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| Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury.
February 25, 2010 at 6:34 AM
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| | Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury. J Vet Sci. 2009 Dec;10(4):273-84 Authors: Ryu HH, Lim JH, Byeon YE, Park JR, Seo MS, Lee YW, Kim WH, Kang KS, Kweon OK In this study, we evaluated if the implantation of allogenic adipose-derived stem cells (ASCs) improved neurological function in a canine spinal cord injury model. Eleven adult dogs were assigned to three groups according to treatment after spinal cord injury by epidural balloon compression: C group (no ASCs treatment as control), V group (vehicle treatment with PBS), and ASC group (ASCs treatment). ASCs or vehicle were injected directly into the injured site 1 week after spinal cord injury. Pelvic limb function after transplantation was evaluated by Olby score. Magnetic resonance imaging, somatosensory evoked potential (SEP), histopathologic and immunohistichemical examinations were also performed. Olby scores in the ASC group increased from 2 weeks after transplantation and were significantly higher than C and V groups until 8 weeks (p < 0.05). However, there were no significant differences between the C and V groups. Nerve conduction velocity based on SEP wa! s significantly improved in the ASC group compared to C and V groups (p < 0.05). Positive areas for Luxol fast blue staining were located at the injured site in the ASC group. Also, GFAP, Tuj-1 and NF160 were observed immunohistochemically in cells derived from implanted ASCs. These results suggested that improvement in neurological function by the transplantation of ASCs in dogs with spinal cord injury may be partially due to the neural differentiation of implanted stem cells. PMID: 19934591 [PubMed - indexed for MEDLINE] | | |
| Resident macrophages influence stem cell activity in the mammary gland.
February 25, 2010 at 6:34 AM
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| | Resident macrophages influence stem cell activity in the mammary gland. Breast Cancer Res. 2009;11(4):R62 Authors: Gyorki DE, Asselin-Labat ML, van Rooijen N, Lindeman GJ, Visvader JE INTRODUCTION : Macrophages in the mammary gland are essential for morphogenesis of the ductal epithelial tree and have been implicated in promoting breast tumor metastasis. Although it is well established that macrophages influence normal mammopoiesis, the mammary cell types that these accessory cells influence have not been determined. Here we have explored a role for macrophages in regulating mammary stem cell (MaSC) activity, by assessing the ability of MaSCs to reconstitute a mammary gland in a macrophage-depleted fat pad. METHODS : Two different in vivo models were used to deplete macrophages from the mouse mammary fat pad, allowing us to examine the effect of macrophage deficiency on the mammary repopulating activity of MaSCs. Both the Csf1op/op mice and clodronate liposome-mediated ablation models entailed transplantation studies using the MaSC-enriched population. RESULTS : We show that mammary repopulating ability is severely compromised when the wild-typ! e MaSC-enriched subpopulation is transplanted into Csf1op/op fat pads. In reciprocal experiments, the MaSC-enriched subpopulation from Csf1op/op glands had reduced regenerative capacity in a wild-type environment. Utilizing an alternative strategy for selective depletion of macrophages from the mammary gland, we demonstrate that co-implantation of the MaSC-enriched subpopulation with clodronate-liposomes leads to a marked decrease in repopulating frequency and outgrowth potential. CONCLUSIONS : Our data reveal a key role for mammary gland macrophages in supporting stem/progenitor cell function and suggest that MaSCs require macrophage-derived factors to be fully functional. Macrophages may therefore constitute part of the mammary stem cell niche. PMID: 19706193 [PubMed - indexed for MEDLINE] | | |
| Retinal afferents synapse with relay cells targeting the middle temporal area in the pulvinar and lateral geniculate nuclei.
