Saturday, November 7, 2009

11/8 pubmed: "regenerative medici...

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Stem cell technologies for tissue regeneration in dentistry.
November 7, 2009 at 9:28 am

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Stem cell technologies for tissue regeneration in dentistry.

Minerva Stomatol. 2009 Oct;58(10):483-500

Authors: Rimondini L, Mele S

Embryonal and adult stem cells represent a very interesting research field. Mesenchymal stem cells in particular, derived from different sources, in the last ten years have gained more interest because of their high differentiation potential and their availability. They represent a potential key component in autologos graft for tissue regeneration. Cell-therapy based tissue engineering, even in dentistry field, is based on two approaches: the first is the direct implant of cells in tissues and the second involve the use of a scaffold acting both as a template of tissue and as a carrier of cells. Interest in this technologies continues to increase in dental application as a substitute for traditional treatments and artificial components. Nevertheless, few clinical reports of this topic are available. This review will discuss the current challenges in stem cells field, in particular their differentiation toward oral tissues. Bone marrow, adipose tissues, periodontal ligament and pulp will be described as potential sources of stem cells for oral tissue regeneration.

PMID: 19893474 [PubMed - in process]


Matrilysin (Matrix Metalloproteinase-7) Regulates Anti-Inflammatory and Antifibrotic Pulmonary Dendritic Cells That Express CD103 ({alpha}E{beta}7-Integrin).
November 7, 2009 at 9:28 am

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Matrilysin (Matrix Metalloproteinase-7) Regulates Anti-Inflammatory and Antifibrotic Pulmonary Dendritic Cells That Express CD103 ({alpha}E{beta}7-Integrin).

Am J Pathol. 2009 Nov 5;

Authors: Manicone AM, Huizar I, McGuire JK

The E-cadherin receptor CD103 (alphaEbeta7-integrin) is expressed on specific populations of pulmonary dendritic cells (DC) and T cells. However, CD103 function in the lung is not well understood. Matrilysin (MMP-7) expression is increased in lung injury and cleaves E-cadherin from injured lung epithelium. Thus, to assess matrilysin effects on CD103-E-cadherin interactions in lung injury, wild-type, CD103(-/-), and Mmp7(-/-) mice, in which E-cadherin isn't cleaved in the lung, were treated with bleomycin or bleomycin with nFMLP to reverse the defect in acute neutrophil influx seen in Mmp7(-/-) mice. Pulmonary CD103(+) DC were significantly increased in injured wild-type compared with Mmp7(-/-) mice, and CD103(+) leukocytes showed significantly enhanced interaction with E-cadherin on injured wild-type epithelium than with Mmp7(-/-) epithelium in vitro and in vivo. Bleomycin-treated CD103(-/-) mice had persistent neutrophilic inflammation, increased fibrosis, and increased mortality compared with wild-type mice, a phenotype that was partially recapitulated in bleomycin/nFMLP-treated Mmp7(-/-) mice. Soluble E-cadherin increased IL-12 and IL-10 and reduced IL-6 mRNA expression in wild-type bone marrow-derived DC but not in CD103(-/-) bone marrow-derived DC. Similar mRNA patterns were seen in lungs of bleomycin-injured wild-type, but not CD103(-/-) or Mmp7(-/-), mice. In conclusion, matrilysin regulates pulmonary localization of DC that express CD103, and E-cadherin cleavage may activate CD103(+) DC to limit inflammation and inhibit fibrosis.

PMID: 19893044 [PubMed - as supplied by publisher]


Pharmacological Retention of Oral Mucosa Progenitor/Stem Cells.
November 7, 2009 at 9:28 am

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Pharmacological Retention of Oral Mucosa Progenitor/Stem Cells.

J Dent Res. 2009 Nov 5;

Authors: Izumi K, Inoki K, Fujimori Y, Marcelo CL, Feinberg SE

Oral mucosa progenitor/stem cells reside as a small-sized cell population that eventually differentiates concurrently with an increase in cell size. Activation of the mammalian target of rapamycin (mTOR) leads to an increase in cell size. We hypothesized that rapamycin, a specific inhibitor of mTOR, will maintain primary human oral keratinocytes as a small-sized, undifferentiated cell population capable of retaining their proliferative capacity. Primary, rapamycin-treated (2 nM, 20 nM) oral keratinocytes showed a diminished cell size that correlated with a higher clonogenicity, a longer-term proliferative potential, and a slower cycling cell population concurrent with decreased expression of a differentiation marker when compared with untreated cells. Only the 2-nM rapamycin-treated oral keratinocytes maintained their ability to regenerate oral mucosa in vitro after 15 weeks of culture. Rapamycin, a Food and Drug Administration-approved drug, may have applicability for use in creating a highly proliferative cell population for use in regenerative medicine.

PMID: 19892916 [PubMed - as supplied by publisher]


The contribution of plasmid design and release to in vivo gene expression following delivery from cationic polymer modified scaffolds.
November 7, 2009 at 9:28 am

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The contribution of plasmid design and release to in vivo gene expression following delivery from cationic polymer modified scaffolds.

