| Potential role of tartrate-resistant acid phosphatase 5b (TRACP 5b) as a surrogate marker of late loosening in patients with total hip arthroplasty: A cohort study.
January 12, 2010 at 9:08 AM
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| | Potential role of tartrate-resistant acid phosphatase 5b (TRACP 5b) as a surrogate marker of late loosening in patients with total hip arthroplasty: A cohort study. J Orthop Res. 2010 Jan 8; Authors: Savarino L, Avnet S, Greco M, Giunti A, Baldini N In a cohort study, the role of the active tartrate-resistant acid phosphatase (TRACP 5b), a marker of bone-resorbing osteoclasts, for the assessment of loosening after total hip arthroplasty (THA), was analyzed, as well as its correlation with osteolysis and multinucleated cell appearance in the retrievals. Eighty THA patients, who went consecutively to the orthopedic department, were asked to participate, and 54 accepted and were enrolled in the study. Finally, 46 subjects were analyzed, clinical-radiographic evaluation was considered the gold standard, serum TRACP 5b was blindly measured, and a cut-off was obtained, by performing a ROC Curve. Based on the gold standard, patients were split by 19 stable and 27 loosened subjects, and results were matched. TRACP 5b was significantly higher in loosened patients than in stable ones (p < 0.001). A good specificity (89.5%), positive predictive value (90.0%), and likelihood ratio (6.33) were calculated, that provided! strong evidence of loosening with TRACP 5b levels higher than the cut-off. Moreover, TRACP 5b and osteolysis (Fisher's exact test, p = 0.03) were found significantly correlated. TRACP 5b has been proven a reliable marker, specifically related to resorbing-multinucleated cells, to ascertain late loosening in THA, and could support standard procedures, if confirmed by performing prospective studies. (c) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. PMID: 20063383 [PubMed - as supplied by publisher] | | |
| Effects of Altered Bone Remodeling and Retention of Cement Lines on Bone Quality in Osteopetrotic Aged c-Src-Deficient Mice.
January 12, 2010 at 9:08 AM
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| | Effects of Altered Bone Remodeling and Retention of Cement Lines on Bone Quality in Osteopetrotic Aged c-Src-Deficient Mice. Calcif Tissue Int. 2010 Jan 9; Authors: Nakayama H, Takakuda K, Matsumoto HN, Miyata A, Baba O, Tabata MJ, Ushiki T, Oda T, McKee MD, Takano Y Cement lines represent mineralized, extracellular matrix interfacial boundaries at which bone resorption by osteoclasts is followed by bone deposition by osteoblasts. To determine the contribution of cement lines to bone quality, the osteopetrotic c-Src mouse model-where cement lines accumulate and persist as a result of defective osteoclastic resorption-was used to investigate age-related changes in structural and mechanical properties of bone having long-lasting cement lines. Cement lines of osteopetrotic bones in c-Src knockout mice progressively mineralized with age up to the level that the entire matrix of cement lines was lost by EDTA decalcification. While it was anticipated that suppressed and abnormal remodeling, together with the accumulation of cement line interfaces, would lead to defective bone quality with advancing age of the mutant mice, unexpectedly, three-point bending tests of the long bones of 1-year-old c-Src-deficient mice indicated significa! ntly elevated strength relative to age-matched wild-type bones despite the presence of numerous de novo microcracks. Among these microcracks in the c-Src bones, there was no sign of preferential propagation or arrest of microcracks along the cement lines in either fractured or nonfractured bones of old c-Src mice. These data indicate that cement lines are not the site of a potential internal failure of bone strength in aged c-Src osteopetrotic mice and that abundant and long-lasting cement lines in these osteopetrotic bones appear to have no negative impacts on the mechanical properties of this low-turnover bone despite their progressive hypermineralization (and thus potential brittleness) with age. PMID: 20063091 [PubMed - as supplied by publisher] | | |
| Tissue-Engineered Tracheal Transplantation.
