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| BMP-7-loaded PGLA microspheres as a new delivery system for the cultivation of human chondrocytes in a collagen type I gel: the common nude mouse model.
May 18, 2010 at 8:12 AM
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| | BMP-7-loaded PGLA microspheres as a new delivery system for the cultivation of human chondrocytes in a collagen type I gel: the common nude mouse model. Int J Artif Organs. 2010 Jan;33(1):45-53 Authors: Gavenis K, Schneider U, Groll J, Schmidt-Rohlfing B PURPOSE: Bone morphogenic protein 7 (BMP-7) released from polylactide (PLGA) microspheres has proven to be a potent system in cartilage tissue engineering in vitro. However, in vivo data are still lacking. The aim of this study was to investigate this BMP-7 release system utilizing the nude mouse as a small animal model. METHODS: Human osteoarthritic chondrocytes of 10 patients were enzymatically released and transferred into a collagen type-I gel. A concentration of 2x10(5) cells/mL was used. BMP-7 encapsulated in PGLA microspheres was added at an initial concentration of 500 ng BMP-7/mL gel. Untreated specimens and specimens with empty microspheres served as control. Samples were cultivated subcutaneously in nude mice for 6 weeks. RESULTS: After recovery, chondrocytes of all groups displayed a spheroid morphology without signs of dedifferentiation. The proteoglycan and collagen type II content of the control groups was restricted to the immediate pericellular re! gion, whereas treatment group samples showed enhanced collagen type II production. Collagen type II and aggrecan gene expression was enhanced in treatment group samples with respect to the two control groups (mean +/- SD: 0.268 +/- 0.450 to 0.152 +/- 0.129 and 0.155 +/- 0.216 ng/ng beta-actin for collagen type II; 0.535 +/- 0.731 to 0.367 +/- 0.651 and 0.405 +/- 0.326 ng/ng beta-actin for aggrecan), whereas collagen type I gene expression decreased by a factor of 10. Relative protein quantification of collagen type II, collagen type I and proteoglycan was in accordance. CONCLUSIONS: Our data suggest that BMP-7 release from PGLA microspheres led to an improved tissue-engineered cartilage analogue in vivo with an increase in hyaline-cartilage-specific components. PMID: 20474087 [PubMed - in process] | | |
| Establishment of immortalized periodontal ligament progenitor cell line and its behavioural analysis on smooth and rough titanium surface.
May 18, 2010 at 8:12 AM
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| | Establishment of immortalized periodontal ligament progenitor cell line and its behavioural analysis on smooth and rough titanium surface. Eur Cell Mater. 2010;19:228-41 Authors: Docheva D, Padula D, Popov C, Weishaupt P, Prägert M, Miosge N, Hickel R, Böcker W, Clausen-Schaumann H, Schieker M Periodontal ligament (PDL) can be obtained from patients undergoing orthodontic treatment. PDL contains progenitor cells that can be expanded and differentiated towards several mesenchymal lineages in vitro. Furthermore, PDL-derived cells have been shown to generate bone- and PDL-like structures in vivo. Thus, PDL cells, combined with suitable biomaterials, represent a promising tool for periodontitis-related research and PDL engineering. Here, a new PDL cell line using lentiviral gene transfer of human telomerase reverse transcriptase (hTERT) was created. HTERT-expressing PDL cells showed similar morphology and population doubling time but an extended lifespan compared to the primary cells. In addition, PDL-hTERT cells expressed several characteristic genes and upon osteogenic stimulation produced a calcified matrix in vitro. When cultivated on two topographically different titanium scaffolds (MA and SLA), PDL-hTERT cells exhibited augmented spreading, survival a! nd differentiation on smooth (MA) compared to rough (SLA) surfaces. These findings differ from previously reported osteoblast behaviour, but they are in agreement with the behaviour of chondrocytes and gingival fibroblasts, suggesting a very cell type-specific response to different surface textures. In summary, we report the testing of titanium biomaterials using a new PDL-hTERT cell line and propose this cell line as a useful model system for periodontitis research and development of novel strategies for PDL engineering. PMID: 20473831 [PubMed - in process] | | |
| Modified polyelectrolyte complex fibrous scaffold as a matrix for 3D cell culture.