Biomaterials. 2009 Nov 3;

Authors: Avilés MO, Lin CH, Zelivyanskaya M, Graham JG, Boehler RM, Messersmith PB, Shea LD

Tissue engineering scaffolds capable of gene delivery can provide a structure that supports tissue formation while also inducing the expression of inductive factors. Sustained release strategies are hypothesized to maintain elevated plasmid concentrations locally that can enhance gene transfer. In this report, we investigate the relationship between plasmid release kinetics and the extent and duration of transgene expression. Scaffolds were fabricated from polymer microspheres modified with cationic polymers (polyethylenimine, poly(l-lysine), poly(allylamine hydrochloride), polydiallyldimethylammonium) or polydopamine (PD), with PD enhancing incorporation and slowing release. In vivo implantation of scaffolds into the peritoneal fat pad had no significant changes in the level and duration of transgene expression between PD and unmodified scaffolds. Control studies with plasmid dried onto scaffolds, which exhibited a rapid release, and scaffolds with extended leaching to reduce initial quantities released had similar levels and duration of expression. Changing the plasmid design, from a cytomegalovirus (CMV) to an ubiquitin C (UbC) promoter substantially altered the duration of expression. These studies suggest that the initial dose released and vector design affect the extent and duration of transgene expression, which may be sustained over several weeks, potentially leading to numerous applications in cell transplantation and regenerative medicine.

PMID: 19892398 [PubMed - as supplied by publisher]


The Design and Use of Animal Models for Translational Research in Bone Tissue Engineering and Regenerative Medicine.
November 7, 2009 at 9:28 am

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The Design and Use of Animal Models for Translational Research in Bone Tissue Engineering and Regenerative Medicine.

Tissue Eng Part B Rev. 2009 Nov 5;

Authors: Muschler G, Raut VP, Patterson T, Wenke JC, Hollinger JO

This review provides an overview of animal models for the evaluation, comparison and systematic optimization of tissue engineering and regenerative medicine strategies related to bone tissue. This review includes an overview of major factors that influence the rational design and selection of an animal model. A comparison is provided of the 10 mammalian species that are most commonly used in bone research, and existing guidelines and standards are discussed. This review also identifies gaps in the availability of animal models: a) the need for assessment of the predictive value of preclinical models for relative clinical efficacy, b) the need for models that more effectively mimic the wound healing environment and mass transport conditions in the most challenging clinical settings (e.g., bone repair involving large bone and soft tissue defects and sites of prior surgery), and c) the need for models that allow more effective measurement and detection of cell trafficking events and ultimate cell fate during the processes of bone modeling, remodeling and regeneration. The ongoing need for both continued innovation and refinement in animal model systems, and the need and value of more effective standardization is reinforced.

PMID: 19891542 [PubMed - as supplied by publisher]


Facial Reconstruction by Biosurgery: Cell Transplantation vs. Cell Homing.
November 7, 2009 at 9:28 am

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Facial Reconstruction by Biosurgery: Cell Transplantation vs. Cell Homing.

Tissue Eng Part B Rev. 2009 Nov 5;

Authors: Mao J, Stosich MS, Moioli E, Lee CH, Fu S, Bastian B, Eisig S, Zemnick C, Ascherman J, Wu J, Rohde C, Ahn J

The face distinguishes one human being from another. When the face is disfigured from trauma, tumor removal, congenital anomalies or chronic diseases, the patient has a strong desire for functional and esthetic restoration. Current practice of facial reconstruction using autologous grafts, synthetic fillers and prostheses is frequently below the surgeon's and patient's expectations. Facial reconstruction has yet to take advantage of recent advances in seemingly unrelated fields of stem cell biology, chemical engineering, biomaterials and tissue engineering. "Biosurgery", a new concept that we propose, will incorporate novel principles and strategies of bioactive cues, biopolymers and/or cells to restore facial defects. Small facial defects can likely be reconstructed by cell homing and without cell transplantation. A critical advantage of cell homing is that agilely recruited endogenous cells have the potential to harness the host's innate capacity for regeneration, thus accelerating the rate of regulatory and commercialization processes for product development. Large facial defects, however, may not be restorable without cell delivery per our understanding at this time. New breakthrough in biosurgery will likely originate from integrated strategies of cell biology, cytokine biology, chemical engineering, biomaterials and tissue engineering. Regardless of cell homing or cell delivery approaches, biosurgery not only will minimize surgical trauma and repetitive procedures, but also produce long-lasting results. At the same time, caution must be exercised against the development of products that lack scientific basis or dogmatic combination of cells, biomaterials and biomolecules. Together, scientifically derived biosurgery will undoubtedly develop into new technologies that offer increasingly natural reconstruction and/or augmentation of the face.

PMID: 19891541 [PubMed - as supplied by publisher]


Fabrication and Characterization of a Novel Acellular Cartilage Matrix Scaffold for Tissue Engineering.
November 7, 2009 at 9:28 am

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Fabrication and Characterization of a Novel Acellular Cartilage Matrix Scaffold for Tissue Engineering.