January 12, 2010 at 9:08 AM
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| | Tissue-Engineered Tracheal Transplantation. Transplantation. 2010 Jan 7; Authors: Baiguera S, Birchall MA, Macchiarini P Regenerative medicine offers new tools with which to tackle disorders for which there is currently no good therapeutic option. The trachea is an ideal organ in which to explore the clinical potential of tissue engineering because severe large airway disease is poorly managed by conventional treatments, and the success of a graft is determined only by its ability to conduct air lifelong: that is, whether it can become a sustainable biological conduit. We define the component parts of tissue engineering and review the experimental methods used to produce airway implants to date, including a recent successful, first-in-man experience. PMID: 20061996 [PubMed - as supplied by publisher] | | |
| Modern Surgical Management of Peripheral Nerve Gap.
January 12, 2010 at 9:08 AM
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| | Modern Surgical Management of Peripheral Nerve Gap. J Plast Reconstr Aesthet Surg. 2010 Jan 8; Authors: Pabari A, Yang SY, Seifalian AM, Mosahebi A The management of peripheral nerve injury requires a thorough understanding of the complex physiology of nerve regeneration. The ability to perform surgery under magnification has improved our understanding of the anatomy of the peripheral nerves. However, the level of functional improvement that can be expected following peripheral nerve injury has plateaued. Advancements in the field of tissue engineering have led to an exciting complement of commercially available products that can be used to bridge peripheral nerve gaps. However, the quest for enhanced options is ongoing. This article provides a review of the current treatment options available following peripheral nerve injury, a summary of the published studies using commercially available nerve conduits and nerve allografts in humans and the emerging hopes for the next generation of nerve conduits with the advancement of nanotechnology. PMID: 20061198 [PubMed - as supplied by publisher] | | |
| Impact of heart valve decellularization on 3-D ultrastructure, immunogenicity and thrombogenicity.
January 12, 2010 at 9:08 AM
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| | Impact of heart valve decellularization on 3-D ultrastructure, immunogenicity and thrombogenicity. Biomaterials. 2010 Jan 8; Authors: Zhou J, Fritze O, Schleicher M, Wendel HP, Schenke-Layland K, Harasztosi C, Hu S, Stock UA Decellularized xenogeneic tissue represents an interesting material for heart valve tissue engineering. The prospect objective is removal of all viable cells while preserving extracellular matrix (ECM) integrity. The major concerns of all decellularization protocols remain ECM disruption, immunogenicity and thrombogenicity. Accordingly the aim of this study was visualization of ultrastructural ECM disruption and human immune response and thrombogenicity using different decellularization protocols of porcine heart valves. Porcine pulmonary leaflets were decellularized with four different protocols: sodium deoxycholate, sodium dedecylsulfate, trypsin/EDTA, and trypsin-detergent-nuclease. Then the tissues were processed for histology and two-photon laser scanning microscopy (LSM). For thrombogenicity and immunogenicity testing tissues were incubated with human blood. The histological examination revealed no remaining cells and no significant differences in the ECM hi! stoarchitecture in any group. LSM detected significant ECM alterations in all groups except sodium deoxycholate group with an almost completely preserved ECM. There was no increased immunogenicity between fresh and decellularized tissue. Compared to GA-fixed tissue however significantly increased immune responses and thrombogenicity was observed in all protocols. From our experiment, sodium deoxycholate enables cell removal with almost complete preservation of ECM structures. And all of these four decellularization protocols affected human immunological response and increased thrombogenicity. PMID: 20061016 [PubMed - as supplied by publisher] | | |
| 30. Embryonic and adult stem cell therapy.
January 12, 2010 at 9:08 AM
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| | 30. Embryonic and adult stem cell therapy. J Allergy Clin Immunol. 2010 Jan 8; Authors: Brignier AC, Gewirtz AM There are many types of stem cells. All share the characteristics of being able to self-renew and to give rise to differentiated progeny. Over the last decades, great excitement has been generated by the prospect of being able to exploit these properties for the repair, improvement, and/or replacement of damaged organs. However, many hurdles, both scientific and ethical, remain in the path of using human embryonic stem cells for tissue-engineering purposes. In this report we review current strategies for isolating, enriching, and, most recently, inducing the development of human pluripotent stem cells. In so doing, we discuss the scientific and ethical issues associated with this endeavor. Finally, progress in the use of stem cells as therapies for type 1 diabetes mellitus, congestive heart failure, and various neurologic and immunohematologic disorders, and as vehicles for the delivery of gene therapy, is briefly discussed. PMID: 20061008 [PubMed - as supplied by publisher] | | |
| Microporous bacterial cellulose as a potential scaffold for bone regeneration.