May 18, 2010 at 8:12 AM
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| | Modified polyelectrolyte complex fibrous scaffold as a matrix for 3D cell culture. Biomaterials. 2010 May 14; Authors: Tai BC, Wan AC, Ying JY The paradigm of scaffold tissue engineering relies on the provision of an appropriate environment for cell growth, which includes both structural support and the presentation of cellular signals. In terms of biosignal presentation, fibrous scaffolds by interfacial polyelectrolyte complexation (IPC) offer a clear advantage over other scaffold types as IPC scaffolds are formed using an aqueous-based, room-temperature process compatible with the incorporation of biological molecules. This paper establishes two primary methods for the chemical and biochemical modification of these scaffolds: (i) physical entrapment of the bioactive component, and (ii) covalent binding of the bioactive component. For the first method, extracellular matrix (ECM) proteins, collagen, fibronectin and laminin were drawn into the IPC fiber. For the second method, the cell adhesion peptide, RGD, was chemically conjugated to a thiol-active maleimidylated form of the scaffold. Immobilization of! the bioactive components was characterized by confocal fluorescence microscopy, scanning electron microscopy (SEM) and BCA protein assay. The ECM proteins were distributed throughout the bulk and surface of the fiber. The ratio of covalently bound to physisorbed RGD was approximately 2:3. The performance of the various scaffolds as a matrix to maintain the differentiated function of primary hepatocytes showed that albumin levels in the supernatant were in the order of RGD-modified scaffold>collagen Type I-modified scaffold>fibronectin- or laminin-modified scaffold>unmodified scaffold>plate, while no clear trend in urea production could be discerned. Thus, IPC scaffolds offered a promising platform for the presentation of signals to cells, in this case, to influence their differentiated function. PMID: 20472284 [PubMed - as supplied by publisher] | | |
| Preparation and characterization of coaxial electrospun thermoplastic polyurethane/collagen compound nanofibers for tissue engineering applications.
May 18, 2010 at 8:12 AM
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| | Preparation and characterization of coaxial electrospun thermoplastic polyurethane/collagen compound nanofibers for tissue engineering applications. Colloids Surf B Biointerfaces. 2010 Apr 3; Authors: Chen R, Huang C, Ke Q, He C, Wang H, Mo X Collagen functionalized thermoplastic polyurethane nanofibers (TPU/collagen) were successfully produced by coaxial electrospinning technique with a goal to develop biomedical scaffold. A series of tests were conducted to characterize the compound nanofiber and its membrane in this study. Surface morphology and interior structure of the ultrafine fibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and atomic force microscopy (AFM), whereas the fiber diameter distribution was also measured. The crosslinked membranes were also characterized by SEM. Porosities of different kinds of electrospun mats were determined. The surface chemistry and chemical composition of collagen/TPU coaxial nanofibrous membranes were verified by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectrometry (FTIR). Mechanical measurements were carried out by applying tensile test loads to samples which were prepared fro! m electrospun ultra fine non-woven fiber mats. The coaxial electrospun nanofibers were further investigated as a promising scaffold for PIECs culture. The results demonstrated that coaxial electrospun composite nanofibers had the characters of native extracellular matrix and may be used effectively as an alternative material for tissue engineering and functional biomaterials. PMID: 20471809 [PubMed - as supplied by publisher] | | |
| Comparison of efficiency of terminal differentiation of oligodendrocytes from induced pluripotent stem cells versus embryonic stem cells in vitro.
