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| Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study.
March 26, 2010 at 7:55 AM
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| | Clinical effectiveness of an acellular dermal regenerative tissue matrix compared to standard wound management in healing diabetic foot ulcers: a prospective, randomised, multicentre study. Int Wound J. 2009 Jun;6(3):196-208 Authors: Reyzelman A, Crews RT, Moore JC, Moore L, Mukker JS, Offutt S, Tallis A, Turner WB, Vayser D, Winters C, Armstrong DG This 12-week, prospective, randomised, controlled multi-centre study compared the proportion of healed diabetic foot ulcers and mean healing time between patients receiving acellular matrix (AM) (study group) and standard of care (control group) therapies. Eighty-six patients were randomised into study (47 patients) and control (39 patients) groups. No significant differences in demographics or pre-treatment ulcer data were calculated. Complete healing and mean healing time were 69.6% and 5.7 weeks, respectively, for the study group and 46.2% and 6.8 weeks, respectively, for the control group. The proportion of healed ulcers between the groups was statistically significant (P = 0.0289), with odds of healing in the study group 2.7 times higher than in the control group. Kaplan-Meier survivorship analysis for time to complete healing at 12 weeks showed a significantly higher non healing rate (P = 0.015) for the control group (53.9%) compared with the study group (30! .4%). After adjusting for ulcer size at presentation, which was a statistically significant covariate (P = 0.0194), a statistically significant difference in non healing rate between groups was calculated (P = 0.0233), with odds of healing 2.0 times higher in the study versus control group. This study supports the use of single-application AM therapy as an effective treatment of diabetic, neuropathic ulcers. PMID: 19368581 [PubMed - indexed for MEDLINE] | | |
| Microfluidic platforms for studies of angiogenesis, cell migration, and cell-cell interactions. Sixth International Bio-Fluid Mechanics Symposium and Workshop March 28-30, 2008 Pasadena, California.
March 26, 2010 at 7:55 AM
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| | Microfluidic platforms for studies of angiogenesis, cell migration, and cell-cell interactions. Sixth International Bio-Fluid Mechanics Symposium and Workshop March 28-30, 2008 Pasadena, California. Ann Biomed Eng. 2010 Mar;38(3):1164-77 Authors: Chung S, Sudo R, Vickerman V, Zervantonakis IK, Kamm RD Recent advances in microfluidic technologies have opened the door for creating more realistic in vitro cell culture methods that replicate many aspects of the true in vivo microenvironment. These new designs (i) provide enormous flexibility in controlling the critical biochemical and biomechanical factors that influence cell behavior, (ii) allow for the introduction of multiple cell types in a single system, (iii) provide for the establishment of biochemical gradients in two- or three-dimensional geometries, and (iv) allow for high quality, time-lapse imaging. Here, some of the recent developments are reviewed, with a focus on studies from our own laboratory in three separate areas: angiogenesis, cell migration in the context of tumor cell-endothelial interactions, and liver tissue engineering. PMID: 20336839 [PubMed - in process] | | |
| Mussel adhesive protein fused with cell adhesion recognition motif triggers integrin-mediated adhesion and signaling for enhanced cell spreading, proliferation, and survival.
March 26, 2010 at 7:55 AM
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| | Mussel adhesive protein fused with cell adhesion recognition motif triggers integrin-mediated adhesion and signaling for enhanced cell spreading, proliferation, and survival. J Biomed Mater Res A. 2010 Mar 24; Authors: Kim BJ, Choi YS, Choi BH, Lim S, Song YH, Cha HJ Adhesion of cells to a surface is a basic and important requirement in the fields of cell culture and tissue engineering. Previously, we constructed the cell adhesive, fp-151-RGD, by fusion of the hybrid mussel adhesive protein, fp-151, and GRGDSP peptide, one of the major cell adhesion recognition motifs; fp-151-RGD efficiently immobilized cells on coated culture surfaces with no protein and surface modifications, and apparently enhanced cell adhesion, proliferation, and spreading abilities. In the present study, we investigated the potential use of fp-151-RGD as a biomimetic extracellular matrix material at the molecular level by elucidating its substantial effects on integrin-mediated adhesion and signaling. Apoptosis derived from serum deprivation was significantly suppressed on the fp-151-RGD-coated surface, indicating that RGD-induced activation of integrin-mediated signaling triggers the pathway for cell survival. Analysis of the phosphorylation of focal ad! hesion kinase clearly demonstrated activation of focal adhesion kinase, a well-established indicator of integrin-mediated signaling, on the fp-151-RGD-coated surface, leading to significantly enhanced cell behaviors, including proliferation, spreading and survival, and consequently, more efficient cell culture. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20336754 [PubMed - as supplied by publisher] | | |
| Three-dimensional macroscopic scaffolds with a gradient in stiffness for functional regeneration of interfacial tissues.
March 26, 2010 at 7:55 AM
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| | Three-dimensional macroscopic scaffolds with a gradient in stiffness for functional regeneration of interfacial tissues. J Biomed Mater Res A. 2010 Mar 24; Authors: Singh M, Dormer N, Salash JR, Christian JM, Moore DS, Berkland C, Detamore MS A novel approach has been demonstrated to construct biocompatible, macroporous 3-D tissue engineering scaffolds containing a continuous macroscopic gradient in composition that yields a stiffness gradient along the axis of the scaffold. Polymeric microspheres, made of poly(D,L-lactic-co-glycolic acid) (PLGA), and composite microspheres encapsulating a higher stiffness nano-phase material (PLGA encapsulating CaCO(3) or TiO(2) nanoparticles) were used for the construction of microsphere-based scaffolds. Using controlled infusion of polymeric and composite microspheres, gradient scaffolds displaying an anisotropic macroscopic distribution of CaCO(3)/TiO(2) were fabricated via an ethanol sintering technique. The controllable mechanical characteristics and biocompatible nature of these scaffolds warrants further investigation for interfacial tissue engineering applications. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20336753 [PubMed - as supplied by publisher] | | |
| Novel poly(L-lactic acid)/hyaluronic acid macroporous hybrid scaffolds: Characterization and assessment of cytotoxicity.
