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| Former Novocell/JDRF Chief Hooking Up With CIRM
June 29, 2010 at 12:53 PM
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| Alan Lewis, the fomer head of Novocell (now ViaCyte, Inc.) and the Juvenile Diabetes Research Foundation, will be joining the $3 billion California stem cell agency shortly, the California Stem Cell Report has learned.
It is not clear what his responsibilities will include or whether he will be serving as a consultant or on staff. The agency has been seeking a vice president for research and | | |
| Prospects for stem cell transplantation in the treatment of hepatic disease.
June 29, 2010 at 7:51 AM
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| | Prospects for stem cell transplantation in the treatment of hepatic disease. Liver Transpl. 2010 Apr 14;16(7):827-836 Authors: Stutchfield BM, Forbes SJ, Wigmore SJ Stem cell therapy has the potential to provide a valuable adjunct to the management of hepatic disease. Preclinical studies have demonstrated a range of endogenous repair processes that can be exploited through stem cell therapy. Initial translational studies have been encouraging and have suggested improved liver function in advanced chronic liver disease and enhanced liver regeneration after portal vein embolization. This article reviews the potential for stem cell therapies to enhance hepatic regeneration in acute and chronic hepatic disease and is based on a MEDLINE and PubMed search for English language articles investigating mechanisms of hepatic regeneration and delivery of cell therapies. Two main mechanisms of potential stem cell therapy delivery have emerged: (1) a direct contribution to the functional hepatocyte population with embryonic, induced pluripotent, or adult stem cells and (2) the promotion of endogenous regenerative processes with bone marrow-derived stem cells. Bioartificial hepatic support systems may be proven to be an effective method of using ex vivo differentiated hepatocytes and be indicated as a bridging therapy to definitive surgery in acute liver failure. The administration of bone marrow-derived stem cells may enhance liver regeneration in chronic liver disease after portal vein embolization and could facilitate regeneration after partial hepatic resection. Ultimately, the most appropriate hepatic disease targets for stem cell therapies will become apparent as mechanisms of stem involvement in hepatic regeneration are further elucidated. Liver Transpl 16:827-836, 2010. (c) 2010 AASLD. PMID: 20583084 [PubMed - as supplied by publisher] | | |
| Synthesis and characterization of a Hyaluronan-polyethylene copolymer for biomedical applications.
June 29, 2010 at 6:37 AM
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| | Synthesis and characterization of a Hyaluronan-polyethylene copolymer for biomedical applications. J Biomed Mater Res B Appl Biomater. 2010 Jun 25; Authors: Oldinski RA, Cranson CN, James SP Hyaluronan (HA)-based biomaterials are of interest for bone and cartilage tissue engineering because HA plays an important role in orthopedic tissue development, function, and repair. The goal of this project was to develop a biomaterial that incorporated the constituents of both a hydrogel and a hydrophobic polymer for biomedical applications. A series of amphiphilic graft copolymers consisting of HA, a glycosaminoglycan, and high-density polyethylene (HDPE), that is, HA-co-HDPE, were fabricated. The chemical characteristics, physical and viscoelastic properties, and cytocompatibility of novel HA-co-HDPE materials were characterized via Fourier Transform infrared (FTIR) spectroscopy, solid state nuclear magnetic resonance (ssNMR) spectroscopy, differential scanning calorimetry (DSC), dynamic shear testing, and an in vitro human osteoblast cell study. The esterification reaction between HA and functionalized HDPE resulted in semicrystalline, insoluble powder. The dynamic shear properties of HA-co-HDPE concentrated solutions were more like natural proteoglycans than the HA control. HA-co-HDPE was successfully compression molded into disks that swelled upon hydration. Osteoblasts were viable and expressed the osteoblast phenotype after 7 days of culture on HA-co-HDPE materials. These HA-co-HDPE materials may have several biomaterial applications in saline suspension or molded form, including orthopedic tissue repair. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20583303 [PubMed - as supplied by publisher] | | |
| Cytochrome c Oxidase is Essential for Copper-Induced Regression of Cardiomyocyte Hypertrophy.