May 18, 2010 at 8:12 AM
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| | Comparison of efficiency of terminal differentiation of oligodendrocytes from induced pluripotent stem cells versus embryonic stem cells in vitro. J Biosci Bioeng. 2010 Jun;109(6):622-8 Authors: Tokumoto Y, Ogawa S, Nagamune T, Miyake J Oligodendrocytes are the myelinating cells of the central nervous system (CNS), and defects in these cells can result in the loss of CNS functions. Although oligodendrocyte progenitor cells transplantation therapy is an effective cure for such symptoms, there is no readily available source of these cells. Recent studies have described the generation of induced pluripotent stem cells (iPS cells) from somatic cells, leading to anticipation of this technique as a novel therapeutic tool in regenerative medicine. In this study, we evaluated the ability of iPS cells derived from mouse embryonic fibroblasts to differentiate into oligodendrocytes and compared this with the differential ability of mouse embryonic stem cells (ES cells). Experiments using an in vitro oligodendrocyte differentiation protocol that was optimized to ES cells demonstrated that 2.3% of iPS cells differentiated into O4(+) oligodendrocytes compared with 24.0% of ES cells. However, the rate of induct! ion of A2B5(+) oligodendrocyte precursor cell (OPC) was similar for both iPS-derived cells and ES-derived cells (14.1% and 12.6%, respectively). These findings suggest that some intracellular factors in iPS cells inhibit the terminal differentiation of oligodendrocytes from the OPC stage. PMID: 20471604 [PubMed - in process] | | |
| Three dimensional chitin-based scaffolds from Verongida sponges (Demospongiae: Porifera). Part. Isolation and Identification of Chitin.
May 18, 2010 at 8:12 AM
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| | Three dimensional chitin-based scaffolds from Verongida sponges (Demospongiae: Porifera). Part. Isolation and Identification of Chitin. Int J Biol Macromol. 2010 May 12; Authors: Ehrlich H, Ilan M, Maldonado M, Muricy G, Bavestrello G, Kljajic Z, Carballo JL, Shiaparelli S, Ereskovsky A, Schupp P, Born R, Worch H, Bazhenov VV, Kurek D, Varlamow V, Vyalikh D, Kummer K, Sivkov VV, Molodtsov SL, Meissner H, Richter G, Steck E, Richter W, Hunoldt S, Kammer M, Paasch S, Krasokhin V, Patzke G, Brunner E Marine invertebrate organisms including sponges (Porifera) not only provide an abundant source of biologically active secondary metabolites but also inspire investigations to develop biomimetic composites, scaffolds and templates for practical use in materials science, biomedicine and tissue engineering. Here, we presented a detailed study of the structural and physico-chemical properties of three dimensional skeletal scaffolds of the marine sponges Aiolochroia crassa, Aplysina aerophoba, A. cauliformis, A. cavernicola, and A. fulva (Verongida: Demospongiae). We show that these fibrous scaffolds have a multilayered design and are made of chitin. (13)C solid-state NMR spectroscopy, NEXAFS, and IR spectroscopy as well as chitinase digestion and test were applied in order to unequivocally prove the existence of alpha-chitin in all investigated species. PMID: 20471418 [PubMed - as supplied by publisher] | | |
| Resorption rate assessment of adipose tissue-engineered constructs by intravital magnetic resonance imaging.