March 26, 2010 at 7:55 AM
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| | Novel poly(L-lactic acid)/hyaluronic acid macroporous hybrid scaffolds: Characterization and assessment of cytotoxicity. J Biomed Mater Res A. 2010 Mar 24; Authors: Antunes JC, Oliveira JM, Reis RL, Soria JM, Gómez-Ribelles JL, Mano JF Poly(L-lactic acid), PLLA, a synthetic biodegradable polyester, is widely accepted in tissue engineering. Hyaluronic acid (HA), a natural polymer, exhibits an excellent biocompatibility, influences cell signaling, proliferation, and differentiation. In this study, HA crosslinking was performed by immersion of the polysaccharide in water-acetone mixtures containing glutaraldehyde (GA). The objective of this work is to produce PLLA scaffolds with the pores coated with HA, that could be beneficial for bone tissue engineering applications. PLLA tridimensional scaffolds were prepared by compression molding followed by salt leaching. After the scaffolds impregnation with soluble HA solutions of distinct concentration, a GA-crosslinking reaction followed by inactivation of the unreacted GA with glycine was carried out. An increase on surface roughness is shown by scanning electron microscopy (SEM) with the addition of HA. Toluidine blue staining indicates the present of ! stable crosslinked HA. An estimation of the HA original weight in the hybrid scaffolds was performed using thermal gravimetric analyses. FTIR-ATR and XPS confirmed the crosslinking reaction. Preliminary in vitro cell culture studies were carried out using a mouse lung fibroblast cell line (L929). SEM micrographs of L929 showed that cells adhered well, spread actively throughout all scaffolds, and grew favorably. A MTS test indicated that cells were viable when cultured onto the surface of all scaffolds, suggesting that the introduction of crosslinked HA did not increase the cytotoxicity of the hybrid scaffolds. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20336752 [PubMed - as supplied by publisher] | | |
| Evaluation of scaffold materials for tooth tissue engineering.
March 26, 2010 at 7:55 AM
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| | Evaluation of scaffold materials for tooth tissue engineering. J Biomed Mater Res A. 2010 Mar 24; Authors: Ohara T, Itaya T, Usami K, Ando Y, Sakurai H, Honda MJ, Ueda M, Kagami H Recently, the possibility of tooth tissue engineering has been reported. Although there are a number of available materials, information about scaffolds for tooth tissue engineering is still limited. To improve the manageability of tooth tissue engineering, the effect of scaffolds on in vivo tooth regeneration was evaluated. Collagen and fibrin were selected for this study based on the biocompatibility to dental papilla-derived cells and the results were compared with those of polyglycolic acid (PGA) fiber and beta-tricalcium phosphate (beta-TCP) porous block, which are commonly used for tooth, dentin and bone tissue engineering. Isolated porcine tooth germ-derived cells were seeded onto one of those scaffolds and transplanted to the back of nude mice. Tooth bud-like structures were observed more frequently in collagen and fibrin gels than on PGA or beta-TCP, while the amount of hard tissue formation was less. The results showed that collagen and fibrin gel suppor! t the initial regeneration process of tooth buds possibly due to their ability to support the growth of epithelial and mesenchymal cells. On the other hand, maturation of tooth buds was difficult in fibrin and collagen gels, which may require other factors. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20336748 [PubMed - as supplied by publisher] | | |
| PLGA conduit seeded with olfactory ensheathing cells for bridging sciatic nerve defect of rats.
March 26, 2010 at 7:55 AM
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| | PLGA conduit seeded with olfactory ensheathing cells for bridging sciatic nerve defect of rats. J Biomed Mater Res A. 2010 Mar 24; Authors: Li BC, Jiao SS, Xu C, You H, Chen JM PLGA is thought to be a promising material for nerve scaffold. OECs have been shown to promote axon outgrowth and myelination following peripheral nerve transection. This study assessed the compatibility between PLGA and OECs in vitro, and evaluated the effect of PLGA conduit filled with OECs and extracellular matrix gel (ECM) (POE group) on 10 mm-defect sciatic nerve of rats. Silicon-OECs-EMC (SOE group), PLGA-ECM (PE group), and silicon-ECM (SE group)-were used as the controls. The survival and distribution of OECs in vivo, neurohistology and neurofunction of the bridged nerve, were quantitatively evaluated from 1 week to 12 weeks after surgery. PLGA possessed complete compatibility with OECs. After implantation, OECs migrated along the axis of the nerve and survived longer in the POE group than in the SOE group. Gross recovery of the animal, like ulcerious and autophagical rate as well as relative diameter recovery rate of the fiber, was more successful in the ! POE group than in other groups. The number of the fiber in the middle and distal segments of bridged sites and neurons in anterior horn of the spinal cord was increased in both OECs-contained groups, but the diameter and the myeline thickness of the fiber were increased only in the POE group. The nerve conduction velocity and the amplitude of compound muscle active potential were improved much successfully in the PLGA-guided group than in the silicon-guided group, but the best improvement was encountered in the POE group. Sciatic function index was not improved in all groups at 12 weeks after surgery due to the injury model. These results suggested that PLGA filled with OECs is a significant alternative to conventional autograft in repairing peripheral nerve defects, and OECs are potential seed cells for peripheral nerve tissue engineering. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20336740 [PubMed - as supplied by publisher] | | |
| Human adipose-derived stem cells (hASCs) proliferate and differentiate in osteoblast-like cells on trabecular titanium scaffolds.
