010 Mar 19; Authors: Xie G, Sun J, Zhong G, Liu C, Wei J Recently, nanoparticles have been extensively developed as controlled-release carriers; however, there has been little research on hydroxyapatite nanoparticles (HANPs) and their potential applications. In this study, HANPs were investigated as a controlled-release carrier of bone morphogenetic protein-2 (BMP-2), the absorption and release kinetics of which were analyzed in vitro. Different concentrations of BMP-2 solution were used to evaluate the adsorptive properties of HANPs. It was observed that the amount of BMP-2 adsorbed onto HANPs could be as high as 70 mug/mg and that adsorption rate was highly correlated with the concentration of BMP-2 solution used. After absorption, the suspension of HANPs absorbed BMP-2 (HANPs/BMP-2) was incubated at 37 degrees C for 15 days and the release kinetics of BMP-2 from HANPs/BMP-2 was determined daily. The release profile showed sustained release of BMP-2 over the period of the investigation. Collectively, these results sug! gest that HANPs has the potential to function as a carrier for drug delivery systems and as a scaffold material in bone tissue engineering. PMID: 20300953 [PubMed - as supplied by publisher] | | |
| A Review of Multi-Responsive Membranous Systems for Rate-Modulated Drug Delivery.
March 20, 2010 at 6:36 AM
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| | A Review of Multi-Responsive Membranous Systems for Rate-Modulated Drug Delivery. AAPS PharmSciTech. 2010 Mar 19; Authors: Shaikh RP, Pillay V, Choonara YE, du Toit LC, Ndesendo VM, Bawa P, Cooppan S Membrane technology is broadly applied in the medical field. The ability of membranous systems to effectively control the movement of chemical entities is pivotal to their significant potential for use in both drug delivery and surgical/medical applications. An alteration in the physical properties of a polymer in response to a change in environmental conditions is a behavior that can be utilized to prepare 'smart' drug delivery systems. Stimuli-responsive or 'smart' polymers are polymers that upon exposure to small changes in the environment undergo rapid changes in their microstructure. A stimulus, such as a change in pH or temperature, thus serves as a trigger for the release of drug from membranous drug delivery systems that are formulated from stimuli-responsive polymers. This article has sought to review the use of stimuli-responsive polymers that have found application in membranous drug delivery systems. Polymers responsive to pH and temperature have been ! extensively addressed in this review since they are considered the most important stimuli that may be exploited for use in drug delivery, and biomedical applications such as in tissue engineering. In addition, dual-responsive and glucose-responsive membranes have been also addressed as membranes responsive to diverse stimuli. PMID: 20300895 [PubMed - as supplied by publisher] | | |
| Compressed collagen gel as the scaffold for skin engineering.
March 20, 2010 at 6:36 AM
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| | Compressed collagen gel as the scaffold for skin engineering. Biomed Microdevices. 2010 Mar 19; Authors: Hu K, Shi H, Zhu J, Deng D, Zhou G, Zhang W, Cao Y, Liu W Collagen gel scaffolds can potentially be utilized as cell seeded systems for skin tissue engineering. However, its dramatic contraction after being mixed with cells and its mechanical weakness are the drawbacks for its application to skin engineering. In this study, a compressed collagen gel scaffold was fabricated through the rapid expulsion of liquid from reconstituted gels by the application of 'plastic compression'(PC) technique. Both compressed and uncompressed gels were characterized with their gel contraction rate, morphology, the viability of seeded cells, their mechanical properties and the feasibility as a scaffold for constructing tissue-engineered skin. The results showed that the compression could significantly reduce the contraction of the collagen gel and improve its mechanical property. In addition, seeded dermal fibroblasts survived well in the compressed gel and seeded epidermal cells gradually developed into a stratified epidermal layer, and th! us formed tissue engineered skin. This study reveals the potential of using compressed collagen gel as a scaffold for skin engineering. PMID: 20300856 [PubMed - as supplied by publisher] | | |
| Peptide Interfacial Biomaterials Improve Endothelial Cell Adhesion and Spreading on Synthetic Polyglycolic Acid Materials.
March 20, 2010 at 6:36 AM
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| | Peptide Interfacial Biomaterials Improve Endothelial Cell Adhesion and Spreading on Synthetic Polyglycolic Acid Materials. Ann Biomed Eng. 2010 Mar 19; Authors: Huang X, Zauscher S, Klitzman B, Truskey GA, Reichert WM, Kenan DJ, Grinstaff MW Resorbable scaffolds such as polyglycolic acid (PGA) are employed in a number of clinical and tissue engineering applications owing to their desirable property of allowing remodeling to form native tissue over time. However, native PGA does not promote endothelial cell adhesion. Here we describe a novel treatment with hetero-bifunctional peptide linkers, termed "interfacial biomaterials" (IFBMs), which are used to alter the surface of PGA to provide appropriate biological cues. IFBMs couple an affinity peptide for the material with a biologically active peptide that promotes desired cellular responses. One such PGA affinity peptide was coupled to the integrin binding domain, Arg-Gly-Asp (RGD), to build a chemically synthesized bimodular 27 amino acid peptide that mediated interactions between PGA and integrin receptors on endothelial cells. Quartz crystal microbalance with dissipation monitoring (QCMD) was used to determine the association constant (K (A) 1 x 10(7! ) M(-1)) and surface thickness (~3.5 nm). Cell binding studies indicated that IFBM efficiently mediated adhesion, spreading, and cytoskeletal organization of endothelial cells on PGA in an integrin-dependent manner. We show that the IFBM peptide promotes a 200% increase in endothelial cell binding to PGA as well as 70-120% increase in cell spreading from 30 to 60 minutes after plating. PMID: 20300848 [PubMed - as supplied by publisher] | | |
| [A pilot study of three dimensional printing of human bone marrow stem cells (hBMSCs).]