May 18, 2010 at 8:12 AM
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| | Resorption rate assessment of adipose tissue-engineered constructs by intravital magnetic resonance imaging. J Plast Reconstr Aesthet Surg. 2010 May 12; Authors: Torio-Padron N, Paul D, von Elverfeldt D, Stark GB, Huotari AM Engineering of adipose tissue by implantation of preadipocytes within biodegradable materials has already been extensively reported. However, a method that allows to accurately determine the resorption rate of adipose tissue constructs has not been described to date. The purpose of this study was to determine whether the non-invasive and non-destructive technique of magnetic resonance imaging (MRI) could be used to assess the resorption rate of adipose tissue substitutes after injection of human preadipocytes within fibrin into athymic nude mice. Different concentrations of undifferentiated preadipocytes were injected within fibrin into athymic nude mice. Two days, 3 months and 6 months post-implantation, the mice were anaesthetised and an MRI was performed using a 9.4 Tesla device in order to determine both volume and resorption rate of the implants. Subsequently, the specimens were explanted and qualitative analysis of adipose tissue formation was performed by h! istological examination. After implantation, a progressive resorption of all constructs was macroscopically observed. Implants could be easily visualised and delimited from the surrounding tissues by MRI. Magnetic resonance analysis demonstrated a resorption rate of the implants of 99-100% at 6 months, which was also confirmed by histological analysis. In the remaining implants, formation of human adipose tissue could be immunohistologically confirmed. Here, we show that MRI provides an efficient and non-invasive method for the assessment of implant resorption in adipose tissue engineering. PMID: 20471340 [PubMed - as supplied by publisher] | | |
| Biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces.
May 18, 2010 at 8:12 AM
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| | Biomimetic hybrid scaffolds for engineering human tooth-ligament interfaces. Biomaterials. 2010 May 12; Authors: Park CH, Rios HF, Jin Q, Bland ME, Flanagan CL, Hollister SJ, Giannobile WV A major clinical challenge in the reconstruction of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth-supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. Here, we demonstrate multi-scale computational design and fabrication of composite hybrid polymeric scaffolds for targeted cell transplantation of genetically modified human cells for the formation of human tooth dentin-ligament-bone complexes in vivo. The newly-formed tissues demonstrate the interfacial generation of parallel- and obliquely-oriented fibers that grow and traverse within the polycaprolactone (PCL)-poly(glycolic acid) (PGA) designed constructs forming tooth cementum-like tissue, ligament, and bone structures. This approach offers potential for the clinical implementation of customized periodontal scaffolds that ma! y enable regeneration of multi-tissue interfaces required for oral, dental and craniofacial engineering applications. PMID: 20471083 [PubMed - as supplied by publisher] | | |
| Interactions between meniscal cells and a self assembled biomimetic surface composed of hyaluronic acid, chitosan and meniscal extracellular matrix molecules.
May 18, 2010 at 8:12 AM
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| | Interactions between meniscal cells and a self assembled biomimetic surface composed of hyaluronic acid, chitosan and meniscal extracellular matrix molecules. Biomaterials. 2010 May 12; Authors: Tan GK, Dinnes DL, Butler LN, Cooper-White JJ Menisci are one of the most commonly injured parts of the knee with a limited healing potential. This study focuses on fabrication and characterization of biomimetic surfaces for meniscal tissue engineering. To achieve this, a combination of hyaluronic acid/chitosan (HA/CH) mutilayers with covalently immobilized major extracellular matrix (ECM) components of native meniscus, namely collagen I/II (COL.I/II) and chondroitin-6-sulfate (C6S) was employed. Adsorption of the biomolecules was monitored using a quartz crystal microbalance with dissipation (QCM-D) and fourier transform-surface plasmon resonance (FT-SPR). Immobilization of the biomolecules onto HA/CH mutilayers was achieved by sequential adsorption, with optimum binding at a molar ratio of 1.4:1 (COL.I/II: C6S). After adding COL.I/II, the layers became relatively more rigid and large aggregates were evident. The effects of the modified surfaces on cell proliferation, gene expression and proteoglycan product! ion of rat meniscal cells were examined. Quantitative real-time reverse transcriptase polymerase chain reaction (RT-qPCR) analysis showed that primary meniscal cells dedifferentiated rapidly after one passage in monolayer culture. This process could be reversed by culturing the cells on C6S surfaces, as indicated by increases in both collagen II and aggrecan gene expression, as well as proteoglycan production. Cells with abundant lipid vacuoles were evident on all the surfaces over an extended culture period. The results demonstrate the feasibility of C6S surfaces to avoid the dedifferentiation that normally occurs during monolayer expansion of meniscal cells. PMID: 20471080 [PubMed - as supplied by publisher] | | |
| Amyloid hydrogel derived from curly protein fibrils of alpha-synuclein.
