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| Immunology Grants: CIRM Gives $25 Million to 19 Researchers
June 22, 2010 at 9:44 PM
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| Directors of the California stem cell agency today approved $25 million for immunology research, overturning four negative decisions by its grant reviewers.
Directors faced a record nine public petitions to reverse its reviewers. After some grumbling, the directors, who see only a summary of the application and reviewer comments, okayed the four.
Successful petitioners included Jeanne Loring | | |
| CIRM Board Moves to Closed Door Session
June 22, 2010 at 5:29 PM
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| | Directors of the California stem cell agency have moved into an executive session to consider confidential items in applications for $30 million in funding for immunology research. It is unclear when the public session will resume, but our guess in an hour or so. | | |
| Correction
June 22, 2010 at 5:20 PM
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| | We incorrectly reported in three earlier items that 45 applications for immunology items were received by CIRM and 16 approved. Actually, 44 were received and 15 approved. | | |
| CIRM Board Begins Consideration of Immunology Grants
June 22, 2010 at 5:12 PM
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| The board of the Californiai stem cell agency has begun its open session with consideration of $30 million in grants for immunology research. Nine rejected candidates are seeking reconsideration of their applications.
Following consideration of the grants, Chairman Robert Klein said the board would the report by President Alan Trounson. | | |
| CIRM Board in Executive Session
June 22, 2010 at 2:34 PM
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| The board of the California stem cell agency this morning promptly went into executive session but may begins its open meeting by about 1:30 p.m. or 2 p.m. PDT.
We plan to resume monitoring the meeting again at that point. If you are attempting to listen to the Internet audiocast, you should be hearing music but no voices. The executive sessions are usually in a different room, and the audiocast | | |
| Scripps' Loring on CIRM Grant Petitions
June 22, 2010 at 1:51 PM
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| Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute, filed a comment today that shed some additional light on the nine petitions that are seeking to overturn negative decisions on their grant applications.
Loring, who has served on grant review committees with the NIH, said,
"I don't think the intention of any of the petitioners was to subvert the | | |
| Positive contrast imaging of iron oxide nanoparticles with susceptibility-weighted imaging.
June 22, 2010 at 7:16 AM
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| | Positive contrast imaging of iron oxide nanoparticles with susceptibility-weighted imaging. Magn Reson Med. 2010 Jun 17; Authors: Eibofner F, Steidle G, Kehlbach R, Bantleon R, Schick F Superparamagnetic iron oxide particles can be utilized to label cells for immune cell and stem cell therapy. The labeled cells cause significant field distortions induced in their vicinity, which can be detected with magnetic resonance imaging (MRI). In conventional imaging, the signal voids arising from the field distortions lead to negative contrast, which is not desirable, as detection of the cells can be masked by native low signal tissue. In this work, a new method for visualizing magnetically labeled cells with positive contrast is proposed and described. The technique presented is based on the susceptibility-weighted imaging (SWI) post-processing algorithm. Phase images from gradient-echo sequences are evaluated pixel by pixel, and a mask is created with values ranging from 0 to 1, depending on the phase value of the pixel. The magnitude image is then multiplied by the mask. With an appropriate mask function, positive contrast in the vicinity of the labeled cells is created. The feasibility of this technique is proved using an agar phantom containing superparamagnetic iron oxide particles-labeled cells and an ex vivo bovine liver. The results show high potential for detecting even small labeled cell concentrations in structurally inhomogeneous tissue types. Magn Reson Med, 2010. (c) 2010 Wiley-Liss, Inc. PMID: 20564596 [PubMed - as supplied by publisher] | | |
| Personalizing Stem Cell Research and Therapy: The Arduous Road Ahead or Missed Opportunity?