January 12, 2010 at 9:08 AM
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| | Microporous bacterial cellulose as a potential scaffold for bone regeneration. Acta Biomater. 2010 Jan 7; Authors: Zaborowska M, Bodin A, Bäckdahl H, Popp J, Goldstein A, Gatenholm P Nanoporous cellulose biosynthesized by bacteria is an attractive biomaterial scaffold for tissue engineering due to its biocompatibility and good mechanical properties. However, for bone applications a microscopic pore structure is needed to facilitate osteoblast ingrowth and formation of a mineralized tissue. Therefore, in this study microporous bacterial cellulose (BC) scaffolds were prepared by incorporating 300-500 micron paraffin wax microspheres into the fermentation process. The paraffin wax microspheres were subsequently removed, and scanning electron microscopy confirmed a microporous surface of the scaffolds while Fourier transform infrared spectroscopy verified the elimination of paraffin and tensile measurements indicated a Young's modulus of 1.6 MPa. Microporous BC and nanoporous (control) BC scaffolds were seeded with MC3T3-E1 osteoprogenitor cells, and examined by confocal microscopy and histology for cell distribution and mineral deposition. Cells ! clustered within the pores of microporous BC, and formed denser mineral deposits than cells grown on control BC surfaces. This work shows that microporous BC is promising biomaterial for bone tissue engineering applications. PMID: 20060935 [PubMed - as supplied by publisher] | | |
| Therapeutic angiogenesis by autologous bone marrow cell implantation together with allogeneic cultured dermal substitute for intractable ulcers in critical limb ischaemia.
January 12, 2010 at 9:08 AM
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| | Therapeutic angiogenesis by autologous bone marrow cell implantation together with allogeneic cultured dermal substitute for intractable ulcers in critical limb ischaemia. J Plast Reconstr Aesthet Surg. 2010 Jan 7; Authors: Mizuno H, Miyamoto M, Shimamoto M, Koike S, Hyakusoku H, Kuroyanagi Y Therapeutic angiogenesis by autologous bone marrow cell implantation improves blood supply in patients with critical limb ischaemia. In addition, allogeneic cultured dermal substitute is effective for intractable ulcers. The present study determined the effectiveness of bone marrow cell implantation combined with allogeneic cultured dermal substitute in treating severely ischaemic ulcers. We treated eight consecutive patients with severely ischaemic ulcers using this procedure. Stromal cells aspirated from bone marrow were processed to obtain suspensions of mononuclear cells, platelets and endothelial progenitor cells and immediately injected intramuscularly into the lower leg and around the wound, on which allogeneic cultured dermal substitute was applied and changed weekly. Skin ulcers were subsequently closed by skin grafting, if necessary. Angiogenesis was confirmed by postoperative analyses such as ankle-brachial pressure index, angiography, thermography and ! (99m)Technetium-Tetrofosmin perfusion scintigraphy. Above- or below-knee amputation was avoided in all patients and wounds were completely closed in six of them. These results indicate that this combined therapy effectively treated ischaemic ulcers. Since the incidence of this condition might increase in the future, this therapeutic approach should play an important role in the preservation of ischaemic limbs. PMID: 20060793 [PubMed - as supplied by publisher] | | |
| On the biomechanical function of scaffolds for engineering load bearing soft tissues.