May 18, 2010 at 8:12 AM
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| | Amyloid hydrogel derived from curly protein fibrils of alpha-synuclein. Biomaterials. 2010 May 12; Authors: Bhak G, Lee S, Park JW, Cho S, Paik SR Elucidation of molecular assembly mechanism of protein-based suprastructure formation is pivotal to develop biomaterials. A single amyloidogenic protein of alpha-synuclein turned into two morphologically distinctive amyloid fibrils - 'curly' (CAF) vs. 'straight' (SAF) - depending on its fibrillation processes. Mutually exclusive production of CAF and SAF was achieved with either centrifugal membrane filtration of the preformed oligomeric species of alpha-synuclein or agitated incubation of its monomeric form, representing amyloidogeneses via double-concerted and nucleation-dependent fibrillation model, respectively. Differences in secondary structures of CAF and SAF have been suggested to be responsible for their morphological uniqueness with structural flexibility and mechanical strength. Both polymorphs exerted the self-propagation property, demonstrating that their characteristic morphologies were inherited for two consecutive generations to daughter and grandd! aughter fibrils through the seed-dependent fibrillation procedure. Accumulation of CAF produced amyloid hydrogel composed of fine nano-scaled three-dimensional protein fibrillar network. The hydrogel made of daughter CAF was demonstrated to be a suitable nanomatrix for enzyme entrapment, which protected the entrapped enzyme of horseradish peroxidase from loss of activity due to multiple catalyses and heat treatment. The nano-scaled fibrillar network of CAF, therefore, could exhibit a full potential to be further applied in the promising areas of nanobiotechnology including tissue engineering, drug delivery, nanofiltration and biosensor development. PMID: 20471079 [PubMed - as supplied by publisher] | | |
| Trophic and immunoregulatory properties of neural precursor cells: benefit for intracerebral transplantation.
May 18, 2010 at 8:12 AM
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| | Trophic and immunoregulatory properties of neural precursor cells: benefit for intracerebral transplantation. Exp Neurol. 2010 May 11; Authors: Michel-Monigadon D, Bonnamain V, Nerrière-Daguin V, Dugast AS, Lévèque X, Plat M, Venturi E, Brachet P, Anegon I, Vanhove B, Neveu I, Naveilhan P Intracerebral xenotransplantation of porcine fetal neuroblasts (pNB) is considered as an alternative to human neuroblasts for the treatment of neurodegenerative diseases. However, pNB are systematically rejected, even in an immunoprivileged site such as the brain. Within this context, neural stem/precursor cells (NSPC), which were suggested as exhibiting low immunogenicity, appeared as a useful source of xenogeneic cells. To determine the advantage of using porcine NSPC (pNSPC) in xenotransplantation, pNB and pNSPC were grafted into the striatum of rats without immunosuppression. At Day 63, all the pNB were rejected while 40% of the rats transplanted with pNSPC exhibited large and healthy grafts with numerous pNF70-positive cells. The absence of inflammation at Day 63 and the occasional presence of T cells in pNSPC grafts evoked a weak host immune response which might be partly due to the immunosuppressive properties of the transplanted cells. T cell proliferation! assays confirmed such a hypothesis by revealing an inhibitory effect of pNSPC on T cells through a soluble factor. In addition to their immunosuppressive effect, in contrast to pNB, very few pNSPC differentiated into tyrosine hydroxylase-positive neurons but the cells triggered an intense innervation of the striatum by rat dopaminergic fibers coming from the substantia nigra. Further experiments will be required to optimize the use of pNSPC in regenerative medicine but here we show that their immunomodulatory and trophic activities might be of great interest for restorative strategies. PMID: 20470774 [PubMed - as supplied by publisher] | | |
| Robotic-assisted radical prostatectomy in 2010.