June 22, 2010 at 7:16 AM
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| | Personalizing Stem Cell Research and Therapy: The Arduous Road Ahead or Missed Opportunity? Curr Pharmacogenomics Person Med. 2010 Mar 1;8(1):25-36 Authors: Patel SA, King CC, Lim PK, Habiba U, Dave M, Porecha R, Rameshwar P The euphoria of stem cell therapy has diminished, allowing scientists, clinicians and the general public to seriously re-examine how and what types of stem cells would effectively repair damaged tissue, prevent further tissue damage and/or replace lost cells. Importantly, there is a growing recognition that there are substantial person-to-person differences in the outcome of stem cell therapy. Even though the small molecule pharmaceuticals have long remained a primary focus of the personalized medicine research, individualized or targeted use of stem cells to suit a particular individual could help forecast potential failures of the therapy or identify, early on, the individuals who might benefit from stem cell interventions. This would however demand collaboration among several specialties such as pharmacology, immunology, genomics and transplantation medicine. Such transdisciplinary work could also inform how best to achieve efficient and predictable stem cell migration to sites of tissue damage, thereby facilitating tissue repair. This paper discusses the possibility of polarizing immune responses to rationalize and individualize therapy with stem cell interventions, since generalized "one-size-fits-all" therapy is difficult to achieve in the face of the diverse complexities posed by stem cell biology. We also present the challenges to stem cell delivery in the context of the host related factors. Although we focus on the mesenchymal stem cells in this paper, the overarching rationale can be extrapolated to other types of stem cells as well. Hence, the broader purpose of this paper is to initiate a dialogue within the personalized medicine community by expanding the scope of inquiry in the field from pharmaceuticals to stem cells and related cell-based health interventions. PMID: 20563265 [PubMed - as supplied by publisher] | | |
| Injections of Adipose Tissue-Derived Stem Cells and Stem Cell Lysate Improve Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury.
June 22, 2010 at 7:16 AM
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| | Injections of Adipose Tissue-Derived Stem Cells and Stem Cell Lysate Improve Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury. J Sex Med. 2010 Jun 17; Authors: Albersen M, Fandel TM, Lin G, Wang G, Banie L, Lin CS, Lue TF ABSTRACT Introduction. Erectile dysfunction (ED) remains a major complication after radical prostatectomy. The use of adipose tissue-derived stem cells (ADSCs) has shown promising results for the treatment of ED. However, the mechanisms of action for stem cell therapy remain controversial, with increasing evidence pointing to paracrine pathways. Aim. To determine the effects and to identify the mechanism of action of ADSC and ADSC-derived lysate in a rat model of cavernous nerve (CN) crush injury. Methods. Thirty-two male Sprague-Dawley rats were randomly divided into four equal groups: one group underwent sham operation, while three groups underwent bilateral CN crush. Crush-injury groups were treated at the time of injury with intracavernous injection of ADSC, lysate, or vehicle only (injured controls). Erectile function was assessed by CN electrostimulation at 4 weeks. Penile tissue was collected for histology. Main Outcome Measures. Intracavernous pressure increase upon CN stimulation; neuronal nitric oxide synthase (nNOS) content in the dorsal penile nerve; smooth muscle content, collagen content, and number of apoptotic cells in the corpus cavernosum. Results. Both ADSC and lysate treatments resulted in significant recovery of erectile function, as compared with vehicle treatment. nNOS content was preserved in both the ADSC and lysate group, with significantly higher expression compared with vehicle-treated animals. There was significantly less fibrosis and a significant preservation of smooth muscle content in the ADSC and lysate groups compared with injured controls. The observed functional improvement after lysate injection supports the hypothesis that ADSCs act through release of intracellular preformed substances or by active secretion of certain biomolecules. The underlying mechanism of recovery appears to involve neuron preservation and cytoprotection by inhibition of apoptosis. Conclusions. Penile injection of both ADSC and ADSC-derived lysate can improve recovery of erectile function in a rat model of neurogenic ED. Albersen M, Fandel TM, Lin G, Wang G, Banie L, Lin CS, and Lue TF. Injections of adipose tissue-derived stem cells and stem cell lysate improve recovery of erectile function in a rat model of cavernous nerve injury. J Sex Med **;**:**-**. PMID: 20561166 [PubMed - as supplied by publisher] | | |
| Mesenchymal stem cell therapy for chronic renal failure.
June 22, 2010 at 7:16 AM
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| | Mesenchymal stem cell therapy for chronic renal failure. Expert Opin Biol Ther. 2010 Jun 19; Authors: Choi SJ, Kim JK, Hwang SD Importance of the field: Chronic kidney disease (CKD) has become a worldwide public health problem. Renal transplantation is the treatment of choice for end-stage renal disease, but is limited by a small number of organ donors and the immune barrier. To overcome these problems, new therapeutic strategies for tissue repair have recently emerged. Areas covered in this review: We discuss the therapeutic potential of mesenchymal stem cells (MSCs) in kidney injury and examine the latest reports providing evidence supporting MSC efficacy in the treatment of chronic renal failure (CRF). What the reader will gain: MSCs improve histological and functional outcomes in various CRF model systems. Paracrine effects rather than transdifferentiation might result in the prevention of progressive renal failure. In addition, MSCs can reprogram kidney cell differentiation, and modulate neo-kidney transplantation in CRF. Take home message: Although many practical problems remain to be addressed, treatment with MSCs will enter the mainstream of CRF treatment. PMID: 20560782 [PubMed - as supplied by publisher] | | |
| SOFT-MI: A novel microfabrication technique integrating soft-lithography and molecular imprinting for tissue engineering applications.