January 12, 2010 at 9:08 AM
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| | On the biomechanical function of scaffolds for engineering load bearing soft tissues. Acta Biomater. 2010 Jan 6; Authors: Stella JA, D'Amore A, Wagner WR, Sacks MS Replacement or regeneration of load bearing soft tissues has long been the impetus for the development bioactive materials. While maturing, current efforts continue to be confounded by our lack of understanding of the intricate multi-scale hierarchical arrangements and interactions typically found in native tissues. The current state of the art in biomaterial processing enables a degree of controllable microstructure that can be used for the development of model systems to deduce fundamental biological implications of matrix morphologies on cell function. Furthermore, the development of computational frameworks which allow for the simulation of experimentally derived observations represents a positive departure from what has mostly been an empirically driven field, enabling a deeper understanding of the highly complex biological mechanisms we wish to ultimately emulate. Ongoing research is actively pursuing new materials and processing methods to control material ! structure down to the micro-scale to sustain or improve cell viability, guide tissue growth, and provide mechanical integrity all while exhibiting the capacity to degrade in a controlled manner. The purpose of this review is not to focus solely on material processing but to assess the ability of these techniques to produce mechanically sound tissue surrogates, highlight the unique structural characteristics produced in these materials, and discuss how this translates to distinct macroscopic biomechanical behaviors. PMID: 20060509 [PubMed - as supplied by publisher] | | |
| Fourier transform infrared microspectroscopy identifies early lineage commitment in differentiating human embryonic stem cells.
January 12, 2010 at 9:08 AM
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| | Fourier transform infrared microspectroscopy identifies early lineage commitment in differentiating human embryonic stem cells. Stem Cell Res. 2009 Dec 2; Authors: Heraud P, Ng ES, Caine S, Yu QC, Hirst C, Mayberry R, Bruce A, Wood BR, McNaughton D, Stanley EG, Elefanty AG Human ESCs (hESCs) are a valuable tool for the study of early human development and represent a source of normal differentiated cells for pharmaceutical and biotechnology applications and ultimately for cell replacement therapies. For all applications, it will be necessary to develop assays to validate the efficacy of hESC differentiation. We explored the capacity for FTIR spectroscopy, a technique that rapidly characterises cellular macromolecular composition, to discriminate mesendoderm or ectoderm committed cells from undifferentiated hESCs. Distinct infrared spectroscopic "signatures" readily distinguished hESCs from these early differentiated progeny, with bioinformatic models able to correctly classify over 97% of spectra. These data identify a role for FTIR spectroscopy as a new modality to complement conventional analyses of hESCs and their derivatives. FTIR spectroscopy has the potential to provide low-cost, automatable measurements for the quality contro! l of stem and differentiated cells to be used in industry and regenerative medicine. PMID: 20060373 [PubMed - as supplied by publisher] | | |
| Analysis of Wnt pathway genes during ex vivo expansion and neutrophil differentiation of umbilical cord-blood derived CD34 cells.
January 12, 2010 at 9:08 AM
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| | Analysis of Wnt pathway genes during ex vivo expansion and neutrophil differentiation of umbilical cord-blood derived CD34 cells. Vox Sang. 2010 Jan 4; Authors: Gallagher RC, Tura-Ceide O, Turner M, Barclay R Previous work has shown that optimal ex vivo expansion and differentiation of CD34(+) progenitor cells into neutrophils is by addition of Flt3-L, SCF and G-CSF. Here we report that a variety of genes involved in the WNT pathway are transcriptionally active in both undifferentiated and differentiated umbilical cord blood CD34(+) cells, however statistically significant changes in gene expression are not always consistent across UCB samples. PMID: 20059757 [PubMed - as supplied by publisher] | | |
| Emerging peptide nanomedicine to regenerate tissues and organs.
January 12, 2010 at 9:08 AM
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| | Emerging peptide nanomedicine to regenerate tissues and organs. J Intern Med. 2010 Jan;267(1):71-88 Authors: Webber MJ, Kessler JA, Stupp SI Peptide nanostructures containing bioactive signals offer exciting novel therapies of broad potential impact in regenerative medicine. These nanostructures can be designed through self-assembly strategies and supramolecular chemistry, and have the potential to combine bioactivity for multiple targets with biocompatibility. It is also possible to multiplex their functions by using them to deliver proteins, nucleic acids, drugs and cells. In this review, we illustrate progress made in this new field by our group and others using peptide-based nanotechnology. Specifically, we highlight the use of self-assembling peptide amphiphiles towards applications in the regeneration of the central nervous system, vasculature and hard tissue along with the transplant of islets and the controlled release of nitric oxide to prevent neointimal hyperplasia. Also, we discuss other self-assembling oligopeptide technology and the progress made with these materials towards the developme! nt of potential therapies. PMID: 20059645 [PubMed - in process] | | |
| Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine.