March 26, 2010 at 7:55 AM
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| | Human adipose-derived stem cells (hASCs) proliferate and differentiate in osteoblast-like cells on trabecular titanium scaffolds. J Biomed Mater Res A. 2010 Mar 24; Authors: Gastaldi G, Asti A, Scaffino MF, Visai L, Saino E, Cometa AM, Benazzo F The use of stem cells in regenerative medicine is an appealing area of research that has received a great deal of interest in recent years. The population called human adipose tissue-derived stem cells (hASCs) share many of the characteristic of its counterpart of marrow including extensive proliferative potential and the ability to undergo multilineage differentiation along classical mesenchymal lineages: adipogenesis, chondrogenesis, osteogenesis, and myogenesis. The aim of this study was to evaluate with biochemical and morphological methods the adhesion and differentiation of hASCs grown on trabecular titanium scaffolds. The hASCs isolated from subcutaneous adipose tissue after digestion with collagenase were seeded on monolayer and on trabecular titanium scaffolds and incubated at 37 degrees C in 5% CO(2) with osteogenic medium or control medium.The results showed that hASCs were able to adhere to titanium scaffolds, to proliferate, to acquire an osteoblastic! -like phenotype, and to produce a calcified extracellular matrix with protein, such as, decorin, fibronectin, osteocalcin, osteonectin, osteopontin, and type I collagen. These data suggest that this kind of scaffold/cells construct is effective to regenerate damaged tissue and to restore the function of bone tissue. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20336739 [PubMed - as supplied by publisher] | | |
| Articular cartilage tissue engineering based on a mechano-active scaffold made of poly(L-lactide-co-epsilon-caprolactone): In vivo performance in adult rabbits.
March 26, 2010 at 7:55 AM
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| | Articular cartilage tissue engineering based on a mechano-active scaffold made of poly(L-lactide-co-epsilon-caprolactone): In vivo performance in adult rabbits. J Biomed Mater Res B Appl Biomater. 2010 Mar 24; Authors: Xie J, Han Z, Naito M, Maeyama A, Kim SH, Kim YH, Matsuda T Our previous studies showed that a mechano-active scaffold made of poly(L-lactide-co-epsilon-caprolactone) (PLCL) exhibited a high potential to realize the formation of a functional, engineered cartilage in vitro. This animal study therefore was designed to investigate the feasibility of repairing on osteochondral defect with the use of bone marrow-derived mesenchymal stem cells (BMSCs) incorporated with a PLCL scaffold. Rabbit BMSCs, isolated and subsequently cultured in monolayer, were seeded into a porous PLCL scaffold sponge following an implantation onto a full-thickness osteochondral defect (diameter of 4.5 mm, depth of 5 mm) that was artificially created on the medial femoral condyles at a high load-bearing site on a rabbit's knee joint. Time-dependent healing of the defect was evaluated by macroscopic, histological examinations at both 3- and 6-month-implantations, respectively. A PLCL sponge incorporated with BMSCs exhibited sufficient structural support,! resulting in new osteochondral tissue regeneration: a physiologically well-integrated subchondral bone formation, a hyaline cartilage-like morphology containing chondrocytes surrounded by abundant cartilaginous matrices. In addition, quantitative biochemical assays also demonstrated high potential for the synthesis of sulfated glycosaminoglycan and collagen, both of which are biomolecules essential to extracelluar matrix in normal cartilage tissue. In contrast, defects filled with cell-free PLCL scaffold or left empty showed a very limited potential for regeneration. Our findings suggest that a composite of PLCL-based sponge scaffold and BMSCs promote the repair of osteochondral defects at high load-bearing sites in adult rabbits. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20336738 [PubMed - as supplied by publisher] | | |
| Repairing goat tibia segmental bone defect using scaffold cultured with mesenchymal stem cells.
March 26, 2010 at 7:55 AM
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| | Repairing goat tibia segmental bone defect using scaffold cultured with mesenchymal stem cells. J Biomed Mater Res B Appl Biomater. 2010 Mar 24; Authors: Liu X, Li X, Fan Y, Zhang G, Li D, Dong W, Sha Z, Yu X, Feng Q, Cui F, Watari F In this study, we investigated cellular biocompatibility in vitro and segmental bone defect repairing efficacy in vivo of a previously reported fibre-reinforced scaffold, nano-hydroxyapatite/collagen/poly (L-lactic acid) (PLLA)/chitin fibres (nHACP/CF). First, attachment, proliferation, and differentiation of the goat bone mesenchymal stem cells (GBMSCs) cultured on the nHACP/CF scaffolds were evaluated in vitro. The results showed that cells attached to the scaffolds well, and there was no significant difference in cell proliferation between cells on the scaffolds and cells on the polystyrene culture plates that were used as a control. The results also showed that alkaline phosphatase (ALP)/DNA of the cells cultured on the scaffolds was significantly higher than that on the control. The in vivo study compared the bone defect repairing efficacy of nHACP/CF scaffolds with that of autograft bone. Thirty-two adult male goats with 25-mm defects in their tibias at the ! same anatomic site were divided into four groups. The first group was implanted with the nHACP/CF with GBMSCs. The second group was implanted with autograft bone. The third group was implanted with the nHACP/CF. Nothing was implanted in the fourth group. Bone growth was evaluated by radiography, histology, and biomechanics. The results showed that although the nHACP/CF had new bone formation, it could not repair the defect fully while nHACP/CF with GBMSCs cultured and autograft bone could repair the segmental bone defect by 8 weeks after surgery, suggesting that nHACP/CF is an appropriate scaffold for bone tissue engineering. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20336727 [PubMed - as supplied by publisher] | | |
| FGF signalling as a mediator of lineage transitions-Evidence from embryonic stem cell differentiation.