June 22, 2010 at 6:46 AM
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| | SOFT-MI: A novel microfabrication technique integrating soft-lithography and molecular imprinting for tissue engineering applications. Biotechnol Bioeng. 2010 Mar 26;106(5):804-817 Authors: Vozzi G, Morelli I, Vozzi F, Andreoni C, Salsedo E, Morachioli A, Giusti P, Ciardelli G An innovative approach has been employed for the realization of bioactive scaffolds able to mimic the in vivo cellular microenvironment for tissue engineering applications. This method is based on the combination of molecular imprinting and soft-lithography technology to enhance cellular adhesion and to guide cell growth and proliferation due to presence of highly specific recognition sites of selected biomolecules on a well-defined polymeric microstructure. In this article polymethylmethacrylate (PMMA) scaffolds have been realized by using poly(dimethylsiloxane) (PDMS) microstructured molds imprinted with FITC-albumin and TRITC-lectin. In addition gelatin, an adhesion protein, was employed for the molecular imprinting of polymeric scaffolds for cellular tests. The most innovative aspect of this research was the molecular imprinting of whole cells for the development of substrates able to enhance the cell adhesion processes. Biotechnol. Bioeng. 2010;106: 804-817. (c) 2010 Wiley Periodicals, Inc. PMID: 20564617 [PubMed - as supplied by publisher] | | |
| Systemic effect of Fructus Psoraleae extract on bone in mice.
June 22, 2010 at 6:46 AM
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| | Systemic effect of Fructus Psoraleae extract on bone in mice. Phytother Res. 2010 Jun 7; Authors: Wong RW, Rabie AB Fructus Psoraleae extract is used in China for the treatment of bone diseases. The objective of the study was to investigate the systemic effect of Fructus Psoraleae extract consumption on bone histomorphology. Sixteen 8-week-old male BALB/c mice were divided into control and experimental groups. In the control group, eight mice were fed daily with distilled water. In the experimental group, eight mice were fed daily with distilled water mixed with Fructus Psoraleae extract. The mice were kept for 5 weeks and then killed. Using micro-computed tomography, 20 micro-tomographic slices with a separation of 0.25 mm were acquired to cover the proximal end of the left tibia of each mouse. Quantitative morphometry of the bone structure was performed. The results showed that consumption of Fructus Psoraleae extract significantly increased the bone volume/tissue volume ratio by 11.8%. The bone trabeculae increased by 7.1% in thickness so that the bone density was increased. To conclude, Fructus Psoraleae extract taken orally increases bone density and alters bone histomorphology. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20564544 [PubMed - as supplied by publisher] | | |
| Simvastatin induces osteogenic differentiation of murine embryonic stem cells.
June 22, 2010 at 6:46 AM
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| | Simvastatin induces osteogenic differentiation of murine embryonic stem cells. J Bone Miner Res. 2010 Jun 18; Authors: Pagkalos J, Cha JM, Kang Y, Heliotis M, Tsiridis E, Mantalaris A Statins are potent inhibitors of cholesterol synthesis. Several statins are available with different molecular and pharmacokinetic properties. Simvastatin is more lipophilic than pravastatin and has a higher affinity to phospholipid membranes than atorvastatin allowing its passive diffusion through the cell membrane. In vitro studies on bone marrow stromal cells, osteoblast-like cells, and embryonic stem cells have shown statins to have cholesterol-independent anabolic effects on bone metabolism; alas statins were supplemented in osteogenic media which does not facilitate the elucidation of their potential osteoinductive properties. Embryonic stem cells (ESC), derived from the inner cell mass of the blastocyst, have the unique properties of perpetual self-proliferation as well as being pluripotent and able to differentiate towards all the cellular lineages composing the body, including the osteogenic lineage. Consequently, ESCs represent a potentially potent cell source for future clinical cellular therapies of various bone diseases, even though there are several hurdles that still need to be overcome. Herein, we demonstrate, for the first time to our knowledge, that simvastatin induces murine ESC (mESC) differentiation towards the osteogenic lineage in the absence of osteoinductive supplements. Specifically, we found that a simvastatin concentration in the microM range and higher was toxic to the cells and that effective concentration for osteoinduction was 0.1 nM as shown by increased alizarin red staining as well as increased osteocalcin and osetrix gene expression. These results suggest that lipophylic simvastatin may in the future provide a novel pharmacological agent for bone tissue engineering applications. (c) 2010 American Society for Bone and Mineral Research. PMID: 20564244 [PubMed - as supplied by publisher] | | |
| Biological activity of laminin peptide conjugated alginate and chitosan Matrices.
