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Biomedical subjects

S Shi

Publications and source records attributed to S Shi.

At least 19 recordsLinked to original sources
PubMed2006

Ovine periodontal ligament stem cells: isolation, characterization, and differentiation potential.

Periodontal disease leads to destruction of the connective tissues responsible for restraining teeth within the jaw. To date, various conventional therapies for periodontal regeneration have shown limited and variable clinical outcomes. Recent studies have suggested that newly identified human periodontal ligament stem cells (PDLSCs) may offer an alternate and more reliable strategy for the treatment of periodontal disease using a cell-based tissue engineering approach. In the present study, we generated enriched preparations of PDLSCs derived from ovine periodontal ligament using immunomagnetic bead selection, based on expression of the mesenchymal stem cell-associated antigen CD106 (vascular cell adhesion molecule 1). These CD106+ ovine PDLSCs demonstrated the capacity to form adherent clonogenic clusters of fibroblast-like cells when plated at low densities in vitro. Ex vivo-expanded ovine PDLSCs exhibited a high proliferation rate in vitro and expressed a phenotype (CD44+, CD166+, CBFA-1+, collagen-I+, bone sialoprotein+) consistent with human-derived PDLSCs. Furthermore, cultured ovine PDLSCs expressed high transcript levels of the ligament/tendon-specific early transcription factor scleraxis. Importantly, ex vivo-expanded ovine PDLSCs demonstrated the capacity to regenerate both cementum-like mineral and periodontal ligament when transplanted into NOD/SCID mice. The results from the present study suggest that ovine PDLSCs may potentially be used as a novel cellular therapy to facilitate successful and more predictable regeneration of periodontal tissue using an ovine preclinical model of periodontal disease as a prelude to human clinical studies.

Adult Stem Cells↗
PubMed2006

Essential role of Ca2+ release channels in angiotensin II-induced Ca2+ oscillations and mesangial cell contraction.

The increased resistance of the glomerulus as a result of contractile dysfunction of mesangial cells (MCs) is associated with reduction of glomerular filtration rate and development of glomerulosclerosis. Evidences show MCs contraction changes with intracellular Ca(2+) concentration ([Ca(2+)](i)). Here, we explore the mechanism of angiotensin II (AngII)-induced Ca(2+) oscillations and MCs contraction. Primary MCs from 3-month-old and 28-month-old rats were used for detection of Ca(2+) oscillations and MC planar area with confocal microscopy. AngII could induce typical Ca(2+) oscillations and contraction of MCs. This process was abolished by thapsigargin, 2-aminoethoxydiphenyl borate, or 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine, and partially inhibited by ryanodine, but could not be inhibited in the absence of extracellular Ca(2+). Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate (InsP(3)) receptors displayed a strong colocalization, which may contribute to the amplification of Ca(2+) response. MLC(20) phosphorylation and MC planar area were associated with AngII-induced Ca(2+) oscillations. The frequency of Ca(2+) oscillations was dependent on the AngII concentration and correlated with the MCs' contractive extent, which could be attenuated by KN-93. The amplitude reduction of oscillations correlated with the decrease in aging-related contraction. In conclusion, [Ca(2+)](i) response of MCs to AngII is characterized by repetitive spikes through the following repetitive cycles: Ca(2+) release by phospholipase C -InsP(3) pathway, Ca(2+) amplification by Ca(2+)-activated RyRs and Ca(2+) reuptake by the endoplasmic reticulum. MCs contraction can be modulated by oscillations not only in an AngII-induced frequency-dependent mode but also in an aging-related, amplitude-dependent mode.

Angiotensin II↗
PubMed2006

Enhanced magnetic properties of self-assembled FePt nanoparticles with MnO shell.

Self-assembled FePt/MnO nanoparticles with different morphology and size were synthesized with a polyol process. With the MnO coating, FePt nanoparticles exhibit a high blocking temperature and magnetic moment. The low-temperature hysteresis loop of FePt nanoparticles can be shifted through the AFM pinning of the MnO shell. The aggregation of FePt nanoparticles during the L10 phase transformation can be significantly decreased by coating with the MnO shell.