June 29, 2010 at 6:37 AM
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| | Cytochrome c Oxidase is Essential for Copper-Induced Regression of Cardiomyocyte Hypertrophy. Cardiovasc Toxicol. 2010 Jun 26; Authors: Zuo X, Xie H, Dong D, Jiang N, Zhu H, Kang YJ Previous studies have shown that both copper (Cu) and vascular endothelial growth factor (VEGF) reduce the size of hypertrophic cardiomyocytes, but the Cu-induced regression is VEGF dependent. Studies in vivo have shown that hypertrophic cardiomyopathy is associated with a depression in cytochrome c oxidase (COX) activity, which could be involved in VEGF-mediated cellular function. The present study was undertaken to test the hypothesis that COX is a determinant factor in Cu-induced regression of cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were treated with phenylepherine (PE) at a final concentration of l00 muM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cells were then treated with Cu sulfate at a final concentration of 5 muM in cultures for 24 h with a concomitant presence of PE to examine the effect of Cu on the regression of cardiomyocyte hypertrophy. Cell size changes were determined by flow cytometry, protein content, and molecular markers. Gene silencing was applied to study the effect of COX activity change on the regression of cardiomyocyte hypertrophy. PE treatment decreased COX activity in hypertrophic cardiomyocytes, and Cu addition restored the activity along with the regression of cell hypertrophy. Gene silencing using siRNA targeting COX-I significantly inhibited COX activity and blocked the Cu-induced regression of cell hypertrophy. VEGF alone also restored COX activity; but under the condition of COX inhibition by gene silencing, VEGF-induced regression of cell hypertrophy was suppressed. This study demonstrates that both Cu and VEGF can restore COX activity that is depressed in hypertrophic cardiomyocytes, and COX plays a determinant role in both Cu- and VEGF-induced regression of cardiomyocyte hypertrophy. PMID: 20582486 [PubMed - as supplied by publisher] | | |
| Polymer nanofibrous structures: Fabrication, biofunctionalization, and cell interactions.
June 29, 2010 at 6:37 AM
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| | Polymer nanofibrous structures: Fabrication, biofunctionalization, and cell interactions. Prog Polym Sci. 2010 Jul 1;35(7):868-892 Authors: Beachley V, Wen X Extracellular matrix fibers (ECM) such as collagen, elastin, and keratin provide biological and physical support for cell attachment, proliferation, migration, differentiation and ultimately cell fate. Therefore, ECM fibers are an important component in tissue and organ development and regeneration. Meanwhile, polymer nanofibers could play the same critical role in tissue regeneration process. Fibrous structures can be fabricated from a variety of materials and methods with diameters ranging throughout the size scale where cells can sense individual fibers (several nanometers to several microns). Polymer nanofiber scaffolds can be designed in a way that predictably modulates a variety of important cell behaviors towards a desired overall function. The nanofibrous topography itself, independent of the fiber material, has demonstrated the potential to modulate cell behaviors desirable in tissue engineering such as: unidirectional alignment; increased viability, attachment, and ECM production; guided migration; and controlled differentiation. The versatility of polymer nanofibers for functionalization with biomolecules opens the door to vast opportunities for the design of tissue engineering scaffolds with even greater control over cell incorporation and function. Despite the promise of polymer nanofibers as tissue engineering scaffolds there have been few clinically relevant successes because no single fabrication technique currently combines control over structural arrangement, material composition, and biofunctionalization, while maintaining reasonable cost and yield. Promising strategies are currently being investigated to allow for the fabrication of optimal polymer nanofiber tissue engineering scaffolds with the goal of treating damaged and degenerated tissues in a clinical setting. PMID: 20582161 [PubMed - as supplied by publisher] | | |
| The effect of type II collagen coating of chitosan fibrous scaffolds on mesenchymal stem cell adhesion and chondrogenesis.