February 25, 2010 at 6:30 AM
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| | Retinal afferents synapse with relay cells targeting the middle temporal area in the pulvinar and lateral geniculate nuclei. Front Neuroanat. 2010;4:8 Authors: Warner CE, Goldshmit Y, Bourne JA Considerable debate continues regarding thalamic inputs to the middle temporal area (MT) of the visual cortex that bypass the primary visual cortex (V1) and the role they might have in the residual visual capability following a lesion of V1. Two specific retinothalamic projections to area MT have been speculated to relay through the medial portion of the inferior pulvinar nucleus (PIm) and the koniocellular layers of the dorsal lateral geniculate nucleus (LGN). Although a number of studies have demonstrated retinal inputs to regions of the thalamus where relays to area MT have been observed, the relationship between the retinal terminals and area MT relay cells has not been established. Here we examined direct retino-recipient regions of the marmoset monkey (Callithrix jacchus) pulvinar nucleus and the LGN following binocular injections of anterograde tracer, as well as area MT relay cells in these nuclei by injection of retrograde tracer into area MT. Retinal aff! erents were shown to synapse with area MT relay cells as demonstrated by colocalization with the presynaptic vesicle membrane protein synaptophysin. We also established the presence of direct synapes of retinal afferents on area MT relay cells within the PIm, as well as the koniocellular K1 and K3 layers of the LGN, thereby corroborating the existence of two disynaptic pathways from the retina to area MT that bypass V1. PMID: 20179789 [PubMed - in process] | | |
| Low Oxygen Tension and Synthetic Nanogratings Improve the Uniformity and Stemness of Human Mesenchymal Stem Cell Layer.
February 25, 2010 at 6:30 AM
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| | Low Oxygen Tension and Synthetic Nanogratings Improve the Uniformity and Stemness of Human Mesenchymal Stem Cell Layer. Mol Ther. 2010 Feb 23; Authors: Zhao F, Veldhuis JJ, Duan Y, Yang Y, Christoforou N, Ma T, Leong KW A free-standing, robust cell sheet comprising aligned human mesenchymal stem cells (hMSCs) offers many interesting opportunities for tissue reconstruction. As a first step toward this goal, a confluent, uniform hMSC layer with a high degree of alignment and stemness maintenance needs to be created. Hypothesizing that topographical cue and a physiologically relevant low-oxygen condition could promote the formation of such an hMSC layer, we studied the culture of hMSCs on synthetic nanogratings (350 nm width and 700 nm pitch) and either under 2 or 20% O(2). Culturing hMSCs on the nanogratings highly aligned the cells, but it tended to create patchy layers and accentuate the hMSC differentiation. The 2% O(2) improved the alignment and uniformity of hMSCs, and reduced their differentiation. Over a 14-day culture period, hMSCs in 2% O(2) showed uniform connexon distribution, secreted abundant extracellular matrix (ECM) proteins, and displayed a high progenicity. After ! 21-day culture on nanogratings, hMSCs exposed to 2% O(2) maintained a higher viability and differentiation capacity. This study established that a 2% O(2) culture condition could restrict the differentiation of hMSCs cultured on nanopatterns, thereby setting the foundation to fabricate a uniformly aligned hMSC sheet for different regenerative medicine applications. PMID: 20179678 [PubMed - as supplied by publisher] | | |
| Transcriptomics approach to investigate zebrafish heart regeneration.
February 25, 2010 at 6:30 AM
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| | Transcriptomics approach to investigate zebrafish heart regeneration. J Cardiovasc Med (Hagerstown). 2010 Feb 22; Authors: Sleep E, Boué S, Jopling C, Raya M, Raya A, Belmonte JC In mammals, after a myocardial infarction episode, the damaged myocardium is replaced by scar tissue with negligible cardiomyocyte proliferation. Zebrafish, in contrast, display an extensive regenerative capacity, as they are able to restore completely lost cardiac tissue after partial ventricular amputation. Although questions about the early signals that drive the regenerative response and the relative role of each cardiac cell type in this process still need to be answered, the zebrafish is emerging as a very valuable tool to understand heart regeneration and to devise strategies that may be of potential value to treat human cardiac disease. Here, we performed a genome-wide transcriptome profile analysis focusing on the early time points of zebrafish heart regeneration and compared our results with those of previously published data. Our analyses confirmed the differential expression of several transcripts and identified additional genes whose expression is dif! ferentially regulated during zebrafish heart regeneration. We validated the microarray data by conventional and/or quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). For a subset of these genes, their expression pattern was analyzed by in-situ hybridization and shown to be upregulated in the regenerating area of the heart. Our results offer new insights into the biology of heart regeneration in the zebrafish and, together with future experiments in mammals, may be of potential interest for clinical applications. PMID: 20179605 [PubMed - as supplied by publisher] | | |
| Science signaling podcast: 23 february 2010.