January 12, 2010 at 9:08 AM
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| | Cell sheet engineering: a unique nanotechnology for scaffold-free tissue reconstruction with clinical applications in regenerative medicine. J Intern Med. 2010 Jan;267(1):54-70 Authors: Elloumi-Hannachi I, Yamato M, Okano T Cell sheet technology (CST) is based on the use of thermoresponsive polymers, poly(N-isopropylacrylamide) (PIPAAm). The surface of PIPAAms is formulated in such a way as to make its typical thickness <100 nm. In this review, we first focus on how the methods of PIPAAm-grafted surface preparations and functionalization are important to be able to harvest a functional cell sheet, to be further transplanted. Then, we present aspects of tissue mimics and three-dimensional reconstruction of a tissue in vitro. Finally, we give an overview of clinical applications and clinically relevant animal experimentations of the technology, such as cardiomyopathy, visual acuity, periodonty, oesophageal ulcerations and type 1 diabetes. PMID: 20059644 [PubMed - in process] | | |
| Airway regeneration: the role of the Clara cell secretory protein and the cells that express it.
January 12, 2010 at 9:08 AM
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| | Airway regeneration: the role of the Clara cell secretory protein and the cells that express it. Cytotherapy. 2009;11(6):676-87 Authors: Wong AP, Keating A, Waddell TK Clara cell secretory protein (CCSP) is one of the most abundant proteins in the airway surface fluid, and has many putative functions. Recent advances in the field of stem cells and lung regeneration have identified potentially new roles of CCSP and CCSP-expressing cell populations in airway maintenance, repair and regeneration. This review focuses on the airway regenerative potential of CCSP and the cells that express this protein. The use of this protein or CCSP-expressing cells as an indication of biologic processes that contribute to lung injury or repair is highlighted. PMID: 19878054 [PubMed - indexed for MEDLINE] | | |
| Tissue-engineered allograft tracheal cartilage using fibrin/hyaluronan composite gel and its in vivo implantation.
January 12, 2010 at 9:08 AM
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| | Tissue-engineered allograft tracheal cartilage using fibrin/hyaluronan composite gel and its in vivo implantation. Laryngoscope. 2010 Jan;120(1):30-8 Authors: Kim DY, Pyun J, Choi JW, Kim JH, Lee JS, Shin HA, Kim HJ, Lee HN, Min BH, Cha HE, Kim CH OBJECTIVES/HYPOTHESIS: Treatment and management of tracheal defects remain challenging in head and neck surgery. Various reconstruction techniques have been used, with no consensus on the best approach. The purpose of this study was to explore a novel strategy to fabricate tissue-engineered trachea by using fibrin/hyaluronic acid (HA) composite gel and evaluate the feasibility of creating tracheal cartilage. STUDY DESIGN: A preliminary animal experiment. METHODS: Chondrocytes from rabbit cartilage were expanded and seeded into a culture dish at high density to form mechanically stable allograft tracheal cartilage using fibrin/HA composite gel. After a longitudinal cervical skin incision, the trachea was exposed and a rectangular defect (1 x 0.5 cm) was created on the cervical trachea by scalpel on six rabbits. Tissue-engineered cartilage using fibrin/HA composite was trimmed and fixed to defect boundaries with Tissucol (Baxter International, Deerfield, IL). Postop! eratively, the site was evaluated endoscopically, histologically, radiologically, and functionally. RESULTS: Postoperatively, rigid telescopic examination showed that the implanted scaffolds in all cases were completely covered with regenerated mucosa without granulation or stenosis. Histologic data showed ciliated epithelium regenerated at the operated site from 2 months postoperatively. Ciliary beat frequency of ciliated epithelium on implants was very similar to normal respiratory mucosa. Computed tomography images revealed fine luminal contour of the regenerated site. However, allograft cartilage implanted was found to be partially preserved on the postoperative specimen. CONCLUSIONS: The tracheal luminal contour and functional epithelial regeneration without graft rejection and inflammation were observed after repair of a tracheal resection using allogeneic implants with chondrocytes cultured with fibrin/HA. PMID: 19877186 [PubMed - indexed for MEDLINE] | | |
| Development of a new tissue-engineered sheet for reconstruction of the stomach.