May 18, 2010 at 8:12 AM
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| | Robotic-assisted radical prostatectomy in 2010. Expert Rev Anticancer Ther. 2010 May;10(5):671-82 Authors: Singh I, Hemal AK This article reviews the current status of robotic-assisted radical prostatectomy (RARP) with outcome analysis. The published English literature (PubMed) database was searched extensively for major publications and large series on RARP. The search was carried out over the preceding 3-year period. Selected series were then reviewed, summarized and analyzed for their salient features. A literature search yielded 19 major publications on RARP in the preceding 2 years. A review of the current RARP literature (2006-2009) of multi-institutional cases of RARP demonstrated a mean operating room time, blood loss, hospital stay, positive surgical margin rate and perioperative-complication rate of approximately 194 min, 196 ml, 1.43 days, 25.7% and 5.83 %, respectively (based on the analysis of data using central tendency measures [mean]). The overall potency and continence rates were 73.6 and 87.1%, respectively (based on analysis of the published and reported data). All RA! RP cases were performed with the use of da Vinci robotic system((R)) (Intuitive Surgical, CA, USA). It is expected that in 2010 close to 70% of radical prostatectomies in the USA will be performed with robotic assistance. The patient and surgeon appeal for RARP continues to expand exponentially. It seems pertinent to conclude that increasing experience with RARP may reduce the incidence of positive surgical margins and will improve the functional outcome, which is the challenge at this point in time. Although the early cancer control and intermediate follow-up on functional outcome with RARP appears to be convincing and favorable, the long-term ( approximately 10 years) data are still awaited. PMID: 20470000 [PubMed - in process] | | |
| Effect of neural-induced mesenchymal stem cells and platelet-rich plasma on facial nerve regeneration in an acute nerve injury model.
May 18, 2010 at 8:12 AM
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| | Effect of neural-induced mesenchymal stem cells and platelet-rich plasma on facial nerve regeneration in an acute nerve injury model. Laryngoscope. 2010 May;120(5):907-13 Authors: Cho HH, Jang S, Lee SC, Jeong HS, Park JS, Han JY, Lee KH, Cho YB OBJECTIVES/HYPOTHESIS: The purpose of this study was to investigate the effects of platelet-rich plasma (PRP) and neural-induced human mesenchymal stem cells (nMSCs) on axonal regeneration from a facial nerve axotomy injury in a guinea pig model. STUDY DESIGN: Prospective, controlled animal study. METHODS: Experiments involved the transection and repair of the facial nerve in 24 albino guinea pigs. Four groups were created based on the method of repair: suture only (group I, control group); PRP with suture (group II); nMSCs with suture (group III); and PRP and nMSCs with suture (group IV). Each method of repair was applied immediately after nerve transection. The outcomes measured were: 1) functional outcome measurement (vibrissae and eyelid closure movements); 2) electrophysiologic evaluation; 3) neurotrophic factors assay; and 4) histologic evaluation. RESULTS: With respect to the functional outcome measurement, the functional outcomes improved after transection! and reanastomosis in all groups. The control group was the slowest to demonstrate recovery of movement after transection and reanastomosis. The other three groups (groups II, III, and IV) had significant improvement in function compared to the control group 4 weeks after surgery (P < .05). On the electrophysiologic evaluation, there was significantly better performances in groups II, III, and IV when compared to group I with respect to the amplitude and excitation area of the compound motor action potentials (MAPs) 4 and 6 weeks after surgery (P < .05); group IV had the best performance. A Western blot assay showed that group II had marked expression of several neurotrophic factors. Groups II, III, and IV demonstrated better results in axon counts and myelin thickness when compared with group I. Based on quantitative histology analysis, group IV had the greatest myelinated axon fibers compared to the other groups (P < .05). CONCLUSIONS: The use of PRP and/or nMSCs! promotes facial nerve regeneration in an animal model of faci! al nerve axotomy. The use of nMSCs showed no benefit over the use of PRP in facial nerve regeneration, but the combined use of PRP and nMSCs showed a greater beneficial effect than use of either alone. This study provides evidence for the potential clinical application of PRP and nMSCs in peripheral nerve regeneration of an acute nerve injury. Laryngoscope, 2010. PMID: 20422684 [PubMed - indexed for MEDLINE] | | |
| Injectable tissue-engineered bone repair of a rat calvarial defect.