March 26, 2010 at 7:55 AM
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| | FGF signalling as a mediator of lineage transitions-Evidence from embryonic stem cell differentiation. J Cell Biochem. 2010 Mar 24; Authors: Villegas SN, Canham M, Brickman JM The fibroblast growth factor (FGF) signalling pathway is one of the most ubiquitous in biology. It has diverse roles in development, differentiation and cancer. Embryonic stem (ES) cells are in vitro cell lines capable of differentiating into all the lineages of the conceptus. As such they have the capacity to differentiate into derivatives of all three germ layers and to some extent the extra-embryonic lineages as well. Given the prominent role of FGF signalling in early embryonic development, we explore the role of this pathway in early ES cell differentiation towards the major lineages of the embryo. As early embryonic differentiation is intricately choreographed at the level of morphogenetic movement, adherent ES cell culture affords a unique opportunity to study the basic steps in early lineage specification in the absence of ever shifting complex in vivo microenvironments. Thus recent experiments in ES cell differentiation are able to pinpoint specific FGF d! ependent lineage transitions that are difficult to resolve in vivo. Here we review the role of FGF signalling in early development alongside the ES cell data and suggest that FGF dependent signalling via phospho-Erk activation maybe a major mediator of transitions in lineage specification. J. Cell. Biochem. (c) 2010 Wiley-Liss, Inc. PMID: 20336694 [PubMed - as supplied by publisher] | | |
| Creating frog heart as an organ: in vitro-induced heart functions as a circulatory organ in vivo.
March 26, 2010 at 7:55 AM
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| | Creating frog heart as an organ: in vitro-induced heart functions as a circulatory organ in vivo. Int J Dev Biol. 2010 Jan 29; Authors: Kinoshita M, Ariizumi T, Yuasa S, Miyoshi S, Komazaki S, Fukuda K, Asashima M Cardiomyocytes have been induced from various pluripotent cells, such as embryonic stem cells and myeloid stem cells; however, the generation of cardiac tissues beyond two-dimensional cell-sheets has not been reported. Creating higher order, three-dimensional structures that are unique to heart is the long-awaited next step in realizing cardiac regenerative medicine. We have previously shown that cardiomyocytes can be induced in vitro from undifferentiated cells (animal caps) excised from Xenopus embryos. Cardiomyocytes were induced by first dissociating the animal caps and then reaggregating them following treatment with activin. Here, we describe an interesting method for creating a complete ectopic heart in vivo, involving the introduction of in vitro-created tissue during early embryogenesis. Thus, animal cap reaggregates were transplanted into the abdomen of late-neurula-stage embryos, resulting in two-chambered hearts being formed. The dual-heart larvae matu! red into adult animals with transplanted hearts intact. Involvement of transplanted hearts in systemic circulation was demonstrated. Moreover, the ectopic hearts possessed higher order structures such as atrium and ventricle, and were morphologically, histologically, and electrophysiologically identical to original hearts. This system should facilitate the study of heart organogenesis and may promote a shift from tissue to organ engineering for clinical applications. PMID: 20336605 [PubMed - as supplied by publisher] | | |
| Novel roles for Notch, Wnt and Hedgehog in hematopoesis derived from human pluripotent stem cells.
March 26, 2010 at 7:55 AM
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| | Novel roles for Notch, Wnt and Hedgehog in hematopoesis derived from human pluripotent stem cells. Int J Dev Biol. 2010 Mar 15; Authors: Cerdan C, Bhatia M Human pluripotent stem cells (PSCs) derived from a number of different sources, including reprogrammed adult somatic cells, provide a powerful cellular system to study signaling pathways implicated in cell fate decisions, and generate new sources of cells for regenerative medicine. To realize this potential, it is essential to control the direction and efficiency of human PSC differentiation. Although Notch, Wnt and Hedgehog (HH) signaling pathways have been implicated in the self-renewal/proliferation of hematopoietic stem/progenitor cells, both in vitro and in vivo, their roles in differentiation processes remain poorly explored. This review describes the role(s) of these pathways in the adult and embryonic hematopoietic system of mice and humans, with a particular emphasis on our recent studies on the hematopoietic development of human embryonic stem cells (hESCs). Understanding the individual and collective contributions of Notch, Wnt and HH signaling to the i! nitial development of hematopoiesis is critical for achieving successful ex vivo expansion and differentiation of hematopoietic stem cells (HSCs) from human PSCs that will retain bona fide function comparable to adult-derived HSCs. PMID: 20336604 [PubMed - as supplied by publisher] | | |
| In vitro reprogramming of pancreatic cells to hepatocytes.
March 26, 2010 at 7:55 AM
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| | In vitro reprogramming of pancreatic cells to hepatocytes. Methods Mol Biol. 2010;636:285-92 Authors: Eberhard D, O'Neill K, Burke ZD, Tosh D Transdifferentiation is defined as the conversion of one cell type to another. One well-documented example of transdifferentiation is the conversion of pancreatic cells to hepatocytes. Here we describe a robust in vitro model to study pancreas to liver transdifferentiation. It is based on the addition of the synthetic glucocorticoid dexamethasone to the rat pancreatic exocrine cell line AR42J. Following glucocorticoid treatment, cells resembling hepatocytes are induced. Transdifferentiated hepatocytes express many of the properties of bona fide hepatocytes, e.g. production of albumin and ability to respond to xenobiotics. These hepatocytes can be used for studying liver function in vitro as well as studying the molecular basis of transdifferentiation. PMID: 20336529 [PubMed - in process] | | |
| Adult cell fate reprogramming: converting liver to pancreas.