January 12, 2010 at 9:08 AM
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| | Development of a new tissue-engineered sheet for reconstruction of the stomach. Artif Organs. 2009 Oct;33(10):818-26 Authors: Araki M, Tao H, Sato T, Nakajima N, Hyon SH, Nagayasu T, Nakamura T We have developed tissue-engineered digestive tracts composed of collagen scaffold and an inner silicon sheet and successfully used it to repair defects in parts of the esophagus, stomach, and small intestine. However, some improvements were demanded for clinical usage because the silicon sheet presented technical difficulties for suturing and endoscopic removal. New tissue-engineered sheet (New-sheet) was composed of a single-piece and reinforced collagen scaffold with biodegradable copolymer. One beagle dog was used to evaluate whether New-sheet could withstand suturing in comparison with native digestive tracts using a tensile tester. Seven beagle dogs had a 5-cm circular defect created in the stomach. New-sheet soaked with autologous peripheral blood or bone marrow aspirate was sutured to the gastric wall. Endoscopic, histological, and immunohistochemical assessment was performed to evaluate regeneration of the stomach up to 16 weeks. Tensile strength testing ! showed that the mucosal side of New-sheet had strength almost equivalent to the mucosa of the esophagus (P = 0.61). Endoscopically, regeneration of the mucosa started from the circumference after 4 weeks, but a small linear ulcer was still evident at 16 weeks. The regenerated stomach shrank by 60-80% of its original size and histologically showed villous mucosa and underlying dense connective tissue. Immunohistochemically, the regenerated area expressed alpha-smooth-muscle actin but was negative for basic calponin, irrespective of the source of soaked blood. New-sheet shows sufficient strength for suturing, no dehiscence, and better biocompatibility for clinical use, although further examination will be necessary to create a functional digestive tract. PMID: 19839991 [PubMed - indexed for MEDLINE] | | |
| Age-related changes in pericellular hyaluronan organization leads to impaired dermal fibroblast to myofibroblast differentiation.
January 12, 2010 at 9:08 AM
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| | Age-related changes in pericellular hyaluronan organization leads to impaired dermal fibroblast to myofibroblast differentiation. Am J Pathol. 2009 Nov;175(5):1915-28 Authors: Simpson RM, Meran S, Thomas D, Stephens P, Bowen T, Steadman R, Phillips A We have previously demonstrated that transforming growth factor-beta1 (TGF-beta1)-mediated fibroblast-myofibroblast differentiation is associated with accumulation of a hyaluronan (HA) pericellular coat. The current study demonstrates failure of fibroblast-myofibroblast differentiation associated with in vitro aging. This is associated with attenuation of numerous TGF-beta1-dependent responses, including HA synthesis and induction of the HA synthase enzyme HAS2 and the hyaladherin tumor necrosis factor-alpha-stimulated gene 6 (TSG-6), which led to an age-related defect in pericellular HA coat assembly. Inhibition of HAS2-dependent HA synthesis by gene silencing, removal of the HA coat by hyaluronidase digestion, or gene silencing of TSG-6 or cell surface receptor CD44 led to abrogation of TGF-beta1-dependent induction of alpha-smooth muscle actin in "young" cells. This result supports the importance of HAS2-dependent HA synthesis and the HA coat during phenotypic ! activation. Interleukin-1beta stimulation, however, failed to promote phenotypic conversion despite coat formation. A return to basal levels of HA synthesis in aged cells by HAS2 overexpression restored TGF-beta1-dependent induction of TSG-6 and pericellular HA coat assembly. However, this did not lead to the acquisition of a myofibroblast phenotype. Coordinated induction of HAS2 and TSG-6 facilitation of pericellular HA coat assembly is necessary for TGF-beta1-dependent activation of fibroblasts, and both components of this response are impaired with in vitro aging. In conclusion, the HA pericellular coat is integral but not sufficient to correct for the age-dependent defect in phenotypic conversion. PMID: 19808648 [PubMed - indexed for MEDLINE] | | |
| Genome integrity: linking pluripotency and tumorgenicity.
