| In situ tissue engineering of canine skull with guided bone regeneration.
September 15, 2009 at 7:17 am
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| | In situ tissue engineering of canine skull with guided bone regeneration. Acta Otolaryngol. 2009 Sep 11;:1-10 Authors: Umeda H, Kanemaru SI, Yamashita M, Ohno T, Suehiro A, Tamura Y, Hirano S, Nakamura T, Omori K, Ito J Conclusion: Calcium alginate (CA) membrane prevents excessive fibrous tissue intrusion and/or dislocation of a bone scaffold. However, CA membrane did not always accelerate cranial bone regeneration. Objective: We previously reported skull regeneration using a bone substitute material (BSM), which consisted of collagen-coated beta-tricalcium phosphate and autologous bone fragments, and bone marrow-derived stromal cells (BSCs). However, excessive fibrous tissue intrusion or dislocation of the BSM occasionally interrupted bone regeneration. To avoid such problems, we examined CA membrane, which is useful for guided bone regeneration (GBR), to investigate whether this material maintains the bone regenerative space. Materials and methods: Bone defects (2x2 cm) were created in the skulls of 12 adult beagle dogs using the same clinical procedure. Four experimental models were tested with or without BSM plus BSCs or CA membrane. In group I, the original free bone flap was replaced at the defect. In group II, after replacing the bone flap, the defect was covered with CA membrane. In group III, BSM plus BSCs were used as a gap filler. In group IV, BSM plus BSCs and CA membrane were applied. Histological examinations were performed 3 and 6 months after the operation. Results: In groups I and II, bone regeneration was not observed but fibrous tissue intrusion was prevented in group II. Bone neogenesis was more observed in group III than in group IV at 3 months (p<0.05). At 6 months, the regenerated areas were larger than those observed at 3 months, but the differences between groups III and IV were not statistically significant. PMID: 19750397 [PubMed - as supplied by publisher] |
| Injectable Biomaterials for Regenerating Complex Craniofacial Tissues.
September 15, 2009 at 7:17 am
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| | Injectable Biomaterials for Regenerating Complex Craniofacial Tissues. Adv Mater Deerfield. 2009 Apr 20;21(32-33):3368-3393 Authors: Kretlow JD, Young S, Klouda L, Wong M, Mikos AG Engineering complex tissues requires a precisely formulated combination of cells, spatiotemporally released bioactive factors, and a specialized scaffold support system. Injectable materials, particularly those delivered in aqueous solution, are considered ideal delivery vehicles for cells and bioactive factors and can also be delivered through minimally invasive methods and fill complex 3D shapes. In this review, we examine injectable materials that form scaffolds or networks capable of both replacing tissue function early after delivery and supporting tissue regeneration over a time period of weeks to months. The use of these materials for tissue engineering within the craniofacial complex is challenging but ideal as many highly specialized and functional tissues reside within a small volume in the craniofacial structures and the need for minimally invasive interventions is desirable due to aesthetic considerations. Current biomaterials and strategies used to treat craniofacial defects are examined, followed by a review of craniofacial tissue engineering, and finally an examination of current technologies used for injectable scaffold development and drug and cell delivery using these materials. PMID: 19750143 [PubMed - as supplied by publisher] |
| Identification of phenotypic discriminating markers for intervertebral disc cells and articular chondrocytes.
September 15, 2009 at 7:17 am
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| | Identification of phenotypic discriminating markers for intervertebral disc cells and articular chondrocytes. Rheumatology (Oxford). 2009 Sep 11; Authors: Clouet J, Grimandi G, Pot-Vaucel M, Masson M, Fellah HB, Guigand L, Cherel Y, Bord E, Rannou F, Weiss P, Guicheux J, Vinatier C Objective. The present study was conducted to improve our knowledge of intervertebral disc (IVD) cell biology by comparing the phenotype of nucleus pulposus (NP) and annulus fibrosus (AF) cells with that of articular chondrocytes (ACs). Methods. Rabbit cells from NP and AF were isolated and their phenotype was compared with that of AC by real-time PCR analysis of type I (COL1A1), II (COL2A1) and V (COL5A1) collagens, aggrecan transcript (AGC1), matrix Gla protein (MGP) and Htra serine peptidase 1 (Htra1). Results. Transcript analysis indicated that despite certain similarities, IVD cells exhibit distinct COL2A1/COL1A1 and COL2A1/AGC1 ratios as compared with AC. The expression pattern of COL5A1, MGP and Htra1 makes it possible to define a phenotypic signature for NP and AF cells. Conclusions. Our study shows that NP and AF cells exhibit a clearly distinguishable phenotype from that of AC. Type V collagen, MGP and HtrA1 could greatly help to discriminate among NP, AF and AC cells. PMID: 19748963 [PubMed - as supplied by publisher] |
| Characterization of valvular interstitial cell function in three dimensional matrix metalloproteinase degradable PEG hydrogels.