May 18, 2010 at 8:12 AM
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| | Injectable tissue-engineered bone repair of a rat calvarial defect. Laryngoscope. 2010 May;120(5):895-901 Authors: Stephan SJ, Tholpady SS, Gross B, Petrie-Aronin CE, Botchway EA, Nair LS, Ogle RC, Park SS OBJECTIVES/HYPOTHESIS: Advances in bone repair have focused on the minimally-invasive delivery of tissue-engineered bone (TEB). A promising injectable biopolymer of chitosan and inorganic phosphates was seeded with mesenchymal stem cells (MSCs) and a bone growth factor (BMP-2), and evaluated in a rat calvarial critical size defect (CSD). Green fluorescent protein (GFP)-labeled MSCs are used to evaluate patterns of cell viability and proliferation. STUDY DESIGN: Prospective, controlled trial in an animal model. METHODS: In 30 male rats, 8-mm calvarial CSDs were created, and divided into five groups of six animals each. In the experimental groups, the defects were injected with either chitosan gel, gel loaded with MSCs (0.3 x 10(6) cells/defect), gel loaded with BMP-2 (2 microg/defect), or gel loaded with both MSC and BMP-2. In the control group, the defect was left untreated. At 4 weeks, in vivo microcomputed tomography (micro-CT) analysis was performed. At 8 weeks! , calvarial specimens were examined by micro-CT, histology, and immunohistochemistry. RESULTS: New areas of bone growth were seen in the defects of all treated animals. Micro-CT analysis revealed a significant (P < .001) time-dependent increase in the regeneration of bone volume and bone area in defects treated with gel/MSC/BMP-2 as compared to all other groups. Histological analysis confirmed this difference. GFP-labeled TEB was detected within the areas of new bone, indicating cell viability and contribution to new bone growth by the injected MSC. CONCLUSIONS: This study demonstrates that an injectable form of TEB using a chitosan gel, MSC, and BMP-2 can enhance bone formation in a rat calvarial CSD. PMID: 20422682 [PubMed - indexed for MEDLINE] | | |
| Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.
May 18, 2010 at 8:12 AM
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| | Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia. Nature. 2010 Apr 8;464(7290):852-7 Authors: Raaijmakers MH, Mukherjee S, Guo S, Zhang S, Kobayashi T, Schoonmaker JA, Ebert BL, Al-Shahrour F, Hasserjian RP, Scadden EO, Aung Z, Matza M, Merkenschlager M, Lin C, Rommens JM, Scadden DT Mesenchymal cells contribute to the 'stroma' of most normal and malignant tissues, with specific mesenchymal cells participating in the regulatory niches of stem cells. By examining how mesenchymal osteolineage cells modulate haematopoiesis, here we show that deletion of Dicer1 specifically in mouse osteoprogenitors, but not in mature osteoblasts, disrupts the integrity of haematopoiesis. Myelodysplasia resulted and acute myelogenous leukaemia emerged that had acquired several genetic abnormalities while having intact Dicer1. Examining gene expression altered in osteoprogenitors as a result of Dicer1 deletion showed reduced expression of Sbds, the gene mutated in Schwachman-Bodian-Diamond syndrome-a human bone marrow failure and leukaemia pre-disposition condition. Deletion of Sbds in mouse osteoprogenitors induced bone marrow dysfunction with myelodysplasia. Therefore, perturbation of specific mesenchymal subsets of stromal cells can disorder differentiation, pro! liferation and apoptosis of heterologous cells, and disrupt tissue homeostasis. Furthermore, primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced oncogenesis. PMID: 20305640 [PubMed - indexed for MEDLINE] | | |
| Ex vivo bone morphogenetic protein-2 gene delivery using gingival fibroblasts promotes bone regeneration in rats.