January 12, 2010 at 9:08 AM
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| | Genome integrity: linking pluripotency and tumorgenicity. Trends Genet. 2009 Oct;25(10):425-7 Authors: Deng W, Xu Y Genome integrity is a fundamental issue in both cancer and stem cell biology. A series of recent studies revealed that a tumor suppressor p53, which is required for genome integrity, is critical also for stem cell pluripotency and reprogramming, further strengthening the fundamental link between cancer and pluripotency. p53 and other tumor suppressors might be barriers to reprogramming somatic cells for the generation of induced pluripotent stem cells (iPSCs), and simultaneously and systematically destroying these barriers would improve reprogramming efficiency. Therefore, it is also crucial to determine the tumorgenicity of the cells derived from iPSCs for any future therapeutic use. PMID: 19801173 [PubMed - indexed for MEDLINE] | | |
| Mathematical modelling of tissue-engineered angiogenesis.
January 12, 2010 at 9:08 AM
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| | Mathematical modelling of tissue-engineered angiogenesis. Math Biosci. 2009 Oct;221(2):101-20 Authors: Lemon G, Howard D, Tomlinson MJ, Buttery LD, Rose FR, Waters SL, King JR We present a mathematical model for the vascularisation of a porous scaffold following implantation in vivo. The model is given as a set of coupled non-linear ordinary differential equations (ODEs) which describe the evolution in time of the amounts of the different tissue constituents inside the scaffold. Bifurcation analyses reveal how the extent of scaffold vascularisation changes as a function of the parameter values. For example, it is shown how the loss of seeded cells arising from slow infiltration of vascular tissue can be overcome using a prevascularisation strategy consisting of seeding the scaffold with vascular cells. Using certain assumptions it is shown how the system can be simplified to one which is partially tractable and for which some analysis is given. Limited comparison is also given of the model solutions with experimental data from the chick chorioallantoic membrane (CAM) assay. PMID: 19619562 [PubMed - indexed for MEDLINE] | | |
| Non-hypoxic stabilization of hypoxia-inducible factor alpha (HIF-alpha): relevance in neural progenitor/stem cells.
January 12, 2010 at 9:08 AM
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| | Non-hypoxic stabilization of hypoxia-inducible factor alpha (HIF-alpha): relevance in neural progenitor/stem cells. Neurotox Res. 2009 May;15(4):367-80 Authors: Milosevic J, Adler I, Manaenko A, Schwarz SC, Walkinshaw G, Arend M, Flippin LA, Storch A, Schwarz J Hypoxia-inducible factor-1 (HIF-1) plays an important role in neural progenitor cell (NPC) propagation and dopaminergic differentiation. In the presence of oxygen and iron, hypoxia-inducible factor 1 alpha (HIF-1alpha) is rapidly degraded via the prolyl hydroxylase (PHD)/VHL pathway. In addition to hypoxia, various non-hypoxic stimuli can stabilize HIF-1alpha in NPCs and influence the transcription of HIF-regulated genes. Here, we investigate various hypoxia mimetics: deferoxamine (DFO), ciclopirox olamine (CPX), dimethyloxallyl glycine (DMOG), a novel HIF-PHD inhibitor (FG-4497) and cobalt chloride (CoCl(2)) with respect to their ability to enhance in vitro proliferation, neurogenesis and dopaminergic differentiation of human fetal mesencephalic NPCs (hmNPCs) in ambient oxygen (21%). Although able to stabilize HIF-1alpha, iron chelators (DFO and CPX) and DMOG were toxic to hmNPCs. CoCl(2) was beneficial only towards neuronal and dopaminergic differentiation, whil! e FG-4497 enhanced proliferation, neurogenesis and dopaminergic differentiation of hmNPCs. Both CoCl(2) and FG-4497 were protective to human dopaminergic neurons. Finally, exposure to hyperbaric oxygen (HBO) also stabilized HIF-1alpha in hmNPCs and induced neurogenesis in vitro. These findings suggest that several HIF stabilizing agents or conditions can rescue impaired neurons and promote neurogenesis in vitro. PMID: 19384570 [PubMed - indexed for MEDLINE] | | | |
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