June 29, 2010 at 6:37 AM
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| | The effect of type II collagen coating of chitosan fibrous scaffolds on mesenchymal stem cell adhesion and chondrogenesis. Acta Biomater. 2010 May 22; Authors: Ragetly GR, Griffon DJ, Chung YS The biocompatibility of chitosan and its similarity with glycosaminoglycans (GAG) make it attractive for cartilage tissue engineering. We have previously reported improved chondrogenesis but limited cell adhesion on chitosan scaffolds. Our objectives were to produce chitosan scaffolds coated with different densities of type II collagen and to evaluate the effect of this coating on mesenchymal stem cells (MSCs) adhesion and chondrogenesis. Chitosan fibrous scaffolds were obtained by a wet spinning method and coated with type II collagen at two different densities. A polyglycolic acid mesh served as a reference group. The scaffolds were characterized by Fourier-transform infrared spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and type II collagen content. Constructs were analyzed after MSCs seeding via live/dead assay, weight and DNA evaluations, SEM, and TEM. Constructs were cultured in chondrogenic medium for 21 days prior to quantitative analysis (weight, DNA, and GAG), SEM, TEM, histology, immunohistochemistry, and quantitative real time polymerase chain reaction. The cell attachment and distribution after seeding correlated with the density of type II collagen. The cell number, the matrix production, and the expression of genes specific for chondrogenesis were improved after culture in collagen coated chitosan constructs. These findings encourage the use of type II collagen for coating chitosan scaffolds to improve MSCs adhesion and chondrogenesis, and confirm the importance of biomimetic scaffolds for tissue engineering. PMID: 20580951 [PubMed - as supplied by publisher] | | |
| Human corneal epithelial cell response to epidermal growth factor tethered via coiled-coil interactions.
June 29, 2010 at 6:37 AM
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| | Human corneal epithelial cell response to epidermal growth factor tethered via coiled-coil interactions. Biomaterials. 2010 Jun 23; Authors: Boucher C, Ruiz JC, Thibault M, Buschmann MD, Wertheimer MR, Jolicoeur M, Durocher Y, De Crescenzo G The development of new strategies for protein immobilization to control cell adhesion, growth and differentiation is of prime interest in the field of tissue engineering. Here we propose a versatile approach based on the interaction between two de novo designed peptides, Ecoil and Kcoil, for oriented immobilization of epidermal growth factor (EGF) on polyethylene terephthalate (PET) films. After amination of PET surfaces by ammonia plasma treatment, Kcoil peptides were covalently grafted in an oriented fashion using succinimidyl 6-[30-(2-pyridyldithio)-propionamido] hexanoate (LC-SPDP) linker, and the Kcoil-functionalized films were characterized by X-ray photoelectron spectroscopy (XPS). Bioactivity of Ecoil-EGF captured on Kcoil-functionalized PET via coiled-coil interactions was confirmed by EGF receptor phosphorylation analysis following A-431 cell attachment. We also demonstrated cell biological effects where tethered EGF enhanced adhesion, spreading and proliferation of human corneal epithelial cells compared to EGF that was either physically adsorbed or present in solution. Tethered EGF effects were most likely linked to the prolonged activation of both mitogen-activated protein kinase and phosphoinositidine 3-kinase pathways. Taken together, our results indicate that coiled-coil-based oriented immobilization is a powerful method to specifically tailor biomaterial surfaces for tissue engineering applications. PMID: 20579729 [PubMed - as supplied by publisher] | | |
| Influence of micro-patterned PLLA membranes on outgrowth and orientation of hippocampal neurites.
June 29, 2010 at 6:37 AM
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| | Influence of micro-patterned PLLA membranes on outgrowth and orientation of hippocampal neurites. Biomaterials. 2010 Jun 23; Authors: Morelli S, Salerno S, Piscioneri A, Papenburg BJ, Di Vito A, Giusi G, Canonaco M, Stamatialis D, Drioli E, De Bartolo L In neuronal tissue engineering many efforts are focused on creating biomaterials with physical and chemical pathways for controlling cellular proliferation and orientation. Neurons have the ability to respond to topographical features in their microenvironment causing among others, axons to proliferate along surface features such as substrate grooves in micro-and nanoscales. As a consequence these neuronal elements are able to correctly adhere, migrate and orient within their new environment during growth. Here we explored the polarization and orientation of hippocampal neuronal cells on nonpatterned and micro-patterned biodegradable poly(l-lactic acid) (PLLA) membranes with highly selective permeable properties. Dense and porous nonpatterned and micro-patterned membranes were prepared from PLLA by Phase Separation Micromolding. The micro-patterned membranes have a three-dimensional structure consisting of channels and ridges and of bricks of different widths. Nonpatterned and patterned membranes were used for hippocampal neuronal cultures isolated from postnatal days 1-3 hamsters and the neurite length, orientation and specific functions of cells were investigated up to 12 days of culture. Neurite outgrowth, length plus orientation tightly overlapped the pattern of the membrane surface. Cell distribution occurred only in correspondence to membrane grooves characterized by continuous channels whereas on membranes with interconnected channels, cells not only adhered to and elongated their cellular processes in the grooves but also in the breaking points. High orientation degrees of cells were determined particularly on the patterned porous membranes with channel width of 20 mum and ridges of 17 mum whereas on dense nonpatterned membranes as well as on polystyrene culture dish (PSCD) controls, a larger number of primary developed neurites were distributed. Based on these results, PLLA patterned membranes may directly improve the guidance of neurite extension and thereby enhancing their orientation with a consequently highly ordered neuronal cell matrix, which may have strong bearings on the elucidation of regeneration mechanisms. PMID: 20579728 [PubMed - as supplied by publisher] | | |
| Mathematically defined tissue engineering scaffold architectures prepared by stereolithography.