September 15, 2009 at 7:17 am
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| | Characterization of valvular interstitial cell function in three dimensional matrix metalloproteinase degradable PEG hydrogels. Biomaterials. 2009 Sep 9; Authors: Benton JA, Fairbanks BD, Anseth KS Valvular interstitial cells (VICs) maintain functional heart valve structure and display transient fibroblast and myofibroblast properties. Most cell characterization studies have been performed on plastic dishes; while insightful, these systems are limited. Thus, a matrix metalloproteinase (MMP) degradable poly(ethylene glycol) (PEG) hydrogel system is proposed in this communication as a useful tool for characterizing VIC function in 3D. When encapsulated, VICs attained spread morphology, and proliferated and migrated as shown through real-time cell microscopy. Additionally, fibronectin derived pendant RGD was incorporated into the system to promote integrin binding. As RGD concentration increased from 0 to 2000mum, VIC process extension and integrin alpha(v)beta(3) binding increased within two days. By day 10, integrin binding was equalized between conditions. VIC morphology and rate of process extension were also increased through decreasing the hydrogel matrix density presented to the cells. VIC differentiation in response to exogenously delivered transforming growth factor-beta1 (TGF-beta1) was also examined within the hydrogel networks. TGF-beta1 increased expression of alpha smooth muscle actin (alphaSMA) and collagen-1 at both the mRNA and protein level by day 2 of culture, indicating myofibroblast differentiation, and was sustained over the course of the study (2 weeks). These studies demonstrate the utility, flexibility, and biological activity of this MMP-degradable system for the characterization of VICs, an important cell population for tissue engineering viable valve replacements and understanding valvular pathobiology. PMID: 19747725 [PubMed - as supplied by publisher] |
| Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage.
September 15, 2009 at 7:17 am
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| | Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage. Osteoarthritis Cartilage. 2009 Sep 1; Authors: Torzilli PA, Bhargava M, Park S, Chen CT OBJECTIVE: Osteoarthritis is a disease process of cellular degradation of articular cartilage caused by mechanical loads and inflammatory cytokines. We studied the cellular response in native cartilage subjected to a mechanical load administered simultaneously with an inflammatory cytokine interleukin-1 (IL-1), hypothesizing that the combination of load and cytokine would result in accelerated extracellular matrix (ECM) degradation. METHODS: Mature bovine articular cartilage was loaded for 3 days (stimulation) with 0.2 and 0.5MPa stresses, with and without IL-1 (IL-1alpha, 10ng/ml), followed by 3 days of no stimulation (recovery). Aggrecan and collagen loss were measured as well as aggrecan cleavage using monoclonal antibodies AF-28 and BC-3 for cleavage by aggrecanases (ADAMTS) and matrix metalloproteinases (MMPs), respectively. RESULTS: Incubation with IL-1 caused aggrecan cleavage by aggrecanases and MMPs during the 3 days of stimulation. A load of 0.5MPa inhibited the IL-1-induced aggrecan loss while no inhibition was found for the 0.2MPa stress. There was no collagen loss during the treatments but upon load and IL-1 removal proteoglycan and collagen loss increased. Load itself under these conditions was found to have no effect when compared to the unloaded controls. CONCLUSIONS: A mechanical load of sufficient magnitude can inhibit ECM degradation by chondrocytes when stimulated by IL-1. The molecular mechanisms involved in this process are not clear but probably involve altered mechanochemical signal transduction between the ECM and chondrocyte. PMID: 19747586 [PubMed - as supplied by publisher] |
| Adult Neurogenesis, Neural Stem cells and Alzheimer's Disease: Developments, Limitations, Problems and Promises.