June 22, 2010 at 6:46 AM
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| | Biological activity of laminin peptide conjugated alginate and chitosan Matrices. Biopolymers. 2010 May 24; Authors: Yamada Y, Hozumi K, Katagiri F, Kikkawa Y, Nomizu M Laminin active peptide conjugated chitosan mambranes have been previously demonstrated as a useful biomaterial for tissue engineering. Here, three laminin active peptides, A99 (AGTFALRGDNPQG), AG73 (RKRLQVQLSIRT), and EF1zz (ATLQLQEGRLHFXFDLGKGR, X: Nle), which interact with integrin alphavbeta3, syndecans, and integrin alpha2beta1, respectively, were conjugated to alginate and evaluated the biological activities. A99-alginate (3 - 3000 ng/mm(2)) promoted cell attachment depending on the amount of alginate. More than 300 ng/mm(2) of the A99-alginate matrices effectively promoted cell attachment, cell spreading with well-organized actin stress fibers, and neurite outgrowth. AG73- and EF1zz-alginates promoted strong cell attachment at the all amounts (3 - 3000 ng/mm(2)). A99-alginate (30 - 3000 ng/mm(2)) promoted strong neurite outgrowth but lower amounts of A99-alginate (3 ng/mm(2)) showed weak activity. In contrast, AG73-alginates (3 - 30 ng/mm(2)) showed strong neurite outgrowth activity but higher amounts of AG73-alginate (300 - 3000 ng/mm(2)) decreased the activity. These data indicate that neurite outgrowth activity of peptide-alginate matrices is peptide specific and the activity is dependent on the amount of alginate. Further, biological activities of the peptides on alginate and chitosan matrices were different, suggesting that the integrin- and syndecan-mediated cellular functions on the peptide-matrices are highly influenced by the scaffold structure including polysaccharide types and amounts. The laminin active peptide conjugated alginate and chitosan matrices can control receptor type specific functions and are useful for tissue engineering. (c) 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2010. PMID: 20564024 [PubMed - as supplied by publisher] | | |
| Patterned growth of vertically aligned silicon nanowire arrays for label-free DNA detection using surface-enhanced Raman spectroscopy.
June 22, 2010 at 6:46 AM
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| | Patterned growth of vertically aligned silicon nanowire arrays for label-free DNA detection using surface-enhanced Raman spectroscopy. Anal Bioanal Chem. 2010 Jun 20; Authors: Yi C, Li CW, Fu H, Zhang M, Qi S, Wong NB, Lee ST, Yang M Patterning is of paramount importance in many areas of modern science and technology. As a good candidate for novel nanoscale optoelectronics and miniaturized molecule sensors, vertically aligned silicon nanowire (SiNW) with controllable location and orientation is highly desirable. In this study, we developed an effective procedure for the fabrication of vertically aligned SiNW arrays with micro-sized features by using single-step photolithography and silver nanoparticle-induced chemical etching at room temperature. We demonstrated that the vertically aligned SiNW arrays can be used as a platform for label-free DNA detection using surface-enhanced Raman spectroscopy (SERS), where the inherent "fingerprint" SERS spectra allows for the differentiation of closely related biospecies. Since the SiNW array patterns could be modified by simply varying the mask used in the photolithographic processing, it is expected that the methodology can be used to fabricate label-free DNA microarrays and may be applicable to tissue engineering, which aims to create living tissue substitutes from cells seeded onto 3D scaffolds. PMID: 20563793 [PubMed - as supplied by publisher] | | |
| A comparison of the tissue response to chronically implanted Parylene-C-coated and uncoated planar silicon microelectrode arrays in rat cortex.