Tissue Eng Part C Methods. 2009 Nov 5;

Authors: Yang Z, Shi Y, Wei X, He J, Yang S, Dickson G, Tang J, Xiang J, Song C, Li G

The objectives of this study were to develop a three-dimensional acellular cartilage matrix (ACM) and investigate its possibility for use as a scaffold in cartilage tissue engineering. Bovine articular cartilage was decellularized sequentially with trypsin, nuclease solution, hypotonic buffer and Triton X 100 solution and moulded with freeze-drying process and cross-linked by UV irradiation. Histological and biochemical analysis showed that the ACM was devoid of cells and still maintained the collagen and glycosaminoglycan components of cartilage. Scanning electronic microscopy (SEM) and mercury intrusion porosimetry (MIP) showed that the ACM had a porous sponge-like structure of high porosity. The ACM scaffold had good biocompatibility with cultured rabbit bone marrow mesenchymal stem cells (MSCs) with no indication of cytotoxicity both in contact and in extraction assays. The cartilage defects repair in rabbit knees with the MSCs-ACM constructs had a significant improvement of histological scores than the control groups at 6 and 12 weeks. In summary, the ACM possessed the characteristics which afford it as a potential scaffold for cartilage tissue engineering.

PMID: 19891538 [PubMed - as supplied by publisher]


Gas-in-Liquid Foam Templating as a Method for the Production of Highly Porous Scaffolds.
November 7, 2009 at 9:28 am

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Gas-in-Liquid Foam Templating as a Method for the Production of Highly Porous Scaffolds.

Biomacromolecules. 2009 Nov 6;

Authors: Barbetta A, Gumiero A, Pecci R, Bedini R, Dentini M

In the present work, a novel synthetic methodology for the preparation of scaffold of biopolymeric nature is described. In particular, a porous gelatin scaffold was prepared by foam templating. The gas phase, nitrogen, was generated by means of the reaction between sulfamic acid and sodium nitrite in situ a concentrated solution of gelatin and in the presence of a suitable polymeric surfactant in association with sodium dodecyl sulfate. The foam was prepared at a temperature of 45 degrees C and then let gel at 5 degrees C. After purification, the physical gel was auto-cross-linked with EDC and freeze-dried. The scaffold synthesized with this technique presents a morphology characterized by voids of spherical symmetry highly interconnected by a plurality of interconnects, and, as a consequence, is particularly suited for cell culturing. In more quantitative terms, voids and interconnects are characterized by an average diameter of 230 and 90 mum, respectively. Preliminary tests of cell culturing demonstrated the suitability of such a scaffold for tissue engineering applications.

PMID: 19891500 [PubMed - as supplied by publisher]


Prevascularization of cardiac patch on the omentum improves its therapeutic outcome.
November 7, 2009 at 9:28 am

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Prevascularization of cardiac patch on the omentum improves its therapeutic outcome.

Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14990-5

Authors: Dvir T, Kedem A, Ruvinov E, Levy O, Freeman I, Landa N, Holbova R, Feinberg MS, Dror S, Etzion Y, Leor J, Cohen S

The recent progress made in the bioengineering of cardiac patches offers a new therapeutic modality for regenerating the myocardium after myocardial infarction (MI). We present here a strategy for the engineering of a cardiac patch with mature vasculature by heterotopic transplantation onto the omentum. The patch was constructed by seeding neonatal cardiac cells with a mixture of prosurvival and angiogenic factors into an alginate scaffold capable of factor binding and sustained release. After 48 h in culture, the patch was vascularized for 7 days on the omentum, then explanted and transplanted onto infarcted rat hearts, 7 days after MI induction. When evaluated 28 days later, the vascularized cardiac patch showed structural and electrical integration into host myocardium. Moreover, the vascularized patch induced thicker scars, prevented further dilatation of the chamber and ventricular dysfunction. Thus, our study provides evidence that grafting prevascularized cardiac patch into infarct can improve cardiac function after MI.

PMID: 19706385 [PubMed - indexed for MEDLINE]


A dumbbell-shaped small molecule that promotes cell adhesion and growth.
November 7, 2009 at 9:28 am

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A dumbbell-shaped small molecule that promotes cell adhesion and growth.

Chem Biol. 2009 Jul 31;16(7):773-82

Authors: Yamazoe S, Shimogawa H, Sato S, Esko JD, Uesugi M

During an image-based phenotype screening of our chemical library, we noted a small molecule that boosts the adhesion and growth of human cells. Chemical and cell biological experiments suggest that the diaryldispirotripiperazine derivative (adhesamine) targets selective cell-surface glycosaminoglycans, especially heparan sulfate, for increasing cell adhesion and growth. The addition of adhesamine to the culture medium enables the adhesion of even floating lymphocytes to cell culture plates and the microinjection into them. Unlike poly-L-lysine, adhesamine induces apparently normal cell adhesion accompanied by organized actin structures and activation of focal adhesion kinase and ERK1/2 mitogen-activated protein kinases. Adhesamine may be useful as a cell-attaching reagent for cell engineering and basic cell biology.

PMID: 19635414 [PubMed - indexed for MEDLINE]

 

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