March 26, 2010 at 7:55 AM
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| | Adult cell fate reprogramming: converting liver to pancreas. Methods Mol Biol. 2010;636:251-83 Authors: Meivar-Levy I, Ferber S Regenerative medicine aims at producing new cells for repair or replacement of diseased and damaged tissues. Embryonic and adult stem cells have been suggested as attractive sources of cells for generating the new cells needed. The leading dogma was that adult cells in mammals, once committed to a specific lineage, become "terminally differentiated" and can no longer change their fate. However, in recent years increasing evidence has accumulated demonstrating the remarkable ability of some differentiated cells to be converted into a different cell type via a process termed developmental redirection or adult cells reprogramming. For example, abundant human cell types, such as dermal fibroblasts and adipocytes, could potentially be harvested and converted into other, medically important cell types, such as neurons, cardiomyocytes, or pancreatic beta cells. In this chapter, we describe a method of activating the pancreatic lineage and beta-cells function in adult hum! an liver cells by ectopic expression of pancreatic transcription factors. This approach aims to generate custom-made autologous surrogate beta cells for treatment of diabetes, and possibly bypass both the shortage of cadaveric human donor tissues and the need for life-long immune-suppression. PMID: 20336528 [PubMed - in process] | | |
| Transplantation of human mesenchymal stem cells in the study of neuropathic pain.
March 26, 2010 at 7:55 AM
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| | Transplantation of human mesenchymal stem cells in the study of neuropathic pain. Methods Mol Biol. 2010;617:337-45 Authors: Siniscalco D Neuropathic pain is a complex disease that involves several molecular pathways. Due to its individual character, the treatment of neuropathic pain is extremely difficult. Currently available drugs do not affect the mechanisms underlying the generation and propagation of pain. Therefore, pain research is now focused on molecular approaches such as stem cell therapy. Stem cells mediate neuroprotection in a variety of nervous system injury models. We used spared nerve injury (SNI) model of neuropathic pain to assess the possible use of human mesenchymal stem cells (hMSCs) as neuroprotective tool in the regenerative medicine. We conclude that stem cell transplantation could be a useful therapeutic tool in the future of regenerative medicine. PMID: 20336433 [PubMed - in process] | | |
| Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation.
March 26, 2010 at 7:55 AM
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| | Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature. 2010 Mar 25;464(7288):606-9 Authors: Jopling C, Sleep E, Raya M, Martí M, Raya A, Belmonte JC Although mammalian hearts show almost no ability to regenerate, there is a growing initiative to determine whether existing cardiomyocytes or progenitor cells can be coaxed into eliciting a regenerative response. In contrast to mammals, several non-mammalian vertebrate species are able to regenerate their hearts, including the zebrafish, which can fully regenerate its heart after amputation of up to 20% of the ventricle. To address directly the source of newly formed cardiomyocytes during zebrafish heart regeneration, we first established a genetic strategy to trace the lineage of cardiomyocytes in the adult fish, on the basis of the Cre/lox system widely used in the mouse. Here we use this system to show that regenerated heart muscle cells are derived from the proliferation of differentiated cardiomyocytes. Furthermore, we show that proliferating cardiomyocytes undergo limited dedifferentiation characterized by the disassembly of their sarcomeric structure, detac! hment from one another and the expression of regulators of cell-cycle progression. Specifically, we show that the gene product of polo-like kinase 1 (plk1) is an essential component of cardiomyocyte proliferation during heart regeneration. Our data provide the first direct evidence for the source of proliferating cardiomyocytes during zebrafish heart regeneration and indicate that stem or progenitor cells are not significantly involved in this process. PMID: 20336145 [PubMed - in process] | | |
| Optical Monitoring During Bioreactor Conditioning of Tissue-Engineered Heart Valves.
March 26, 2010 at 7:55 AM
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| | Optical Monitoring During Bioreactor Conditioning of Tissue-Engineered Heart Valves. ASAIO J. 2010 Mar 22; Authors: Ziegelmueller JA, Zaenkert EK, Schams R, Lackermair S, Schmitz C, Reichart B, Sodian R Currently, one approach to tissue engineering has been to develop in vitro conditions to fabricate functional cardiovascular structures such as heart valves before final implantation. In vivo conditions are simulated using a bioreactor system that supplies cells with oxygen and culture media while providing mechanical stimulation to promote tissue maturation. In our experiment, we developed a novel combined optical monitoring and conditioning device. The entire system is made of acrylic glass and is completely transparent. The bioreactor is connected to an air-driven respirator pump, and the cell culture medium continuously closed-loop system. By adjusting stroke volume, stroke rate, and inspiration/expiration time of the ventilator, the system allows various pulsatile flows and different levels of pressure. Our optical monitoring and conditioning device provides a sterile environment, mechanical stimulation, and optical monitoring for the in vitro maturation of a! tissue-engineered heart valve. With the camera module attached, tissue-engineered valves can be observed during the entire in vitro phase. This setting helps to find the optimal dynamic conditions for tissue-engineered heart valves to mature by adjusting flow and pressure conditions to provide physiological opening and closing behavior of the heart valve construct. PMID: 20335802 [PubMed - as supplied by publisher] | | |
| Spontaneous In Vitro Transformation of Primary Human Osteoblast-like Cells.
March 26, 2010 at 7:55 AM
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| | Spontaneous In Vitro Transformation of Primary Human Osteoblast-like Cells. Cancer Genomics Proteomics. 2010 Mar-Apr;7(2):61-6 Authors: Magdolen U, Schmitt M, Hildebrandt B, Diehl P, Schauwecker J, Saldamli B, Burgkart R, Tübel J, Gradinger R, Royer-Pokora B BACKGROUND: Two new tumor-like cell lines were established which developed spontaneously in vitro from normal human primary osteoblast-like cells originating from non-oncogenic bone surgery. MATERIALS AND METHODS: The tumor cell properties studied included morphology, proliferation characteristics in normal and low-serum media, and anchorage-independent growth in soft agarose. Results and CONCLUSION: Karyotyping of the cells showed numerous rearrangements and abnormalities. These results pointed to the tumorigenic potential of the cells and demonstrate the importance of biosafety in tissue engineering and therapeutic cell applications when prolonged culture conditions are required. PMID: 20335519 [PubMed - in process] | | |
| Evaluation of Cartilage Repair Tissue After Matrix-Associated Autologous Chondrocyte Transplantation Using a Hyaluronic-Based or a Collagen-Based Scaffold With Morphological MOCART Scoring and Biochemical T2 Mapping: Preliminary Results.