June 22, 2010 at 6:46 AM
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| | A comparison of the tissue response to chronically implanted Parylene-C-coated and uncoated planar silicon microelectrode arrays in rat cortex. Biomaterials. 2010 Jun 17; Authors: Winslow BD, Christensen MB, Yang WK, Solzbacher F, Tresco PA In this study we employed a quantitative immunohistochemical approach to compare the brain tissue response to planar silicon microelectrode arrays that were conformally coated with Parylene-C to uncoated controls at 2, 4, and 12 weeks following implantation into the cortex of adult male Sprague-Dawley rats. We did not find any difference in the relative intensity or the spatial distribution of neuronal or glial markers over the indwelling period, even though Parylene-C-coated substrates supported significantly less cell attachment, indicating that the foreign body response to planar silicon microelectrode arrays has little to do with the composition or decomposition of the silicon electrode. Moreover, our results suggest that changes in microelectrode surface chemistry do not have a strong influence on the cytoarchitectural changes that accompany the brain foreign body response to planar silicon microelectrode arrays. Our quantitative comparison over the indwelling period does not support progressive increases in astrocyte encapsulation and/or progressive neuronal loss in the recording zone as dominant failure mechanisms of the type of chronic recording device. Finally, we found evidence of two potentially new failure mechanisms that were associated with CD68 immunoreactivity including demyelination of adjacent neurons and BBB breakdown surrounding implanted electrodes at long indwelling times. PMID: 20561678 [PubMed - as supplied by publisher] | | |
| Preparation of Caco-2 cell sheets using plasma polymerised acrylic acid as a weak boundary layer.
June 22, 2010 at 6:46 AM
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| | Preparation of Caco-2 cell sheets using plasma polymerised acrylic acid as a weak boundary layer. Biomaterials. 2010 Jun 17; Authors: Majani R, Zelzer M, Gadegaard N, Rose FR, Alexander MR The use of cell sheets for tissue engineering applications has considerable advantages over single cell seeding techniques. So far, only thermoresponsive surfaces have been used to manufacture cell sheets without chemically disrupting the cell-surface interactions. Here, we present a new and facile technique to prepare sheets of epithelial cells using plasma polymerised acrylic acid films. The cell sheets are harvested by gentle agitation of the media without the need of any additional external stimulus. We demonstrate that the plasma polymer deposition conditions affect the viability and metabolic activity of the cells in the sheet and relate these effects to the different surface properties of the plasma polymerised acrylic acid films. Based on surface analysis data, a first attempt is made to explain the mechanism behind the cell sheet formation. The advantage of the epithelial cell sheets generated here over single cell suspensions to seed a PLGA scaffold is presented. The scaffold itself, prepared using a mould fabricated via photolithography, exhibits a unique architecture that mimics closely the dimensions of the native tissue (mouse intestine). PMID: 20561676 [PubMed - as supplied by publisher] | | |
| Effects of the architecture of tissue engineering scaffolds on cell seeding and culturing.
June 22, 2010 at 6:46 AM
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| | Effects of the architecture of tissue engineering scaffolds on cell seeding and culturing. Acta Biomater. 2010 Jun 15; Authors: Melchels FP, Barradas AM, van Blitterswijk CA, de Boer J, Feijen J, Grijpma DW The advance of rapid prototyping techniques has significantly improved control over the pore network architecture of tissue engineering scaffolds. In this work we assessed the influence of scaffold pore architecture on cell seeding and static culturing, by comparing a computer-designed gyroid architecture fabricated by stereolithography to a random-pore architecture resulting from salt-leaching. The scaffold types showed comparable porosity and pore size values, but the gyroid type showed a more than tenfold higher permeability due to the absence of size-limiting pore interconnections. The higher permeability significantly improved the wetting properties of the hydrophobic scaffolds, and increased the settling speed of cells upon static seeding of immortalised mesenchymal stem cells. After dynamic seeding followed by 5 days of static culture, gyroid scaffolds showed large cell populations in the centre of the scaffold, while salt-leached scaffolds were covered with a cell-sheet on the outside and no cells were found in the scaffold centre. It was shown that interconnectivity of the pores and permeability of the scaffold prolongs the time of static culture before overgrowth of cells at the scaffold periphery occurs. Furthermore, novel scaffold designs are proposed to further improve the transport of oxygen and nutrients throughout the scaffolds, and to create tissue engineering grafts with designed, pre-fabricated vasculature. PMID: 20561602 [PubMed - as supplied by publisher] | | |
| Synthesis and Characterization of Degradable Bioconjugated Hydrogels with Hyperbranched Multifunctional Crosslinkers.