Iron↗
PubMed2006

Stem cells in the periodontal ligament.

The ability to identify and manipulate stem cells has been a significant advancement in regenerative medicine and has contributed to the development of tissue engineering-based clinical therapies. Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques such as tissue engineering need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. One of the critical requirements for a tissue engineering approach is the delivery of ex vivo expanded progenitor populations or the mobilization of endogenous progenitor cells capable of proliferating and differentiating into the required tissues. By definition, stem cells fulfill these requirements and the recent identification of stem cells within the periodontal ligament represents a significant development in the progress toward predictable periodontal regeneration. In order to explore the importance of stem cells in periodontal wound healing and regeneration, this review will examine contemporary concepts in stem cell biology, the role of periodontal ligament progenitor cells in the regenerative process, recent developments in identifying periodontal stem cells and the clinical implications of these findings.

Animals↗
PubMed2006

Bone marrow-derived mesenchymal stem cells for regenerative medicine in craniofacial region.

The craniofacial region contains many specified tissues including bone, cartilage, muscle, blood vessels and neurons. Defect or dysfunction of the craniofacial tissue after post-cancer ablative surgery, trauma, congenital malformations and progressive deforming skeletal diseases has a huge influence on the patient's life. Therefore, functional reconstruction of damaged tissues is highly expected. Bone marrow-derived mesenchymal stem cells (BMMSCs) are one of the most well characterized postnatal stem cell populations, and considered to be utilized for cell-based clinical therapies. Here, the current understanding and the potential applications in craniofacial tissue regeneration of BMMSCs are reviewed, and the current limitations and drawbacks are also discussed.

Animals↗
PubMed2006

Craniofacial tissue engineering by stem cells.

Craniofacial tissue engineering promises the regeneration or de novo formation of dental, oral, and craniofacial structures lost to congenital anomalies, trauma, and diseases. Virtually all craniofacial structures are derivatives of mesenchymal cells. Mesenchymal stem cells are the offspring of mesenchymal cells following asymmetrical division, and reside in various craniofacial structures in the adult. Cells with characteristics of adult stem cells have been isolated from the dental pulp, the deciduous tooth, and the periodontium. Several craniofacial structures--such as the mandibular condyle, calvarial bone, cranial suture, and subcutaneous adipose tissue--have been engineered from mesenchymal stem cells, growth factor, and/or gene therapy approaches. As a departure from the reliance of current clinical practice on durable materials such as amalgam, composites, and metallic alloys, biological therapies utilize mesenchymal stem cells, delivered or internally recruited, to generate craniofacial structures in temporary scaffolding biomaterials. Craniofacial tissue engineering is likely to be realized in the foreseeable future, and represents an opportunity that dentistry cannot afford to miss.

Absorbable Implants↗
PubMed2005

The efficacy of mesenchymal stem cells to regenerate and repair dental structures.