June 29, 2010 at 6:37 AM
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| | Mathematically defined tissue engineering scaffold architectures prepared by stereolithography. Biomaterials. 2010 Jun 23; Authors: Melchels FP, Bertoldi K, Gabbrielli R, Velders AH, Feijen J, Grijpma DW The technologies employed for the preparation of conventional tissue engineering scaffolds restrict the materials choice and the extent to which the architecture can be designed. Here we show the versatility of stereolithography with respect to materials and freedom of design. Porous scaffolds are designed with computer software and built with either a poly(d,l-lactide)-based resin or a poly(d,l-lactide-co-epsilon-caprolactone)-based resin. Characterisation of the scaffolds by micro-computed tomography shows excellent reproduction of the designs. The mechanical properties are evaluated in compression, and show good agreement with finite element predictions. The mechanical properties of scaffolds can be controlled by the combination of material and scaffold pore architecture. The presented technology and materials enable an accurate preparation of tissue engineering scaffolds with a large freedom of design, and properties ranging from rigid and strong to highly flexible and elastic. PMID: 20579724 [PubMed - as supplied by publisher] | | |
| Hunter-Schreger Band patterns in human tooth enamel.
June 29, 2010 at 6:37 AM
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| | Hunter-Schreger Band patterns in human tooth enamel. J Anat. 2010 Jun 23; Authors: Lynch CD, O'Sullivan VR, Dockery P, McGillycuddy CT, Sloan AJ Abstract Using light microscopy, we examined Hunter-Schreger Band (HSB) patterns on the axial and occlusal/incisal surfaces of 160 human teeth, sectioned in both the buccolingual and mesiodistal planes. We found regional variations in HSB packing densities (number of HSBs per mm of amelodentinal junction length) and patterns throughout the crown of each class of tooth (maxillary and mandibular: incisor, canine, premolar, and molar) examined. HSB packing densities were greatest in areas where functional and occlusal loads are greatest, such as the occlusal surfaces of posterior teeth and the incisal regions of incisors and canines. From this it is possible to infer that the behaviour of ameloblasts forming enamel prisms during amelogenesis is guided by genetic/evolutionary controls that act to increase the fracture and wear resistance of human tooth enamel. It is suggested that HSB packing densities and patterns are important in modern clinical dental treatments, such as the bonding of adhesive restorations to enamel, and in the development of conditions, such as abfraction and cracked tooth syndrome. PMID: 20579171 [PubMed - as supplied by publisher] | | |
| Fibrin-polylactide-based tissue-engineered vascular graft in the arterial circulation.