June 22, 2010 at 6:46 AM
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| | Synthesis and Characterization of Degradable Bioconjugated Hydrogels with Hyperbranched Multifunctional Crosslinkers. Acta Biomater. 2010 Jun 15; Authors: Pedrón S, Peinado C, Bosch P, S Anseth K Hyperbranched poly(ester amide) polymer (Hybrane S1200; M(n) 1200 g/mol) was functionalized with maleic anhydride (MA) and propylene sulfide, to obtain multifunctional crosslinkers with fumaric and thiol-end groups, S1200MA and S1200SH, respectively. The degree of substitution of maleic acid groups (DS) was controlled by varying the molar ratio of MA to S1200 in the reaction mixture. Hydrogels were obtained by UV crosslinking of functionalized S1200 and poly(ethyleneglycol) diacrylate (PEGDA) in aqueous solutions. Compressive modulus increased with decreasing the S1200/PEG ratio and also depended on the DS of the multifunctional crosslinker (S1200). Also, heparin-based macromonomers together with functionalized hyperbranched polymers were used to construct novel functional hydrogels. The multivalent hyperbranched polymers allowed high crosslinking densities in heparin modified gels while introducing biodegradation sites. Both heparin presence and acrylate/thiol ratio have an impact on degradation profiles and morphologies. Hyperbranched crosslinked hydrogels showed no evidence of cell toxicity. Overall, the multifunctional crosslinkers afford hydrogels with promising properties that suggest that these may be suitable for tissue engineering applications. PMID: 20561601 [PubMed - as supplied by publisher] | | |
| Chemically-Conjugated Bone Morphogenetic Protein-2 on Three-Dimensional Polycaprolactone (PCL) Scaffolds Stimulates Osteogenic Activity in Bone Marrow Stromal Cells.
June 22, 2010 at 6:46 AM
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| | Chemically-Conjugated Bone Morphogenetic Protein-2 on Three-Dimensional Polycaprolactone (PCL) Scaffolds Stimulates Osteogenic Activity in Bone Marrow Stromal Cells. Tissue Eng Part A. 2010 Jun 18; Authors: Zhang H, Migneco F, Lin CY, Hollister S Polycaprolactone (PCL) has received considerable attention in bone tissue engineering. However, the lack of osteoinductive ability of PCL limits its application. The aim of this study was to directly attach bone morphogenetic protein-2 (BMP-2) to PCL scaffolds by a cross-linking conjugation method and to investigate whether the bound BMP-2 maintained bioactivity in vitro. Immunofluorescent staining against BMP-2 and quantitative Enzyme-linked immunosorbent assay (ELISA) measurements demonstrated that BMP-2 was successfully immobilized on the PCL three-dimensional scaffold by aminolysis and subsequent chemical conjugation. Conjugation produced much higher immobilization efficiency than the physical adsorption. Conjugated BMP-2 release from the PCL scaffolds was significantly slower than that from BMP-2-adsorbed PCL scaffolds over 15 days, which resulted in more BMP-2 locally retained on the conjugated scaffold. Furthermore, the downstream Smads pathway was up-regulated in bone marrow stromal cells (BMSCs) cultured on the BMP-2 conjugated PCL scaffolds. Finally, gene expressions of osteogenic marker (alkaline phosphotase, osteoclacin, type I collagen) were up-regulated in BMSCs cultured on the PCL scaffolds with BMP-2 conjugation, but not on PCL scaffolds after BMP-2 adsorption. Therefore, our finding demonstrated BMP2 conjugation on polyester scaffolds is a feasible way to impart scaffolds with osteoinductive capability. PMID: 20560772 [PubMed - as supplied by publisher] | | |
| [How to elongate healthy life expectancy. Let's start anti-aging]
June 22, 2010 at 6:46 AM
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| | [How to elongate healthy life expectancy. Let's start anti-aging] Hokkaido Igaku Zasshi. 2010 May;85(3):157-60 Authors: Majima T, Koyama T, Houkinn K, Tohyama H, Nakagawa S To elongate healthy life expectancy, anti-aging action is important. Main causes of disease in aged patients who need to be cared are cerebral artery disease, bone and joint disease, and dementia. It is important to enlighten the method to prevent these diseases. In the present symposium, we explained etiology and prevention of these diseases. We hope that the symposium would help the attendee to understand how to elongate the healthy life expectancy. PMID: 20560414 [PubMed - in process] | | |
| A polydioxanone electrospun valved patch to replace the right ventricular outflow tract in a growing lamb model.