March 20, 2010 at 6:36 AM
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| | [A pilot study of three dimensional printing of human bone marrow stem cells (hBMSCs).] Shanghai Kou Qiang Yi Xue. 2010 Feb;19(1):77-80 Authors: Chai G, Zhang Y, Liu QH, Ma SX, Hu QX, Cui L, Cao YL PURPOSE: To establish a three-dimensional biological printing technique of hBMSCs. METHODS: The hBMSCs were regularly isolated and cultured, and adjusted to the density of 1x10(6)/mL single cell suspension. Then these cells were labeled by PI fluorescence marker, and transferred by rapid prototype biological printer. Deposition spots were 300mum apart at X-axis, 500mum at Y-axis, 50mum at Z-axis, and then observed by laser confocal microscope. RESULTS: This technique could deposit cells with good spatial control. In three-dimensional layer, each "cell ink" drop contained 15-35 hBMSCs post-transfer, and achieved accurate distribution with spots distributed 300mum apart at x-axis, 500mum at y-axis and 50mum at Z-axis. CONCLUSIONS: This study indicates that hBMSCs can be effectively delivered by a rapid prototype printer with speed and accuracy. Application of three dimensional printing is of great importance in tissue engineering bone. Supported by National Natural ! Science Foundation of China (Grant No.30600650). PMID: 20300699 [PubMed - in process] | | |
| Modulation of Hepatocarcinoma Cell Morphology and Activity by Parylene-C Coating on PDMS.
March 20, 2010 at 6:36 AM
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| | Modulation of Hepatocarcinoma Cell Morphology and Activity by Parylene-C Coating on PDMS. PLoS One. 2010;5(3):e9667 Authors: Pereira-Rodrigues N, Poleni PE, Guimard D, Arakawa Y, Sakai Y, Fujii T BACKGROUND: The ability to understand and locally control the morphogenesis of mammalian cells is a fundamental objective of cell and developmental biology as well as tissue engineering research. We present parylene-C (ParC) deposited on polydimethylsiloxane (PDMS) as a new substratum for in vitro advanced cell culture in the case of Human Hepatocarcinoma (HepG2) cells. PRINCIPAL FINDINGS: Our findings establish that the intrinsic properties of ParC-coated PDMS (ParC/PDMS) influence and modulate initial extracellular matrix (ECM; here, type-I collagen) surface architecture, as compared to non-coated PDMS substratum. Morphological changes induced by the presence of ParC on PDMS were shown to directly affect liver cell metabolic activity and the expression of transmembrane receptors implicated in cell adhesion and cell-cell interaction. These changes were characterized by atomic force microscopy (AFM), which elucidated differences in HepG2 cell adhesion, spreading, ! and reorganization into two- or three-dimensional structures by neosynthesis of ECM components. Local modulation of cell aggregation was successfully performed using ParC/PDMS micropatterns constructed by simple microfabrication. CONCLUSION/SIGNIFICANCE: We demonstrated for the first time the modulation of HepG2 cells' behavior in relation to the intrinsic physical properties of PDMS and ParC, enabling the local modulation of cell spreading in a 2D or 3D manner by simple microfabrication techniques. This work will provide promising insights into the development of cell-based platforms that have many applications in the field of in vitro liver tissue engineering, pharmacology and therapeutics. PMID: 20300511 [PubMed - in process] | | |
| Microenvironment modulates osteogenic cell lineage commitment in differentiated embryonic stem cells.
March 20, 2010 at 6:36 AM
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| | Microenvironment modulates osteogenic cell lineage commitment in differentiated embryonic stem cells. PLoS One. 2010;5(3):e9663 Authors: Yamashita A, Nishikawa S, Rancourt DE BACKGROUND: Due to their self-renewal, embryonic stem cells (ESCs) are attractive cells for applications in regenerative medicine and tissue engineering. Although ESC differentiation has been used as a platform for generating bone in vitro and in vivo, the results have been unsatisfactory at best. It is possible that the traditional culture methods, which have been used, are not optimal and that other approaches must be explored. METHODOLOGY/PRINCIPAL FINDINGS: ESCs were differentiated into osteoblast lineage using a micro-mass approach. In response to osteogenic differentiation medium, many cells underwent apoptosis, while others left the micro-mass, forming small aggregates in suspension. These aggregates were cultured in three different culture conditions (adhesion, static suspension, and stirred suspension), then examined for osteogenic potential in vitro and in vivo. In adhesion culture, ESCs primed to become osteoblasts recommitted to the adipocyte lineage i! n vitro. In a static suspension culture, resulting porous aggregates expressed osteoblasts markers and formed bone in vivo via intermembranous ossification. In a stirred suspension culture, resulting non-porous aggregates suppressed osteoblast differentiation in favor of expanding progenitor cells. CONCLUSIONS/SIGNIFICANCE: We demonstrate that microenvironment modulates cell fate and subsequent tissue formation during ESC differentiation. For effective tissue engineering using ESCs, it is important to develop optimized cell culture/differentiation conditions based upon the influence of microenvironment. PMID: 20300192 [PubMed - in process] | | | | 
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