OBJECTIVES: Identification, characterization, and potential application of mesenchymal stem cells (MSC) derived from human dental tissues. METHODS: Dental pulp and periodontal ligament were obtained from normal human impacted third molars. The tissues were digested in collagenase/dispase to generate single cell suspensions. Cells were cultured in alpha-MEM supplemented with 20% fetal bovine serum, 2 mM l-glutamine, 100 microM l-ascorbate-2-phosphate. Magnetic and fluorescence activated cell sorting were employed to characterize the phenotype of freshly isolated and ex vivo expanded cell populations. The developmental potential of cultured cells was assessed following co-transplantation with hydroxyapetite/tricalcium phosphate (HA/TCP) particles into immunocompromised mice for 8 weeks. RESULTS: MSC were identified in adult human dental pulp (dental pulp stem cells, DPSC), human primary teeth (stem cells from human exfoliated deciduous teeth, SHED), and periodontal ligament (periodontal ligament stem cells, PDLSC) by their capacity to generate clongenic cell clusters in culture. Ex vivo expanded DPSC, SHED, and PDLSC populations expressed a heterogeneous assortment of makers associated with MSC, dentin, bone, smooth muscle, neural tissue, and endothelium. PDLSC were also found to express the tendon specific marker, Scleraxis. Xenogeneic transplants containing HA/TCP with either DPSC or SHED generated donor-derived dentin-pulp-like tissues with distinct odontoblast layers lining the mineralized dentin-matrix. In parallel studies, PDLSC generated cementum-like structures associated with PDL-like connective tissue when transplanted with HA/TCP into immunocompromised mice. CONCLUSION: Collectively, these data revealed the presence of distinct MSC populations associated with dental structures with the potential of stem cells to regenerate living human dental tissues in vivo.

Animals↗
PubMed2005

Recovery of stem cells from cryopreserved periodontal ligament.

Human post-natal stem cells possess a great potential to be utilized in stem-cell-mediated clinical therapies and tissue engineering. It is not known whether cryopreserved human tissues contain functional post-natal stem cells. In this study, we utilized human periodontal ligament to test the hypothesis that cryopreserved human periodontal ligament contains retrievable post-natal stem cells. These cryopreserved periodontal ligament stem cells maintained normal periodontal ligament stem cell characteristics, including expression of the mesenchymal stem cell surface molecule STRO-1, single-colony-strain generation, multipotential differentiation, cementum/periodontal-ligament-like tissue regeneration, and a normal diploid karyotype. Collectively, this study provides valuable evidence demonstrating a practical approach to the preservation of solid-frozen human tissues for subsequent post-natal stem cell isolation and tissue regeneration. The present study demonstrates that human post-natal stem cells can be recovered from cryopreserved human periodontal ligament, thereby providing a practical clinical approach for the utilization of frozen tissues for stem cell isolation.

Adult↗
PubMed2005

NF-kappaB activation in human dental pulp stem cells by TNF and LPS.

Post-natal human dental pulp stem cells (DPSCs) represent a unique precursor population in the dental pulp, which has multipotential and can regenerate a dentin/pulp-like structure. Because the dental pulp is frequently infected by oral bacteria due to dental decay, in this study, we examined whether lipopolysaccharide (LPS) and tumor necrosis factor (TNF) activated the immunologic transcription factor nuclear factor kappa B (NF-kappaB) in DPSCs. We found that both TNF and LPS activated the I-kappa B kinase complex (IKK) in DPSCs to induce the phosphorylation and degradation of IkappaBalpha, resulting in the nuclear translocation of NF-kappaB. Consistently, both TNF and LPS rapidly induced the expression of the NF-kappaB-dependent gene interleukin-8 (IL-8). However, unlike in monocytes, we found that LPS could not induce the phosphorylation of the NF-kappaB active subunit p65 in DPSCs. In summary, our studies suggest that DPSCs may be involved in immune responses during pulpal infection through activating NF-kappaB.

Blotting, Northern↗
PubMed2004

Tsunami hazards in Europe.

Tsunami represents one of the most potentially serious forms of coastal flood risk. Although much is known on the recorded history of tsunamis for given areas of the world, very little information is available on the occurrence of palaeotsunamis during prehistory. This is of fundamental importance in calculating tsunami flood risk for any given coastal area. Given sufficient information on past tsunami activity for a particular coastal area, the numerical calculation of aggregate coastal flood risk (including tsunami) for a coastal area is very difficult to estimate since one needs also to take into account the risk of a tsunami and a storm surge taking place simultaneously during a high tide. Estimates of coastal flood risk also need to consider future changes in relative sea level caused by the combined effects of global climate change and vertical movements of the lithosphere.

Disasters↗
PubMed2003

Comparison of stem-cell-mediated osteogenesis and dentinogenesis.