February 25, 2010 at 6:30 AM
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| | Science signaling podcast: 23 february 2010. Sci Signal. 2010;3(110):pc5 Authors: Li CY, Vanhook AM This is a conversation with Chuan-Yuan Li about a Research Article published in the 23 February 2010 issue of Science Signaling. PMID: 20179268 [PubMed - in process] | | |
| Nfix Regulates Fetal-Specific Transcription in Developing Skeletal Muscle.
February 25, 2010 at 6:30 AM
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| | Nfix Regulates Fetal-Specific Transcription in Developing Skeletal Muscle. Cell. 2010 Feb 19;140(4):554-566 Authors: Messina G, Biressi S, Monteverde S, Magli A, Cassano M, Perani L, Roncaglia E, Tagliafico E, Starnes L, Campbell CE, Grossi M, Goldhamer DJ, Gronostajski RM, Cossu G Skeletal myogenesis, like hematopoiesis, occurs in successive developmental stages that involve different cell populations and expression of different genes. We show here that the transcription factor nuclear factor one X (Nfix), whose expression is activated by Pax7 in fetal muscle, in turn activates the transcription of fetal specific genes such as MCK and beta-enolase while repressing embryonic genes such as slow myosin. In the case of the MCK promoter, Nfix forms a complex with PKC theta that binds, phosphorylates, and activates MEF2A. Premature expression of Nfix activates fetal and suppresses embryonic genes in embryonic muscle, whereas muscle-specific ablation of Nfix prevents fetal and maintains embryonic gene expression in the fetus. Therefore, Nfix acts as a transcriptional switch from embryonic to fetal myogenesis. PMID: 20178747 [PubMed - as supplied by publisher] | | |
| Highlight: 'regenerative hepatology'.
February 25, 2010 at 6:30 AM
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| | Highlight: 'regenerative hepatology'. Biol Chem. 2009 Oct;390(10):949-50 Authors: Häussinger D, Sies H PMID: 19764897 [PubMed - indexed for MEDLINE] | | |
| Modular Tissue Engineering: Engineering Biological Tissues from the Bottom Up.
February 25, 2010 at 6:11 AM
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| | Modular Tissue Engineering: Engineering Biological Tissues from the Bottom Up. Soft Matter. 2009;5(7):1312-1319 Authors: Nichol JW, Khademhosseini A Tissue engineering creates biological tissues that aim to improve the function of diseased or damaged tissues. To enhance the function of engineered tissues there is a need to generate structures that mimic the intricate architecture and complexity of native organs and tissues. With the desire to create more complex tissues with features such as developed and functional microvasculature, cell binding motifs and tissue specific morphology, tissue engineering techniques are beginning to focus on building modular microtissues with repeated functional units. The emerging field known as modular tissue engineering focuses on fabricating tissue building blocks with specific microarchitectural features and using these modular units to engineer biological tissues from the bottom up. In this review we will examine the promise and shortcomings of "bottom-up" approaches to creating engineered biological tissues. Specifically, we will survey the current techniques for controll! ing cell aggregation, proliferation and extracellular matrix deposition, as well as approaches to generating shape-controlled tissue modules. We will then highlight techniques utilized to create macroscale engineered biological tissues from modular microscale units. PMID: 20179781 [PubMed - as supplied by publisher] | | |
| A novel seamless elastic scaffold for vascular tissue engineering.