June 29, 2010 at 6:37 AM
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| | Fibrin-polylactide-based tissue-engineered vascular graft in the arterial circulation. Biomaterials. 2010 Jun;31(17):4731-9 Authors: Koch S, Flanagan TC, Sachweh JS, Tanios F, Schnoering H, Deichmann T, Ellä V, Kellomäki M, Gronloh N, Gries T, Tolba R, Schmitz-Rode T, Jockenhoevel S There is a clear clinical requirement for the design and development of living, functional, small-calibre arterial grafts. Here, we investigate the potential use of a small diameter, tissue-engineered artery in a pre-clinical study in the carotid artery position of sheep. Small-calibre ( approximately 5 mm) vascular composite grafts were molded using a fibrin scaffold supported by a poly(L/D)lactide 96/4 (P(L/D)LA 96/4) mesh, and seeded with autologous arterial-derived cells prior to 28 days of dynamic conditioning. Conditioned grafts were subsequently implanted for up to 6 months as interposed carotid artery grafts in the same animals from which the cells were harvested. Explanted grafts (n = 6) were patent in each of the study groups (1 month, 3 months, 6 months), with a significant stenosis in one explant (3 months). There was a complete absence of thrombus formation on the luminal surface of grafts, with no evidence for aneurysm formation or calcification after 6 months in vivo. Histological analyses revealed remodeling of the fibrin scaffold with mature autologous proteins, and excellent cell distribution within the graft wall. Positive vWf and eNOS staining, in addition to scanning electron microscopy, revealed a confluent monolayer of endothelial cells lining the luminal surface of the grafts. The present study demonstrates the successful production and mid-term application of an autologous, fibrin-based small-calibre vascular graft in the arterial circulation, and highlights the potential for the creation of autologous implantable arterial grafts in a number of settings. PMID: 20304484 [PubMed - indexed for MEDLINE] | | |
| Repair of a segmental long bone defect in human by implantation of a novel multiple disc graft.
June 29, 2010 at 6:37 AM
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| | Repair of a segmental long bone defect in human by implantation of a novel multiple disc graft. Bone. 2010 May;46(5):1457-63 Authors: Hesse E, Kluge G, Atfi A, Correa D, Haasper C, Berding G, Shin HO, Viering J, Länger F, Vogt PM, Krettek C, Jagodzinski M Large segmental defects of the weight bearing long bones are very difficult to reconstruct. Current treatment options are afflicted with several limitations and disadvantages. We describe a novel approach to regenerate a segmental long bone defect in a patient using a multiple disc graft. Decellularized bovine trabecular bone discs were seeded with autologous bone marrow cells and cultured in a perfusion chamber for three weeks. Multiple cell-seeded discs were implanted to close a 72 mm defect of the distal tibia in a 58-year-old woman, and fixed by an intramedullary nail. Bone formation was assessed non-invasively by plain radiographs and 18F-labeled sodium fluoride-based co-registration of positron emission- and computed tomography (PET/CT). Bone was actively formed around the grafted defect as early as six weeks after surgery. Because the tibia was sufficiently stabilized, the patient was able to freely walk with full weight bearing 6 weeks after surgery. The uneventful two-year follow-up and the satisfaction of the patient demonstrated the success of the procedure. Therefore the use of multiple cell-seeded disc grafts can be considered as a treatment alternative for patients with segmental long bone defects. PMID: 20153850 [PubMed - indexed for MEDLINE] | | |
| Prospects for stem cell transplantation in the treatment of hepatic disease.
June 29, 2010 at 6:10 AM
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| | Prospects for stem cell transplantation in the treatment of hepatic disease. Liver Transpl. 2010 Apr 14;16(7):827-836 Authors: Stutchfield BM, Forbes SJ, Wigmore SJ Stem cell therapy has the potential to provide a valuable adjunct to the management of hepatic disease. Preclinical studies have demonstrated a range of endogenous repair processes that can be exploited through stem cell therapy. Initial translational studies have been encouraging and have suggested improved liver function in advanced chronic liver disease and enhanced liver regeneration after portal vein embolization. This article reviews the potential for stem cell therapies to enhance hepatic regeneration in acute and chronic hepatic disease and is based on a MEDLINE and PubMed search for English language articles investigating mechanisms of hepatic regeneration and delivery of cell therapies. Two main mechanisms of potential stem cell therapy delivery have emerged: (1) a direct contribution to the functional hepatocyte population with embryonic, induced pluripotent, or adult stem cells and (2) the promotion of endogenous regenerative processes with bone marrow-derived stem cells. Bioartificial hepatic support systems may be proven to be an effective method of using ex vivo differentiated hepatocytes and be indicated as a bridging therapy to definitive surgery in acute liver failure. The administration of bone marrow-derived stem cells may enhance liver regeneration in chronic liver disease after portal vein embolization and could facilitate regeneration after partial hepatic resection. Ultimately, the most appropriate hepatic disease targets for stem cell therapies will become apparent as mechanisms of stem involvement in hepatic regeneration are further elucidated. Liver Transpl 16:827-836, 2010. (c) 2010 AASLD. PMID: 20583084 [PubMed - as supplied by publisher] | | |
| Cytochrome c Oxidase is Essential for Copper-Induced Regression of Cardiomyocyte Hypertrophy.