June 22, 2010 at 6:46 AM
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| | A polydioxanone electrospun valved patch to replace the right ventricular outflow tract in a growing lamb model. Biomaterials. 2010 May;31(14):4056-63 Authors: Kalfa D, Bel A, Chen-Tournoux A, Della Martina A, Rochereau P, Coz C, Bellamy V, Bensalah M, Vanneaux V, Lecourt S, Mousseaux E, Bruneval P, Larghero J, Menasché P A major issue in congenital heart surgery is the lack of viable right ventricular outflow tract (RVOT) replacement materials. Several biomaterials have been used, with different scaffolds and cells, but they have failed to restore a tri-layered RVOT, and reoperations are often required. We investigated the function, histological changes and potential of growth and tissue regeneration of polydioxanone (PDO) electrospun bioabsorbable valved patches seeded with mesenchymal stem cells (MSCs) in the RVOT of growing lambs. Autologous blood-derived MSCs were labeled with quantum dots and seeded on PDO electrospun valved patches. Those were implanted into the RVOT of 6 growing lambs followed up until 8 months. Results were assessed by echocardiography, magnetic resonance imaging (MRI), histology, immunohistochemistry and biochemical assays. Tissue-engineered RVOT were neither stenotic nor aneurismal and displayed a growth potential, with less fibrosis, less calcifications and no thrombus compared with control polytetrafluoroethylene (PTFE)-pericardial patches. The PDO scaffold was completely degraded and replaced by a viable, three-layered, endothelialized tissue and an extracellular matrix with elastic fibers similar to that of native tissue. Detection of quantum dots at 1 month suggested that at least some of the cells were-derived from the grafted cells. A polydioxanone electrospun tissue-engineered valved transannular patch seems to be a promising device in restoring a living RVOT and could ultimately lead to applications in the treatment of congenital RVOT diseases. PMID: 20181391 [PubMed - indexed for MEDLINE] | | |
| An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart.
June 22, 2010 at 6:46 AM
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| | An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart. Biomaterials. 2010 May;31(14):3885-93 Authors: Chen QZ, Ishii H, Thouas GA, Lyon AR, Wright JS, Blaker JJ, Chrzanowski W, Boccaccini AR, Ali NN, Knowles JC, Harding SE We hypothesize that a combinatorial approach of ventricle constraint and stem cell therapy would offer a greater benefit for the treatment of heart failure than either strategy alone. A heart patch would serve two therapeutic purposes: biomechanical support and cell delivery. In this study, we describe a hybrid heart patch engineered from a synthetic elastomer, poly(glycerol sebacate) (PGS), supplemented with cardiomyocytes differentiated from human embryonic stem cells (hESCs). In line with two therapeutically relevant considerations, i.e. biocompatibility and cell delivery efficiency, the PGS was (a) pre-conditioned in culture medium for 6 days, and (b) prepared without gelatin coatings to facilitate detachment and delivery of cardiomyocytes following patch implantation. Following pre-conditioning under physiological conditions, the PGS patch material without gelatin coating was found to satisfactorily support cardiomyocyte viability and attachment, with active cell beating for periods of longer than 3 months until interrupted. Dynamic culture studies revealed that cells detached more efficiently from the uncoated surface of PGS than from gelatin-coated PGS. No significant differences were detected between the beating rates of human embryonic stem cell-derived cardiomyocytes on tissue culture plate and the pre-conditioned and gelatin-uncoated PGS. PGS patches sutured over the left ventricle of rats in vivo remained intact over a 2 week period without any deleterious effects on ventricular function. We conclude that PGS is a suitable biomaterial for stem cell-based regeneration strategies to restore cardiomyocyte function, and the hybrid heart patch engineered under optimal conditions would be a promising support device for the cardiac repair. PMID: 20153041 [PubMed - indexed for MEDLINE] | | |
| Human umbilical cord stem cell encapsulation in calcium phosphate scaffolds for bone engineering.
June 22, 2010 at 6:46 AM
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| | Human umbilical cord stem cell encapsulation in calcium phosphate scaffolds for bone engineering. Biomaterials. 2010 May;31(14):3848-57 Authors: Zhao L, Weir MD, Xu HH Human bone marrow mesenchymal stem cells (hBMSCs) require an invasive procedure to harvest, and have lower self-renewal potential with aging. Umbilical cord mesenchymal stem cells (hUCMSCs) are a relatively new stem cell source; this study reveals a self-setting and load-bearing calcium phosphate construct that encapsulates these stem cells. The flexural strength (mean+/-sd; n=5) of the hUCMSC-encapsulating calcium phosphate cement (CPC) increased from (3.5+/-1.1) MPa without polyglactin fibers, to (11.7+/-2.1) MPa with 20% of polyglactin fibers (p<0.05). hUCMSCs attached to the bone mineral-mimicking scaffold in the osteogenic media and differentiated down the osteogenic lineage, yielding elevated alkaline phosphatase (ALP) and osteocalcin (OC) gene expressions. ALP and OC on the CPC-fiber scaffold was 2-fold those on CPC control without fibers. hUCMSCs encapsulated inside the scaffolds retained excellent viability and cell density. The encapsulated hUCMSCs inside four different constructs successfully differentiated down the osteogenic lineage and synthesized bone minerals, as confirmed by mineral staining, SEM, and XRD. The percentage of mineral area synthesized by the encapsulated hUCMSCs increased from about 3% at day-7, to 12% at day-21 (p<0.05). In conclusion, this study demonstrated that hUCMSCs encapsulated in the bioengineered scaffolds osteo-differentiated and synthesized bone minerals. The self-setting CPC-chitosan-fiber scaffold supported the viability and osteogenic differentiation of the encapsulated hUCMSCs, and had mechanical strength matching that of cancellous bone. PMID: 20149437 [PubMed - indexed for MEDLINE] | | |
| Identification of a potential modification site in human stromal cell-derived factor-1.