February 25, 2010 at 6:11 AM
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| | A novel seamless elastic scaffold for vascular tissue engineering. J Biomater Sci Polym Ed. 2010;21(3):289-302 Authors: Kim SH, Chung E, Kim SH, Jung Y, Kim YH, Kim SH Tissue-engineered vascular grafts have been investigated as a substitute for prosthetic vascular grafts. The current scaffolds have several limitations due to weak mechanical properties in withstanding the pressure of blood vessel. A gel-spinning molding device including three-separate drivers that make a cylindrical shaft turn on its axis, orbit, and concurrently move up and down was developed for preparing seamless fibrous tubular scaffolds for vascular grafts. A seamless double-layered tubular scaffold, which was composed of an outer fibrous network and inner porous layer, was fabricated by using the device for the spinning of poly(L-lactide-co-caprolactone) (PLCL, 50:50) solution as a gel state on a rotating cylindrical shaft that had been dip-coated with the mixture of PLCL solution and NaCl particles. A scaffold that had an inner layer fabricated with 30% salts, below 20 mum in salt size, and more than 100 mum in thickness, was found to be optimal from a blo! od leakage test. The burst pressures of the scaffolds were more than 900 mmHg. The scaffolds exhibited 550-670% elongation-at-break. The measured circumferential and longitudinal tensile strengths of the scaffolds were 3.62 +/- 0.68 and 2.64 +/- 0.41 MPa, respectively. The suture retention strength of the scaffold was measured to be 7.68 +/- 0.75 N. These mechanically strong and elastic properties of the newly developed scaffolds provide an important basis for blood vessel tissue engineering. PMID: 20178686 [PubMed - in process] | | |
| IGF-1 and GDF-5 Promote the Formation of Tissue-engineered Human Nasal Septal Cartilage.
February 25, 2010 at 6:11 AM
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| | IGF-1 and GDF-5 Promote the Formation of Tissue-engineered Human Nasal Septal Cartilage. Tissue Eng Part C Methods. 2010 Feb 23; Authors: Alexander TH, Sage AB, Chen AC, Schumacher BL, Shelton E, Masuda K, Sah RL, Watson D Introduction: Tissue-engineering of human nasal septal chondrocytes offers the potential to create large quantities of autologous material for use in reconstructive surgery of the head and neck. Culture with recombinant human growth factors may improve the biochemical and biomechanical properties of engineered tissue. The objectives of this study were to: (1) perform a high throughput screen to assess multiple combinations of growth factors and (2) perform more detailed testing of candidates identified in part 1. Methods: In part 1, human nasal septal chondrocytes from 3 donors were expanded in monolayer with pooled human serum (HS). Cells were then embedded in alginate beads for 2 weeks of culture in medium supplemented with 2% or 10% HS and one of 90 different growth factor combinations. Combinations of IGF-1, BMP-2, BMP-7, BMP-13, GDF-5, TGFss-2, insulin, and dexamethasone were evaluated. Glycosaminoglycan (GAG) accumulation was measured. A combination of IGF-1! and GDF-5 was selected for further testing based on the results of part 1. Chondrocytes from 4 donors underwent expansion followed by 3D alginate culture for 2 weeks in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5. Chondrocytes and their associated matrix were then recovered and cultured for 4 weeks in 12 mm transwells in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5 (the same medium used for alginate culture). Biochemical and biomechanical properties of the neocartilage were measured. Results: In part 1, GAG accumulation was highest for growth factor combinations including both IGF-1 and GDF-5. In part 2, the addition of IGF-1 and GDF-5 to 2% HS resulted in a 12-fold increase in construct thickness compared to 2% HS alone (p < 0.0001). GAG and type II collagen accumulation were significantly higher with IGF-1 and GDF-5. Confined compression modulus was greatest with 2% HS, IGF-1, and GDF-5. Conclusion: Supplementation of! medium with IGF-1 and GDF-5 during creation of neocartilage c! onstruct s results in increased accumulation of GAG and type II collagen and improved biomechanical properties compared to constructs created without the growth factors. PMID: 20178406 [PubMed - as supplied by publisher] | | |
| Biomedical applications of functionalized fullerene-based nanomaterials.