June 29, 2010 at 6:10 AM
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| | Cytochrome c Oxidase is Essential for Copper-Induced Regression of Cardiomyocyte Hypertrophy. Cardiovasc Toxicol. 2010 Jun 26; Authors: Zuo X, Xie H, Dong D, Jiang N, Zhu H, Kang YJ Previous studies have shown that both copper (Cu) and vascular endothelial growth factor (VEGF) reduce the size of hypertrophic cardiomyocytes, but the Cu-induced regression is VEGF dependent. Studies in vivo have shown that hypertrophic cardiomyopathy is associated with a depression in cytochrome c oxidase (COX) activity, which could be involved in VEGF-mediated cellular function. The present study was undertaken to test the hypothesis that COX is a determinant factor in Cu-induced regression of cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were treated with phenylepherine (PE) at a final concentration of l00 muM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cells were then treated with Cu sulfate at a final concentration of 5 muM in cultures for 24 h with a concomitant presence of PE to examine the effect of Cu on the regression of cardiomyocyte hypertrophy. Cell size changes were determined by flow cytometry, protein content, and molecular markers. Gene silencing was applied to study the effect of COX activity change on the regression of cardiomyocyte hypertrophy. PE treatment decreased COX activity in hypertrophic cardiomyocytes, and Cu addition restored the activity along with the regression of cell hypertrophy. Gene silencing using siRNA targeting COX-I significantly inhibited COX activity and blocked the Cu-induced regression of cell hypertrophy. VEGF alone also restored COX activity; but under the condition of COX inhibition by gene silencing, VEGF-induced regression of cell hypertrophy was suppressed. This study demonstrates that both Cu and VEGF can restore COX activity that is depressed in hypertrophic cardiomyocytes, and COX plays a determinant role in both Cu- and VEGF-induced regression of cardiomyocyte hypertrophy. PMID: 20582486 [PubMed - as supplied by publisher] | | |
| A novel Gfer-Drp1 link in preserving mitochondrial dynamics and function in pluripotent stem cells.
June 29, 2010 at 6:10 AM
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| | A novel Gfer-Drp1 link in preserving mitochondrial dynamics and function in pluripotent stem cells. Autophagy. 2010 Aug 9;6(6) Authors: Todd LR, Gomathinayagam R, Sankar U Mitochondria, the dynamic energy powerhouses of the cell, have vital roles in a multitude of cellular processes including differentiation and cell survival. Tight regulation of mitochondrial dynamics, integrity and function is indispensible for preservation of homeostasis in all cells, including pluripotent stem cells. The ability to proliferate and self-renew indefinitely bestows the pluripotent embryonic stem cells (ESCs) with immense curative potential. Mechanisms that preserve mitochondrial well-being, and therefore maintain "stemness," are vital in realizing the full potential of ESCs in therapeutic regenerative medicine. However, virtually nothing is known regarding the regulation of mitochondrial dynamics and function and the relationship thereof to overall cell fate and function in pluripotent ESCs or other somatic stem cells. Using loss- and gain-of-function approaches, we show that growth factor erv1-like (Gfer) plays an essential pro-survival role in the maintenance of murine ESC pluripotency by preserving the structural and functional integrity of their mitochondria, through modulation of the key mitochondrial fission factor Drp1. PMID: 20581476 [PubMed - as supplied by publisher] | | |
| Muscle stem cells and reversible quiescence: The role of sprouty.