September 15, 2009 at 7:17 am
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| | Adult Neurogenesis, Neural Stem cells and Alzheimer's Disease: Developments, Limitations, Problems and Promises. Curr Alzheimer Res. 2009 Sep 13; Authors: Taupin P Alzheimer's disease (AD) is an irreversible progressive neurodegenerative disease, leading to severe incapacity and death. It is the most common form of dementia among older people. AD is characterized in the brain by amyloid plaques, neurofibrillary tangles, neuronal degeneration, aneuploidy and enhanced neurogenesis and by cognitive, behavioral and physical impairments. Inherited mutations in several genes and genetic, acquired and environmental risk factors have been reported as causes for developing the disease, for which there is currently no cure. Current treatments for AD involve drugs and occupational therapies, and future developments involve early diagnosis and stem cell therapy. In this manuscript, we will review and discuss the recent developments, limitations, problems and promises on AD, particularly related to aneuploidy, adult neurogenesis, neural stem cells (NSCs) and cellular therapy. Though adult neurogenesis may be beneficial for regeneration of the nervous system, it may underly the pathogenesis of AD. Cellular therapy is a promising strategy for AD. Limitations in protocols to establish homogeneous populations of neural progenitor and stem cells and niches for neurogenesis need to be resolved and unlocked, for the full potential of adult NSCs to be realized for therapy. PMID: 19747153 [PubMed - as supplied by publisher] |
| Plant Polyphenols and Tumors: From Mechanisms to Therapies, Prevention, and Protection Against Toxicity of Anti-Cancer Treatments.
September 15, 2009 at 7:17 am
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| | Plant Polyphenols and Tumors: From Mechanisms to Therapies, Prevention, and Protection Against Toxicity of Anti-Cancer Treatments. Curr Med Chem. 2009 Sep 13; Authors: Korkina LG, De Luca C, Kostyuk VA, Pastore S Polyphenolic molecules produced by higher plants in response to biotic and abiotic stresses exert numerous effects on tumorigenic cell transformation, and on tumor cells in vitro and in vivo, and may interact with conventional anti-tumor therapies. In the present review, we collected and critically discussed data on: (i) redox-dependent and redox-independent mechanisms underlying cytotoxic/cytostatic effects of PPs and their metabolites towards tumor cells and cytoprotection of normal cells; (ii) mechanisms of anti-angiogenic and anti-metastatic action of PPs; (iii) PPs-associated phototoxicity against tumor cells and photoprotection of non-tumor cells; (iv) PPs effects on drug-metabolizing enzymes as a basis for their synergism or antagonism with chemotherapy; (v) molecular pathways leading to tumor chemoprevention by PPs; and (vi) PPs as protectors against toxic effects of chemo-, radio-, and photodynamic therapies. PMID: 19747130 [PubMed - as supplied by publisher] |
| Photo-Cross-Linked Hydrogels from Thermoresponsive PEGMEMA-PPGMA-EGDMA Copolymers Containing Multiple Methacrylate Groups: Mechanical Property, Swelling, Protein Release, and Cytotoxicity.