February 25, 2010 at 6:11 AM
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| | Biomedical applications of functionalized fullerene-based nanomaterials. Int J Nanomedicine. 2009;4:261-75 Authors: Partha R, Conyers JL Since their discovery in 1985, fullerenes have been investigated extensively due to their unique physical and chemical properties. In recent years, studies on functionalized fullerenes for various applications in the field of biomedical sciences have seen a significant increase. The ultimate goal is towards employing these functionalized fullerenes in the diagnosis and therapy of human diseases. Functionalized fullerenes are one of the many different classes of compounds that are currently being investigated in the rapidly emerging field of nanomedicine. In this review, the focus is on the three categories of drug delivery, reactive oxygen species quenching, and targeted imaging for which functionalized fullerenes have been studied in depth. In addition, an exhaustive list of the different classes of functionalized fullerenes along with their applications is provided. We will also discuss and summarize the unique approaches, mechanisms, advantages, and the aspect ! of toxicity behind utilizing functionalized fullerenes for biomedical applications. PMID: 20011243 [PubMed - indexed for MEDLINE] | | |
| Gingival fibroblasts established on microstructured model surfaces: their influence on epithelial morphogenesis and other tissue-specific cell functions in a co-cultured epithelium: an in-vitro model.
February 25, 2010 at 6:11 AM
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| | Gingival fibroblasts established on microstructured model surfaces: their influence on epithelial morphogenesis and other tissue-specific cell functions in a co-cultured epithelium: an in-vitro model. J Orofac Orthop. 2009 Sep;70(5):351-62 Authors: Müssig E, Tomakidi P, Steinberg T OBJECTIVE: The objective of this study was to investigate how gingival fibroblasts cultured on microstructured model surfaces affect epithelial morphogenesis and other cell functions in a cocultured epithelium while conducting a molecular analysis of interactions between biomaterials employing periodontal tissue cells. MATERIALS AND METHODS: We are the first to have successfully co-cultured gingival fibroblasts together with gingival keratinocytes on biofunctionalized, microstructured model surfaces and, in the resulting co-cultured epithelium, examined the molecules of tissue homeostasis, the differentiation marker keratin (K) 1/10, and involucrin after 1- and 2-week periods of cultivation. Desmoplakin was perceived as evidence of cell-to-cell contact and thus as proof of epithelial integrity. We also analyzed the basement membrane component laminin-5. The aforementioned co-culture model without gingival fibroblasts was used as a control set-up. RESULTS: On the p! rotein level, indirect immunofluorescence demonstrated the presence of K1/10, involucrin and the basement membrane component laminin-5 in the co-cultured epithelium in both culture periods. Furthermore, we observed that these epithelial markers had become re-oriented toward the suprabasal cell layers which, in turn, reflects the native in-vivo gingival epithelium. We identified cell-to-cell adhesion as a function of desmoplakin after just 1 week. In the mRNA analysis using quantitative RT-PCR after 2 weeks of cultivation, we noted a considerable rise in relative gene expression that was time-dependent for the early keratinocyte differentiation marker K1 and late marker involucrin. CONCLUSIONS: Our findings demonstrate that gingival fibroblasts on microstructured model surfaces are vitally important for tissue- specific cell functions such as epithelial morphogenesis and other biological cell functions such as differentiation and epithelial integrity. These study findings ca! n thus contribute to the optimization and/or new development o! f biomat erials currently used in dental medicine. PMID: 19997994 [PubMed - indexed for MEDLINE] | | | | 
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