June 29, 2010 at 6:10 AM
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| | Muscle stem cells and reversible quiescence: The role of sprouty. Cell Cycle. 2010 Jul 26;9(13) Authors: Abou-Khalil R, Brack AS Quiescence is a critical determinant for sustained stem cell function throughout life. Disruption of cellular quiescence leads to loss of the stem cell pool and impaired tissue repair. In adult skeletal muscle, Pax7(+) satellite cells (the muscle stem cells) are capable of self-renewal and differentiation in their endogenous environment during repair. In response to muscle injury, Pax7(+) satellite cells enter the cell cycle; a subpopulation returns to quiescence to fully replenish the satellite cell pool while others contribute to myofiber repair. We demonstrate that Sprouty1 (Spry1), an inhibitor of receptor tyrosine kinase signaling is required for the return to quiescence of the self-renewing Pax7(+) satellite cell pool during repair. The temporal regulation of Spry1 expression during repair and its functional requirement in a subpopulation of cycling Pax7(+) cells during repair ensure that tissue regeneration and re-establishment of the dormant stem cell pool are coordinated. PMID: 20581433 [PubMed - as supplied by publisher] | | |
| Hot Topics in Stem Cells and Self-Renewal: 2010.
June 29, 2010 at 6:10 AM
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| | Hot Topics in Stem Cells and Self-Renewal: 2010. Aging Cell. 2010 Jun 24; Authors: Sharpless NE Abstract In many tissues, mammalian aging is associated with a decline in the replicative and functional capacity of somatic stem cells and other self-renewing compartments. Understanding the basis of this decline is a major goal of aging research. In particular, therapeutic approaches to ameliorate or reverse the age-associated loss of stem function could be of use in clinical geriatrics. Such approaches include attempts to protect stem cells from age-promoting damage, to 'rejuvenate' stem cells through the use of pharmacologic agents that mitigate aging-induced alterations in signaling, and to replace lost stem cells through regenerative medicine approaches. Some headway has been made in each of these arenas over the last 18 months including advances in the production of donor-specific totipotent stem cells through induced pluripotency (iPS), gains in our understanding of how tumor suppressor signaling is controlled in self-renewing compartments to regulate aging, and further demonstration of extracellular 'milieu' factors that perturb stem cell function with age. This period has also been marked by the recent award of the Nobel Prize in Physiology or Medicine for elucidation of telomeres and telomerase, a topic of critical importance to stem cell aging. PMID: 20579010 [PubMed - as supplied by publisher] | | |
| Attenuation of the hypoxia-induced protein kinase Cdelta interaction with the 'd' subunit of F1Fo-ATP synthase in neonatal cardiac myocytes: implications for energy preservation and survival.
June 29, 2010 at 6:10 AM
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| | Attenuation of the hypoxia-induced protein kinase Cdelta interaction with the 'd' subunit of F1Fo-ATP synthase in neonatal cardiac myocytes: implications for energy preservation and survival. Biochem J. 2010 Jun 28;429(2):335-45 Authors: Nguyen TT, Ogbi M, Yu Q, Johnson JA The F1Fo-ATP synthase provides most of the heart's energy, yet events that alter its function during injury are poorly understood. Recently, we described a potent inhibitory effect on F1Fo-ATP synthase function mediated by the interaction of PKCdelta (protein kinase Cdelta) with dF1Fo ('d' subunit of the F1Fo-ATPase/ATP synthase). We have now developed novel peptide modulators which facilitate or inhibit the PKCdelta-dF1Fo interaction. These peptides include HIV-Tat (transactivator of transcription) protein transduction and mammalian mitochondrial-targeting sequences. Pre-incubation of NCMs (neonatal cardiac myocyte) with 10 nM extracellular concentrations of the mitochondrial-targeted PKCdelta-dF1Fo interaction inhibitor decreased Hx (hypoxia)-induced co-IP (co-immunoprecipitation) of PKCdelta with dF1Fo by 40+/-9%, abolished Hx-induced inhibition of F1Fo-ATPase activity, attenuated Hx-induced losses in F1Fo-derived ATP and protected against Hx- and reperfusion-induced cell death. A scrambled-sequence (inactive) peptide, which contained HIV-Tat and mitochondrial-targeting sequences, was without effect. In contrast, the cell-permeant mitochondrial-targeted PKCdelta-dF1Fo facilitator peptide, which we have shown previously to induce the PKCdelta-dF1Fo co-IP, was found to inhibit F1Fo-ATPase activity to an extent similar to that caused by Hx alone. The PKCdelta-dF1Fo facilitator peptide also decreased ATP levels by 72+/-18% under hypoxic conditions in the presence of glycolytic inhibition. None of the PKCdelta-dF1Fo modulatory peptides altered the inner mitochondrial membrane potential. Our studies provide the first evidence that disruption of the PKCdelta-dF1Fo interaction using cell-permeant mitochondrial-targeted peptides attenuates cardiac injury resulting from prolonged oxygen deprivation. PMID: 20578995 [PubMed - in process] | | |
| Bone-Targeted Doxorubicin-Loaded Nanoparticles as a Tool for the Treatment of Skeletal Metastases.