The difference between stem-cell-mediated bone and dentin regeneration is not yet well-understood. Here we use an in vivo stem cell transplantation system to investigate differential regulation mechanisms of bone marrow stromal stem cells (BMSSCs) and dental pulp stem cells (DPSCs). Elevated expression of basic fibroblast growth factor (bFGF) and matrix metalloproteinase 9 (MMP-9, gelatinase B) was found to be associated with the formation of hematopoietic marrow in BMSSC transplants, but not in the connective tissue of DPSC transplants. The expression of dentin sialoprotein (DSP) specifically marked dentin synthesis in DPSC transplants. Moreover, DPSCs were found to be able to generate reparative dentin-like tissue on the surface of human dentin in vivo. This study provided direct evidence to suggest that osteogenesis and dentinogenesis mediated by BMSSCs and DPSCs, respectively, may be regulated by distinct mechanisms, leading to the different organization of the mineralized and non-mineralized tissues.

Adult↗
PubMed2002

Stem cell properties of human dental pulp stem cells.

In this study, we characterized the self-renewal capability, multi-lineage differentiation capacity, and clonogenic efficiency of human dental pulp stem cells (DPSCs). DPSCs were capable of forming ectopic dentin and associated pulp tissue in vivo. Stromal-like cells were reestablished in culture from primary DPSC transplants and re-transplanted into immunocompromised mice to generate a dentin-pulp-like tissue, demonstrating their self-renewal capability. DPSCs were also found to be capable of differentiating into adipocytes and neural-like cells. The odontogenic potential of 12 individual single-colony-derived DPSC strains was determined. Two-thirds of the single-colony-derived DPSC strains generated abundant ectopic dentin in vivo, while only a limited amount of dentin was detected in the remaining one-third. These results indicate that single-colony-derived DPSC strains differ from each other with respect to their rate of odontogenesis. Taken together, these results demonstrate that DPSCs possess stem-cell-like qualities, including self-renewal capability and multi-lineage differentiation.

Acid Phosphatase↗
PubMed2001

Role of Src kinase in diperoxovanadate-mediated activation of phospholipase D in endothelial cells.

We have shown earlier that oxidant-induced activation of phospholipase D (PLD) in vascular endothelial cells (ECs) is regulated by protein tyrosine kinases. To further understand the regulation of oxidant-induced PLD activation, we investigated the role of Src kinase. Treatment of bovine pulmonary artery ECs (BPAECs) with a model oxidant, diperoxovanadate (DPV), at 5 microM concentration, for 30 min, stimulated PLD activity (four- to eightfold), which was attenuated by tyrosine kinase inhibitors and by Src kinase-specific inhibitors PP-1 and PP-2, in a dose- and time-dependent fashion. Furthermore, BPAECs exposed to DPV (5 microM) for 2 min showed activation of Src kinase as observed by increased tyrosine phosphorylation and autophosphorylation in Src immunoprecipitates, which was attenuated by PP-2. Src immunoprecipitates of cell lysates from control BPAECs exhibited PLD activity in cell-free preparations, which was Arf- and Rho-sensitive and was enhanced at 2 min of DPV (5 microM) treatment. Also, Western blots of Src immunoprecipitates of control cells revealed the presence of PLD(1) and PLD(2), suggesting the association of PLD with Src kinase under basal conditions. However, exposure of cells to DPV (5 microM) for 2 min enhanced the association of PLD(2) but not PLD(1) with Src. Western blotting of immunoprecipitates of PLD(1) and PLD(2) isoforms of control BPAECs revealed the presence of Src under basal conditions and exposure of cells to DPV (5 microM) for 2 min enhanced the association of PLD(2) with Src in PLD(2) immunoprecipitates. Transient expression of a dominant negative mutant of Src in BPAECs attenuated DPV- but not TPA-induced PLD activation. In cell-free preparations, Src did not phosphorylate either PLD(1) or PLD(2) compared to protein kinase Calpha or p38 mitogen-activated protein kinase. These data show for the first time a direct association of Src with PLD in ECs and regulation of PLD in intact cells.