March 26, 2010 at 7:55 AM
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| | Evaluation of Cartilage Repair Tissue After Matrix-Associated Autologous Chondrocyte Transplantation Using a Hyaluronic-Based or a Collagen-Based Scaffold With Morphological MOCART Scoring and Biochemical T2 Mapping: Preliminary Results. Am J Sports Med. 2010 Mar 24; Authors: Welsch GH, Mamisch TC, Zak L, Blanke M, Olk A, Marlovits S, Trattnig S BACKGROUND: In cartilage repair, bioregenerative approaches using tissue engineering techniques have tried to achieve a close resemblance to hyaline cartilage, which might be visualized using advanced magnetic resonance imaging. PURPOSE: To compare cartilage repair tissue at the femoral condyle noninvasively after matrix-associated autologous chondrocyte transplantation using Hyalograft C, a hyaluronic-based scaffold, to cartilage repair tissue after transplantation using CaReS, a collagen-based scaffold, with magnetic resonance imaging using morphologic scoring and T2 mapping. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Twenty patients after matrix-associated autologous chondrocyte transplantation (Hyalograft C, n = 10; CaReS, n = 10) underwent 3-T magnetic resonance imaging 24 months after surgery. Groups were matched by age and defect size/localization. For clinical outcome, the Brittberg score was assessed. Morphologic analysis was applied using! the magnetic resonance observation of cartilage repair tissue score, and global and zonal biochemical T2 mapping was performed to reflect biomechanical properties with regard to collagen matrix/content and hydration. RESULTS: The clinical outcome was comparable in each group. The magnetic resonance observation of cartilage repair tissue score showed slightly but not significantly (P = .210) better results in the CaReS group (76.5) compared to the Hyalograft C group (70.0), with significantly better (P = .004) constitution of the surface of the repair tissue in the CaReS group. Global T2 relaxation times (milliseconds) for healthy surrounding cartilage were comparable in both groups (Hyalograft C, 49.9; CaReS, 51.9; P = .398), whereas cartilage repair tissue showed significantly higher results in the CaReS group (Hyalograft C, 48.2; CaReS, 55.5; P = .011). Zonal evaluation showed no significant differences (P >/= .05). CONCLUSION: Most morphologic parameters provided com! parable results for both repair tissues. However, differences ! in the s urface and higher T2 values for the cartilage repair tissue that was based on a collagen scaffold (CaReS), compared to the hyaluronic-based scaffold, indicated differences in the composition of the repair tissue even 2 years postimplantation. CLINICAL RELEVANCE: In the follow-up of cartilage repair procedures using matrix-associated autologous chondrocyte transplantation, differences due to scaffolds have to be taken into account. PMID: 20335510 [PubMed - as supplied by publisher] | | |
| Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure.
March 26, 2010 at 7:55 AM
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| | Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure. Auton Neurosci. 2010 Mar 22; Authors: Kimura K, Kanazawa H, Ieda M, Kawaguchi-Manabe H, Miyake Y, Yagi T, Arai T, Sano M, Fukuda K In severe congestive heart failure (CHF), sympathetic overactivity correlates with the exacerbation of cardiac performance. To test the hypothesis that the cardiac sympathetic nerve density dramatically changes with the acceleration of circulating norepinephrine (NE) concentration, we investigated the temporal association of nerve growth factor (NGF) expression in the heart and cardiac sympathetic nerve density during the development of CHF in the continuous NE-infused rats. The animals were analyzed at 0-, 1-, 3-, 7-, 14-, and 28-day after implantation of osmotic pump at a rate of 0.05mg/kg/hr. The cardiac performance was temporally facilitated in NE-exposed rats at 3-day in accordance with the sympathetic hyper-innervation induced by the augmentation of NGF mRNA expression in the heart. In NE-treated rats, left ventricular end-diastolic pressure was significantly increased after 7-day and marked left ventricular hypertrophy and systemic fluid retention were obse! rved at 28-day. CHF-induced sympathetic overactivity further increased plasma NE concentration in NE-treated rats and finally reached to 16.1+/-5.6ng/ml at 28-day (control level was 0.39+/-0.1ng/ml, p<0.01). In the decompensated CHF rats at 28-day, the NGF mRNA expression was conspicuously reduced concomitant with the obvious nerve fiber loss confirmed by the immunostaining of nerve axonal marker, PGP9.5 and sympathetic neuron marker, tyrosine hydroxylase. This resulted in the attenuated tissue NE contents and the exacerbating cardiac performance. The cardiac sympathetic fiber loss was also confirmed in NE-exposed DBH (dopamine beta-hydroxylase)-Cre/Floxed-EGFP (enhanced green fluorescent protein) mice with severe CHF, in which sympathetic nerve could be traced by EGFP. Our results suggest that the cardiac sympathetic nerve density is strictly regulated by the NGF expression in the heart and long-exposure of high plasma NE concentration caused myocardial NGF reduction, f! ollowing sympathetic fiber loss in severe CHF animals. PMID: 20335077 [PubMed - as supplied by publisher] | | |
| Mesenchymal stem cell therapy: Two steps forward, one step back.