September 15, 2009 at 7:17 am
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| | Photo-Cross-Linked Hydrogels from Thermoresponsive PEGMEMA-PPGMA-EGDMA Copolymers Containing Multiple Methacrylate Groups: Mechanical Property, Swelling, Protein Release, and Cytotoxicity. Biomacromolecules. 2009 Sep 11; Authors: Tai H, Howard D, Takae S, Wang W, Vermonden T, Hennink WE, Stayton PS, Hoffman AS, Endruweit A, Alexander C, Howdle SM, Shakesheff KM Photo-cross-linked hydrogels from thermoresponsive polymers can be used as advanced injectable biomaterials via a combination of physical interaction (in situ thermal gelation) and covalent cross-links (in situ photopolymerization). This can lead to gels with significantly enhanced mechanical properties compared to non-photo-cross-linked thermoresponsive hydrogels. Moreover, the thermally phase-separated gels have attractive advantages over non-thermoresponsive gels because thermal gelation upon injection allows easy handling and holds the shape of the gels prior to photopolymerization. In this study, water-soluble thermoresponsive copolymers containing multiple methacrylate groups were synthesized via one-step deactivation enhanced atom transfer radical polymerization (ATRP) of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M(n) = 475), poly(propylene glycol) methacrylate (PPGMA, M(n) = 375), and ethylene glycol dimethacrylate (EGDMA) and were used to form covalent cross-linked hydrogels by photopolymerization. The cross-linking density was found to have a significant influence on the mechanical and swelling properties of the photo-cross-linked gels. Release studies using lysozyme as a model protein demonstrated a sustained release profile that varied dependent on the copolymer composition, cross-linking density, and the temperature. Mouse C2C12 myoblast cells were cultured in the presence of the copolymers at concentrations up to 1 mg/mL. It was found that the majority of the cells remained viable, as assessed by Alamar Blue, lactate dehydrogenase (LDH), and Live/Dead cell viability/cytotoxicity assays. These studies demonstrate that thermoresponsive PEGMEMA-PPGMA-EGDMA copolymers offer potential as in situ photopolymerizable materials for tissue engineering and drug delivery applications through a combination of facile synthesis, enhanced mechanical properties, tunable cross-linking density, low cytotoxicity, and accessible functionality for further structure modifications. PMID: 19746967 [PubMed - as supplied by publisher] |
| Biomaterials for promoting brain protection, repair and regeneration.
September 15, 2009 at 7:17 am
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| | Biomaterials for promoting brain protection, repair and regeneration. Nat Rev Neurosci. 2009 Sep;10(9):682-92 Authors: Orive G, Anitua E, Pedraz JL, Emerich DF Biomaterials are likely to have an increasingly important role in the treatment of nervous system disorders. Recently developed biomaterials can enable and augment the targeted delivery of drugs or therapeutic proteins to the brain, allow cell or tissue transplants to be effectively delivered to the brain and help to rebuild damaged circuits. Similarly, biomaterials are being used to promote regeneration and to repair damaged neuronal pathways in combination with stem cell therapies. Many of these approaches are gaining momentum because nanotechnology allows greater control over material-cell interactions that induce specific developmental processes and cellular responses including differentiation, migration and outgrowth. PMID: 19654582 [PubMed - indexed for MEDLINE] |
| Chd1 regulates open chromatin and pluripotency of embryonic stem cells.
September 15, 2009 at 7:17 am
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| | Chd1 regulates open chromatin and pluripotency of embryonic stem cells. Nature. 2009 Aug 13;460(7257):863-8 Authors: Gaspar-Maia A, Alajem A, Polesso F, Sridharan R, Mason MJ, Heidersbach A, Ramalho-Santos J, McManus MT, Plath K, Meshorer E, Ramalho-Santos M An open chromatin largely devoid of heterochromatin is a hallmark of stem cells. It remains unknown whether an open chromatin is necessary for the differentiation potential of stem cells, and which molecules are needed to maintain open chromatin. Here we show that the chromatin remodelling factor Chd1 is required to maintain the open chromatin of pluripotent mouse embryonic stem cells. Chd1 is a euchromatin protein that associates with the promoters of active genes, and downregulation of Chd1 leads to accumulation of heterochromatin. Chd1-deficient embryonic stem cells are no longer pluripotent, because they are incapable of giving rise to primitive endoderm and have a high propensity for neural differentiation. Furthermore, Chd1 is required for efficient reprogramming of fibroblasts to the pluripotent stem cell state. Our results indicate that Chd1 is essential for open chromatin and pluripotency of embryonic stem cells, and for somatic cell reprogramming to the pluripotent state. PMID: 19587682 [PubMed - indexed for MEDLINE] |
| Cdx genes, inflammation and the pathogenesis of Barrett's metaplasia.