Animals↗
PubMed2001

Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase.

Macrophage activation determines the outcome of infection by Mycobacterium tuberculosis (Mtb). Interferon-gamma (IFN-gamma) activates macrophages by driving Janus tyrosine kinase (JAK)/signal transducer and activator of transcription-dependent induction of transcription and PKR-dependent suppression of translation. Microarray-based experiments reported here enlarge this picture. Exposure to IFN-gamma and/or Mtb led to altered expression of 25% of the monitored genome in macrophages. The number of genes suppressed by IFN-gamma exceeded the number of genes induced, and much of the suppression was transcriptional. Five times as many genes related to immunity and inflammation were induced than suppressed. Mtb mimicked or synergized with IFN-gamma more than antagonized its actions. Phagocytosis of nonviable Mtb or polystyrene beads affected many genes, but the transcriptional signature of macrophages infected with viable Mtb was distinct. Studies involving macrophages deficient in inducible nitric oxide synthase and/or phagocyte oxidase revealed that these two antimicrobial enzymes help orchestrate the profound transcriptional remodeling that underlies macrophage activation.

Animals↗
PubMed2001

Identification of alkylidene hydrazides as glucagon receptor antagonists.

High throughput screening of our small molecule combinatorial library identified a class of benzoylnaphthalenehydrazones with modest affinity for the human glucagon receptor. Optimization of this initial hit through a series of targeted libraries and traditional medicinal chemistry led to ligands with nanomolar affinities. Pharmacological evaluation demonstrated that these ligands were competitive glucagon receptor antagonists. Intravenous administration of a representative benzoylnaphthalenehydrazone into rats attenuated glucagon-stimulated glucose levels.

Animals↗
PubMed2001

Modification of epidermal growth factor-like repeats with O-fucose. Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase.

The O-fucose modification is found on epidermal growth factor-like repeats of a number of cell surface and secreted proteins. O-Fucose glycans play important roles in ligand-induced receptor signaling. For example, elongation of O-fucose on Notch by the beta1,3-N-acetylglucosaminyltransferase Fringe modulates the ability of Notch to respond to its ligands. The enzyme that adds O-fucose to epidermal growth factor-like repeats, GDP-fucose protein O-fucosyltransferase (O-FucT-1), was purified previously from Chinese hamster ovary (CHO) cells. Here we report the isolation of a cDNA that encodes human O-FucT-1. A probe deduced from N-terminal sequence analysis of purified CHO O-FucT-1 was used to screen a human heart cDNA library and expressed sequence tag and genomic data bases. The cDNA contains an open reading frame encoding a protein of 388 amino acids with a predicted N-terminal transmembrane sequence typical of a type II membrane orientation. Likewise, the mouse homolog obtained from an expressed sequence tag and 5'-rapid amplification of cDNA ends of a mouse liver cDNA library encodes a type II transmembrane protein of 393 amino acids with 90.4% identity to human O-FucT-1. Homologs were also found in Drosophila and Caenorhabditis elegans with 41.2 and 29.4% identity to human O-FucT-1, respectively. The human gene (POFUT1) is on chromosome 20 between PLAGL2 and KIF3B, near the centromere at 20p11. The mouse gene (Pofut1) maps near Plagl2 on a homologous region of mouse chromosome 2. POFUT1 gene transcripts were expressed in all tissues examined, consistent with the widespread localization of the modification. Expression of a soluble form of human O-FucT-1 in insect cells yielded a protein of the predicted molecular weight with O-FucT-1 kinetic and enzymatic properties similar to those of O-FucT-1 purified from CHO cells. The identification of the gene encoding protein O-fucosyltransferase I now makes possible mutational strategies to examine the functions of the unusual O-fucose post-translational modification.

Amino Acid Sequence↗