June 22, 2010 at 6:43 AM
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| | Identification of a potential modification site in human stromal cell-derived factor-1. Biopolymers. 2010 May 24; Authors: Baumann L, Beck-Sickinger AG Selective modification of proteins is an important tool to study their function. However, it is still challenging to identify the best position in order to avoid a loss of activity. By using an Nvoc-modification approach we facilitate the identification of a potential modification site as Nvoc can be removed in situ by UV irradiation and accordingly allows directly the comparison of the biological activity of the modified and the unmodified protein derived from the same precursor. As a test system, we used stromal cell-derived factor-1, which is involved in a wide range of physiological functions, mainly haematopoiesis and embryonic organ development. This chemokine is a potential candidate in regenerative medicine due to its capability to attract stem cells to distinct localizations. First, we synthesized the wildtype and the Nvoc-modified C-terminal segments SDF-1(50-68) and studied their secondary structure formation by circular dichroism spectroscopy. By using the IMPACT((R)) system we then expressed the peptide thioester M-[A(49)]-SDF-1(1-49)-MESNA recombinantly, in which the valine at position 49 was replaced by a more suitable alanine residue to allow improved cleavage and ligation. After ligation and refolding, the biological activity was proven in a cell-based IP(3) accumulation assay prior and after Nvoc removal, which showed that neither the alanine 49 nor the attached Nvoc group impair the activity of the analogue. The study shows, that lysine 56 is a potential site to introduce labels site-specifically in SDF-1. (c) 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2010. PMID: 20564039 [PubMed - as supplied by publisher] | | |
| Challenges and strategies for generating therapeutic patient-specific hemangioblasts and hematopoietic stem cells from human pluripotent stem cells.
June 22, 2010 at 6:43 AM
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| | Challenges and strategies for generating therapeutic patient-specific hemangioblasts and hematopoietic stem cells from human pluripotent stem cells. Int J Dev Biol. 2010 Jun 4; Authors: Peters A, Burridge PW, Pryzhkova MV, Levine MA, Park TS, Roxbury C, Yuan X, Peault B, Zambidis ET Recent characterization of hemangioblasts differentiated from human embryonic stem cells (hESC) has further confirmed evidence from murine, zebrafish and avian experimental systems that hematopoietic and endothelial lineages arise from a common progenitor. Such progenitors may provide a valuable resource for delineating the initial developmental steps of human hemato-endotheliogenesis, which is a process normally difficult to study due to the very limited accessibility of early human embryonic/fetal tissues. Moreover, efficient hemangioblast and hematopoietic stem cell (HSC) generation from patient-specific pluripotent stem cells has enormous potential for regenerative medicine, since it could lead to strategies for treating a multitude of hematologic and vascular disorders. However, significant scientific challenges remain in achieving these goals, and the generation of transplantable hemangioblasts and HSC derived from hESC currently remains elusive. Our previous work has suggested that the failure to derive engraftable HSC from hESC is due to the fact that current methodologies for differentiating hESC produce hematopoietic progenitors developmentally similar to those found in the human yolk sac, and are therefore too immature to provide adult-type hematopoietic reconstitution. Herein, we outline the nature of this challenge and propose targeted strategies for generating engraftable human pluripotent stem cell-derived HSC from primitive hemangioblasts using a developmental approach. We also focus on methods by which reprogrammed somatic cells could be used to derive autologous pluripotent stem cells, which in turn could provide unlimited sources of patient-specific hemangioblasts and HSC. PMID: 20563986 [PubMed - as supplied by publisher] | | | | 
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