March 26, 2010 at 7:55 AM
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| | Mesenchymal stem cell therapy: Two steps forward, one step back. Trends Mol Med. 2010 Mar 22; Authors: Ankrum J, Karp JM Mesenchymal stem cell (MSC) therapy is poised to establish a new clinical paradigm; however, recent trials have produced mixed results. Although MSC were originally considered to treat connective tissue defects, preclinical studies revealed potent immunomodulatory properties that prompted the use of MSC to treat numerous inflammatory conditions. Unfortunately, although clinical trials have met safety endpoints, efficacy has not been demonstrated. We believe the challenge to demonstrate efficacy can be attributed in part to an incomplete understanding of the fate of MSC following infusion. Here, we highlight the clinical status of MSC therapy and discuss the importance of cell-tracking techniques, which have advanced our understanding of the fate and function of systemically infused MSC and might improve clinical application. PMID: 20335067 [PubMed - as supplied by publisher] | | |
| Dipeptide-based polyphosphazene and polyester blends for bone tissue engineering.
March 26, 2010 at 7:55 AM
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| | Dipeptide-based polyphosphazene and polyester blends for bone tissue engineering. Biomaterials. 2010 Mar 22; Authors: Deng M, Nair LS, Nukavarapu SP, Jiang T, Kanner WA, Li X, Kumbar SG, Weikel AL, Krogman NR, Allcock HR, Laurencin CT Polyphosphazene-polyester blends are attractive materials for bone tissue engineering applications due to their controllable degradation pattern with non-toxic and neutral pH degradation products. In our ongoing quest for an ideal completely miscible polyphosphazene-polyester blend system, we report synthesis and characterization of a mixed-substituent biodegradable polyphosphazene poly[(glycine ethyl glycinato)(1)(phenyl phenoxy)(1)phosphazene] (PNGEG/PhPh) and its blends with a polyester. Two dipeptide-based blends namely 25:75 (Matrix1) and 50:50 (Matrix2) were produced at two different weight ratios of PNGEG/PhPh to poly(lactic acid-glycolic acid) (PLAGA). Blend miscibility was confirmed by differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Both blends resulted in higher tensile modulus and strength than the polyester. The blends showed a degradation rate in the order of Matrix2<Matrix1<PLAGA in ! phosphate buffered saline at 37 degrees C over 12 weeks. Significantly higher pH values of degradation media were observed for blends compared to PLAGA confirming the neutralization of PLAGA acidic degradation by polyphosphazene hydrolysis products. The blend components PLAGA and polyphosphazene exhibited a similar degradation pattern as characterized by the molecular weight loss. Furthermore, blends demonstrated significantly higher osteoblast growth rates compared to PLAGA while maintaining osteoblast phenotype over a 21-day culture. Both blends demonstrated improved biocompatibility in a rat subcutaneous implantation model compared to PLAGA over 12 weeks. PMID: 20334909 [PubMed - as supplied by publisher] | | |
| Molecular Regulation of Contractile Smooth Muscle Cell Phenotype: Implications for Vascular Tissue Engineering.
March 26, 2010 at 7:55 AM
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| | Molecular Regulation of Contractile Smooth Muscle Cell Phenotype: Implications for Vascular Tissue Engineering. Tissue Eng Part B Rev. 2010 Mar 24; Authors: Beamish JA, He P, Kottke-Marchant K, Marchant RE The molecular regulation of smooth muscle cell (SMC) behavior is reviewed, with particular emphasis on stimuli that promote the contractile phenotype. SMCs can shift reversibly along a continuum from a quiescent, contractile phenotype to a synthetic phenotype, which is characterized by proliferation and extracellular matrix (ECM) synthesis. This phenotypic plasticity can be harnessed for tissue engineering. Cultured synthetic SMCs have been used to engineer smooth muscle tissues with organized ECM and cell populations. However, returning SMCs to a contractile phenotype remains a key challenge. This review will integrate recent work on how soluble signaling factors, extracellular matrix, mechanical stimulation, and other cells contribute to the regulation of contractile SMC phenotype. The signal transduction pathways and mechanisms of gene expression induced by these stimuli are beginning to be elucidated and provide useful information for the quantitative analysis! of SMC phenotype in engineered tissues. Progress in the development of tissue engineered scaffold systems that implement biochemical, mechanical, or novel polymer fabrication approaches to promote contractile phenotype will also be reviewed. The application of an improved molecular understanding of SMC biology will facilitate the design of more potent cell-instructive scaffold systems to regulate SMC behavior. PMID: 20334504 [PubMed - as supplied by publisher] | | |
| Outcomes of total pelvic exenteration for colorectal cancer.
March 26, 2010 at 7:55 AM
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| | Outcomes of total pelvic exenteration for colorectal cancer. Hepatogastroenterology. 2009 Nov-Dec;56(96):1637-41 Authors: Nishio M, Sakakura C, Nagata T, Miyashita A, Hamada T, Ikoma H, Kubota T, Nakanishi M, Kimura A, Ichikawa D, Kikuchi S, Fujiwara H, Okamoto K, Ochiai T, Kokuba Y, Taniguchi H, Sonoyama T, Hagiwara A, Otsuji E BACKGROUND/AIMS: Pelvic recurrence occurs in 4-33% of patients who have undergone a curative resection of primary rectal cancer and is thus a serious problem. However, the best treatment for primary rectal cancer remains unclear. In the present study was assessed the outcomes of total pelvic exenteration for colorectal cancer retrospectively. METHODOLOGY: In the present study was investigated the medical charts of 25 patients who underwent total pelvic exenteration for primary colorectal cancer (n = 12) or postoperative local recurrence of colorectal cancer (n = 13) at the Department of Surgery (Division of Digestive Surgery) of the Kyoto Prefectural University of Medicine between the years 1997-2005. RESULTS: The mean disease-free time interval between the first operation for primary colorectal cancer and total pelvic exenteration for the recurrence was 919 days (range, 203-3460 days). Total pelvic exenteration required a mean operation time of 940 minutes (range! , 540-1395 minutes). The mean carcinoembryonic antigen (CEA) value was 25.5 ng/ml (range, 1-171.8 ng/ml). Five-year survival was achieved in 9 patients (36%) and inhospital death occurred in 3 patients (12%). The patients with curative resection survived significantly longer than the patients with non-curative resection. CONCLUSIONS: When curative resection is achieved, total pelvic exenteration for colorectal cancer can result in long-term survival. PMID: 20214208 [PubMed - indexed for MEDLINE] | | |
| Student perspectives and opinions on their experience at an undergraduate outreach dental teaching centre at Cardiff: a 5-year study.