September 15, 2009 at 7:17 am
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| | Cdx genes, inflammation and the pathogenesis of Barrett's metaplasia. Trends Mol Med. 2009 Jul;15(7):313-22 Authors: Colleypriest BJ, Palmer RM, Ward SG, Tosh D Metaplasia is the conversion of one cell or tissue type to another and can predispose patients to neoplasia. Perhaps one of the best-known examples of metaplasia is Barrett's metaplasia (BM), a pathological condition in which the distal oesophageal epithelium switches from stratified squamous to intestinal-type columnar epithelium. BM predisposes to oesophageal adenocarcinoma and is the consequence of long-term acid bile reflux. The incidence of BM and oesophageal adenocarcinoma has risen dramatically in recent years. A key event in the pathogenesis of BM is the induction of oesophageal CDX2 expression. Importantly, recent data reveal the molecular mechanisms that link inflammation in the development of Barrett's metaplasia, CDX2 and the progression to cancer. This review highlights the relationship between inflammation, metaplasia and carcinogenesis. PMID: 19564133 [PubMed - indexed for MEDLINE] |
| Establishment and characterization of a novel untransfected corneal endothelial cell line from New Zealand white rabbits.
September 15, 2009 at 7:17 am
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| | Establishment and characterization of a novel untransfected corneal endothelial cell line from New Zealand white rabbits. Mol Vis. 2009;15:1070-8 Authors: Fan T, Wang D, Zhao J, Wang J, Fu Y, Guo R PURPOSE: To establish and characterize a novel untransfected corneal endothelial cell line from New Zealand white rabbits (NRCE cell line) for studies on corneal endothelial cells. METHODS: Primary culture was initiated with a pure population of NRCE cells from corneal endothelia by successive detachment and reattachment procedure of different durations, and cultured in 20% fetal bovine serum-containing DMEM/F12 media with several supplements. The cell line was characterized by chromosome analysis, fluorescence immunoassay and reverse transcription PCR. The tumorigenic potency of the cell line was examined by subcutaneous inoculation to nude mice. The biocompatibility of the cell line to denuded amnions was examined with routine microscopic and electron microscopic techniques. RESULTS: NRCE cells in primary culture proliferated to confluency in 25 days and has been subcultured to passage 227 to date. The novel NRCE cell line, with a steady growing rate in 20% bovine calf serum (BCS)-containing DMEM/F12 medium and a population doubling time of 40.32 h at passage 191, has been established. NRCE cells exhibited chromosomal aneuploidy but their modal chromosome number was still 44. The results of gene expression patterns of marker proteins and membrane transport proteins, combined with immunofluorescent localization patterns of cell junction proteins, indicated that NRCE cells retained normal corneal endothelial characteristics and normal expression pattern of functional proteins. Furthermore, these cells, without any tumorigenic potency, had excellent biocompatibility to denuded amnions in 20% BCS-containing DMEM/F12 medium, and formed confluent cell sheets attached tightly to denuded amnions. CONCLUSIONS: These results suggest that a novel untransfected NRCE cell line established here maintains normal corneal endothelial characteristics and potencies to form normal cell junctions and perform normal functions of transmembrane transport. PMID: 19503740 [PubMed - indexed for MEDLINE] |
| Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis.
September 15, 2009 at 7:17 am
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| | Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia. 2009 Aug 15;57(11):1192-203 Authors: Bai L, Lennon DP, Eaton V, Maier K, Caplan AI, Miller SD, Miller RH Cell-based therapies are attractive approaches to promote myelin repair. Recent studies demonstrated a reduction in disease burden in mice with experimental allergic encephalomyelitis (EAE) treated with mouse mesenchymal stem cells (MSCs). Here, we demonstrated human bone marrow-derived MSCs (BM-hMSCs) promote functional recovery in both chronic and relapsing-remitting models of mouse EAE, traced their migration into the injured CNS and assayed their ability to modulate disease progression and the host immune response. Injected BM-hMSCs accumulated in the CNS, reduced the extent of damage and increased oligodendrocyte lineage cells in lesion areas. The increase in oligodendrocytes in lesions may reflect BM-hMSC-induced changes in neural fate determination, since neurospheres from treated animals gave rise to more oligodendrocytes and less astrocytes than nontreated neurospheres. Host immune responses were also influenced by BM-hMSCs. Inflammatory T-cells including interferon gamma producing Th1 cells and IL-17 producing Th17 inflammatory cells and their associated cytokines were reduced along with concomitant increases in IL-4 producing Th2 cells and anti-inflammatory cytokines. Together, these data suggest that the BM-hMSCs represent a viable option for therapeutic approaches. PMID: 19191336 [PubMed - indexed for MEDLINE] | | | 
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