June 29, 2010 at 6:10 AM
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| | Bone-Targeted Doxorubicin-Loaded Nanoparticles as a Tool for the Treatment of Skeletal Metastases. Curr Cancer Drug Targets. 2010 Jun 25; Authors: Salerno M, Cenni E, Fotia C, Avnet S, Granchi D, Castelli F, Micieli D, Pignatello R, Capulli M, Rucci N, Angelucci A, Del Fattore A, Teti A, Zini N, Giunti A, Baldini N Bone metastases contribute to morbidity in patients with common cancers, and conventional therapy provides only palliation and can induce systemic side effects. The development of nanostructured delivery systems that combine carriers with bone-targeting molecules can potentially overcome the drawbacks presented by conventional approaches. We have recently developed biodegradable, biocompatible nanoparticles (NP) made of a conjugate between poly (D,L-lactide-co-glycolic) acid and alendronate, suitable for systemic administration, and directly targeting the site of tumor-induced osteolysis. Here, we loaded NP with doxorubicin (DXR), and analyzed the in vitro and in vivo activity of the drug encapsulated in the carrier system. After confirming the intracellular uptake of DXR-loaded NP, we evaluated the anti-tumor effects in a panel of human cell lines, representative for primary or metastatic bone tumors, and in an orthotopic mouse model of breast cancer bone metastases. In vitro, both free DXR and DXR-loaded NP, (58-580 ng/mL) determined a significant dose-dependent growth inhibition of all cell lines. Similarly, both DXR-loaded NP and free DXR reduced the incidence of metastases in mice. Unloaded NP were ineffective, although both DXR-loaded and unloaded NP significantly reduced the osteoclast number at the tumor site (P = 0.014, P = 0.040, respectively), possibly as a consequence of alendronate activity. In summary, NP may act effectively as a delivery system of anticancer drugs to the bone, and deserve further evaluation for the treatment of bone tumors. PMID: 20578992 [PubMed - as supplied by publisher] | | |
| Repair of a segmental long bone defect in human by implantation of a novel multiple disc graft.
June 29, 2010 at 6:10 AM
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| | Repair of a segmental long bone defect in human by implantation of a novel multiple disc graft. Bone. 2010 May;46(5):1457-63 Authors: Hesse E, Kluge G, Atfi A, Correa D, Haasper C, Berding G, Shin HO, Viering J, Länger F, Vogt PM, Krettek C, Jagodzinski M Large segmental defects of the weight bearing long bones are very difficult to reconstruct. Current treatment options are afflicted with several limitations and disadvantages. We describe a novel approach to regenerate a segmental long bone defect in a patient using a multiple disc graft. Decellularized bovine trabecular bone discs were seeded with autologous bone marrow cells and cultured in a perfusion chamber for three weeks. Multiple cell-seeded discs were implanted to close a 72 mm defect of the distal tibia in a 58-year-old woman, and fixed by an intramedullary nail. Bone formation was assessed non-invasively by plain radiographs and 18F-labeled sodium fluoride-based co-registration of positron emission- and computed tomography (PET/CT). Bone was actively formed around the grafted defect as early as six weeks after surgery. Because the tibia was sufficiently stabilized, the patient was able to freely walk with full weight bearing 6 weeks after surgery. The uneventful two-year follow-up and the satisfaction of the patient demonstrated the success of the procedure. Therefore the use of multiple cell-seeded disc grafts can be considered as a treatment alternative for patients with segmental long bone defects. PMID: 20153850 [PubMed - indexed for MEDLINE] | | | | 
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A firm founded by a part-time, but award-winning poet was the only company to receive a grant in last week's round from the $3 billion California stem cell agency. The firm is Escape Therapeutics of Palo Alto, Ca. The principal investigator on the $1.5 million CIRM grant is Basil Hantash(see photo), founder of the firm and an Illinois native who held a biodesign fellowship in 2006-07 at