March 26, 2010 at 7:55 AM
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| | Student perspectives and opinions on their experience at an undergraduate outreach dental teaching centre at Cardiff: a 5-year study. Eur J Dent Educ. 2010 Feb;14(1):12-6 Authors: Lynch CD, Ash PJ, Chadwick BL AIM: Outreach teaching is now regarded as a desirable component of undergraduate dental teaching programmes in the UK. A purpose-built undergraduate dental outreach-training centre was opened in Cardiff in 2002. The aim of this paper is to report student perspectives and opinions on their experience at this unit over a 5-year period. METHODS: Final year dental students at Cardiff University were invited to report their comments on the St David's Primary Care Unit at various times during their placement there. Information was recorded for undergraduate students who commenced final year in 2003, 2004, 2005, 2006 and 2007 (n = 257). RESULTS: After 1 year, the most common favourable aspects reported by students included the availability of a suitably trained nurse for all procedures (n = 191), ready access to helpful/approachable teaching staff (n = 145), and closeness of learning experience to subsequent practice (n = 122). Many students commented on their growing co! nfidence in their own abilities whilst in the unit. CONCLUSION: Overwhelmingly, students reported their enthusiasm for training in an outreach teaching unit, preferring it to traditional dental school environments. Inherent in the comments recorded for each student was a sense of growing confidence in their abilities and development of reflective practice. Further work is needed to identify the impact of this form of dental student training on subsequent practices in Vocational Training and independent clinical careers. PMID: 20070794 [PubMed - indexed for MEDLINE] | | |
| A Transcriptional Roadmap to the Induction of Pluripotency in Somatic Cells.
March 26, 2010 at 2:55 AM
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| | A Transcriptional Roadmap to the Induction of Pluripotency in Somatic Cells. Stem Cell Rev. 2010 Mar 25; Authors: Wang Y, Mah N, Prigione A, Wolfrum K, Andrade-Navarro MA, Adjaye J Human embryonic stem (ES) cells possess an enormous potential for applications in regenerative medicine. However, these cells have several inevitable hurdles limiting their clinical applications, such as transplant rejection and embryo destruction. A milestone recently achieved was the derivation of induced pluripotent stem (iPS) cells by over-expressing combinations of defined transcription factors, namely, OCT4, SOX2, NANOG, and LIN28 or OCT4, SOX2, KLF4, and c-MYC. Human iPS cells exhibit many characteristics identical to those of inner cell mass-derived ES cells. Here, we summarize the generation of human fibroblast-derived iPS cells and discuss the promises and limitations of their use. In addition, by utilising numerous published transcriptome datasets related to ES cells, fibroblast-derived iPS cells, partially induced pluripotent stem cells (PiPSC) and wild type fibroblasts, we reveal similarities (self-renewal signature) and differences (donor cell-type a! nd PiPSC signatures) in genes and associated signaling pathways operative in the induction of pluripotency in fibroblasts. In particular, we highlight that induction of ground state pluripotency is also favoured by the inhibition of epithelial mesenchymal transition (EMT) and hence the induction of mesenchymal epithelial transition (MET). We anticipate that these findings might aid in the establishment of more efficient protocols for inducing pluripotency in somatic cells. PMID: 20336394 [PubMed - as supplied by publisher] | | |
| A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates.
March 26, 2010 at 2:55 AM
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| | A purified population of multipotent cardiovascular progenitors derived from primate pluripotent stem cells engrafts in postmyocardial infarcted nonhuman primates. J Clin Invest. 2010 Mar 24; Authors: Blin G, Nury D, Stefanovic S, Neri T, Guillevic O, Brinon B, Bellamy V, Rücker-Martin C, Barbry P, Bel A, Bruneval P, Cowan C, Pouly J, Mitalipov S, Gouadon E, Binder P, Hagège A, Desnos M, Renaud JF, Menasché P, Pucéat M Cell therapy holds promise for tissue regeneration, including in individuals with advanced heart failure. However, treatment of heart disease with bone marrow cells and skeletal muscle progenitors has had only marginal positive benefits in clinical trials, perhaps because adult stem cells have limited plasticity. The identification, among human pluripotent stem cells, of early cardiovascular cell progenitors required for the development of the first cardiac lineage would shed light on human cardiogenesis and might pave the way for cell therapy for cardiac degenerative diseases. Here, we report the isolation of an early population of cardiovascular progenitors, characterized by expression of OCT4, stage-specific embryonic antigen 1 (SSEA-1), and mesoderm posterior 1 (MESP1), derived from human pluripotent stem cells treated with the cardiogenic morphogen BMP2. This progenitor population was multipotential and able to generate cardiomyocytes as well as smooth muscle! and endothelial cells. When transplanted into the infarcted myocardium of immunosuppressed nonhuman primates, an SSEA-1+ progenitor population derived from Rhesus embryonic stem cells differentiated into ventricular myocytes and reconstituted 20% of the scar tissue. Notably, primates transplanted with an unpurified population of cardiac-committed cells, which included SSEA-1- cells, developed teratomas in the scar tissue, whereas those transplanted with purified SSEA-1+ cells did not. We therefore believe that the SSEA-1+ progenitors that we have described here have the potential to be used in cardiac regenerative medicine. PMID: 20335662 [PubMed - as supplied by publisher] | | | | 
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