May 18, 2010 at 8:12 AM
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| | Ex vivo bone morphogenetic protein-2 gene delivery using gingival fibroblasts promotes bone regeneration in rats. J Clin Periodontol. 2010 Mar;37(3):305-11 Authors: Shin JH, Kim KH, Kim SH, Koo KT, Kim TI, Seol YJ, Ku Y, Rhyu IC, Chung CP, Lee YM AIM: The aim of the present study was to investigate bone regeneration following ex vivo bone morphogenetic protein-2 (BMP-2) gene delivery using human gingival fibroblasts (HGFs) in rat calvarial defects. MATERIALS AND METHODS: An 8 mm craniotomy defect was created in Sprague-Dawley rats. The animals were divided into four groups: (1) non-grafted group, the defect was left empty; (2) collagen matrix group, the defect was filled with collagen matrix only; (3) HGF group, the defect was filled with non-transduced HGFs on collagen matrix; (4) BMP-2/HGF group, the defect was filled with BMP-2 gene-transduced HGFs on collagen matrix. Animals were sacrificed at 2 and 4 weeks after surgery, and micro-computed tomographic and histologic observations were performed. RESULTS: The BMP-2/HGF group showed promoted osseous healing of calvarial defects, as compared with the other groups. At both 2 and 4 weeks, regenerated bone area was significantly greater in the BMP-2/HGF grou! p than the other three groups. Quite a few number of transplanted HGFs were observed within the regenerated bone tissues. CONCLUSIONS: The results of this study suggest that ex vivo BMP-2 gene delivery induces prominent bone regeneration in vivo and HGFs may be useful as target cells for ex vivo gene therapy. PMID: 20041973 [PubMed - indexed for MEDLINE] | | |
| Anatomical changes in the primary visual cortex of the congenitally blind Crx-/- mouse.
May 18, 2010 at 8:12 AM
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| | Anatomical changes in the primary visual cortex of the congenitally blind Crx-/- mouse. Neuroscience. 2010 Mar 31;166(3):886-98 Authors: Goldshmit Y, Galley S, Foo D, Sernagor E, Bourne JA Mutations in the human cone-rod homeobox (Crx) gene are associated with retinal dystrophies such as Leber Congenital Amaurosis (LCA), characterized by complete or near complete absence of vision from birth. The photoreceptors of Crx-/- mice lack outer segments, and therefore cannot capture light signals through rods and cones, thus resulting in a lack of normal retinal ganglion cell activity from birth. Using specific antibodies to subsets of neurons and markers of activity, we examined the impact of this absence of sensory input on the development of the primary visual cortex (V1) in early postnatal Crx-/- mice, before wiring of the visual system is complete, and in adulthood. We revealed that Crx-/- mice did not exhibit gross anatomical differences in V1; however, they exhibited significantly fewer calcium-binding protein (parvalbumin and calbindin-D28k) expressing interneurons, as well as reduced nonphosphorylated neurofilament expression in V1. These results r! eveal that the Crx mutation and lack of light stimulation through the photoreceptor pathway regulate the development and phenotype of different neuronal populations in V1 but not its general morphology. We conclude, therefore, that photoreceptor-mediated visual input during development is crucial for the normal postnatal development and maturation of subsets of cortical neurons. PMID: 20034544 [PubMed - indexed for MEDLINE] | | | | 
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