Tuesday, October 27, 2009

10/28 TE-RegenMed-StemCell feed

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Advisory
October 27, 2009 at 8:43 pm

If you are having difficulty hearing the audiocast of the meeting of the CIRM board, so are we. We are told that they are working on improving the quality.

Trounson's Report to Directors Posted by CIRM
October 27, 2009 at 7:55 pm

The California stem cell agency has posted the slides that its president, Alan Trounson, will use to brief directors this afternoon on the state of CIRM.They include his assessment and summary of recent stem cell research worldwide, his priorities and upcoming rounds for new grants. Also on tap is a briefing by Geoff Lomax, senior officer for medical and ethical standards, on CIRM's Compliance

Brighter Financial Outlook for CIRM
October 27, 2009 at 7:37 pm

The California stem cell agency began 2009 with an alarming and surprising report about its financial condition. Today the picture is much brighter.John Robson, vice president for CIRM operations, is scheduled to brief the agency's directors this afternoon about the current state of CIRM finances.His best news will be about the $118 million CIRM received from the recent California bond sale. The

Coverage Advisory
October 27, 2009 at 6:32 pm

Assuming all goes with our Internet connection here in Mazatlan, we will bring you coverage this afternoon and evening of today's meeting of the board of directors of the California Institute for Regenerative Medicine, otherwise known as the the California stem cell agency. The main order of business tonight is discussion and possible action on $167 million in disease team research. The meeting

Endocrine Society calls for expanded scope and funding for stem cell research
October 27, 2009 at 12:57 pm


International Stem Cell Corporation and Reproductive Medicine Associates of New York Announce Breakthrough in Creating an Abundant and Ethical New Source of Human Pluripotent Stem Cells
October 27, 2009 at 8:56 am


Epithelial differentiation of adipose-derived stem cells for laryngeal tissue engineering.
October 27, 2009 at 7:02 am

Related Articles

Epithelial differentiation of adipose-derived stem cells for laryngeal tissue engineering.

Laryngoscope. 2009 Oct 23;

Authors: Long JL, Zuk P, Berke GS, Chhetri DK

OBJECTIVES/HYPOTHESIS:: One potential treatment option for severe vocal fold scarring is to replace the vocal fold cover layer with a tissue-engineered structure containing autologous cells. As a first step toward that goal, we sought to develop a three-dimensional cell-populated matrix resembling the vocal fold layers of lamina propria and epithelium. STUDY DESIGN:: Basic science investigation. METHODS:: Adipose-derived stem cells were cultured in fibrin hydrogels with various growth factors. At the end of the culture period, matrices were sectioned and labeled with immunomarkers to identify cell phenotype. RESULTS:: Adipose-derived stem cells survived, attached, and populated three-dimensional fibrin matrices. Under select conditions, a superficial layer of cells expressing epithelial marker proteins overlay a deeper mesenchymal cell layer. CONCLUSIONS:: A three-dimensional structure of fibrin and adipose-derived stem cells was created as a prototype vocal fold replacement. Two segregated cell phenotypes occurred, producing a bilayered structure resembling epithelium over lamina propria. This preliminary work demonstrates the feasibility of tissue engineering to produce structures for vocal fold replacement. Laryngoscope, 2009.

PMID: 19856398 [PubMed - as supplied by publisher]


The photodynamic effect of tetra-substituted N-methyl-pyridyl-porphine combined with the action of vancomycin or host defense mechanisms disrupts Staphylococcus epidermidis biofilms.
October 27, 2009 at 7:02 am

Related Articles

The photodynamic effect of tetra-substituted N-methyl-pyridyl-porphine combined with the action of vancomycin or host defense mechanisms disrupts Staphylococcus epidermidis biofilms.

Int J Artif Organs. 2009 Oct 24;

Authors: Sbarra MS, Arciola CR, Di Poto A, Saino E, Rohde H, Speziale P, Visai L

The skin commensal and opportunistic pathogen Staphylococcus epidermidis is an important cause of nosocomial infections. Virulence is attributable to formation of biofilm, which provides a microenvironment that protects the bacterium from attack by the host immune system and by chemotherapy. In this study we extended to S. epidermidis strategies previously aimed at treatment of S. aureus biofilms using photodynamic treatment (PDT) combined with chemotherapy or phagocytosis. A significant reduction in bacterial survival was observed when structurally distinct biofilms were exposed to the cationic porphyrin, tetra-substituted N-methyl-pyridyl-porphine (TMP), and simultaneously to visible light. Of note, the extent of biofilm clearance depended on its maturation stage: developing, young biofilms, were more sensitive towards PDT than mature biofilms. Furthermore, PDT-treated biofilms exposed to vancomycin or subjected to phagocytic action of whole blood were almost completely eradicated. The data we obtained establish that PDT combined with antibiotics or host defenses may also be a useful approach for the inactivation of S. epidermidis biofilms.

PMID: 19856267 [PubMed - as supplied by publisher]


3D environment on human mesenchymal stem cells differentiation for bone tissue engineering.
October 27, 2009 at 7:02 am

Related Articles

3D environment on human mesenchymal stem cells differentiation for bone tissue engineering.

J Mater Sci Mater Med. 2009 Oct 25;

Authors: Cordonnier T, Layrolle P, Gaillard J, Langonné A, Sensebé L, Rosset P, Sohier J

In this work a novel method was developed to create a three dimensional environment at a cellular level for bone tissue engineering. Biphasic calcium phosphate (BCP) particles of 140-200 mum were used in association with human mesenchymal stem cells (hMSCs). The cells seeded on these particles adhered and proliferated more rapidly in the first day of culture compared to culture on plastic. Analyses of hMSCs cultured without osteogenic factors on BCP particles revealed an abundant extracellular matrix production forming 3-dimensional (3D) hMSCs/BCP particles constructs after few days. Bone morphogenetic 2 (BMP-2), bone sialoprotein (BSP) and ALP gene expression using real time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed that expression profiles were modified by the culture substrate while the addition of osteogenic medium enhanced bone markers expression. These results indicate that BCP particles alone are able to induce an osteoblastic differentiation of hMSCs that might be of interest for bone tissue engineering.

PMID: 19856200 [PubMed - as supplied by publisher]


Fluorescence-activated cell sorting of PCK-26 antigen-positive cells enables selection of ovine esophageal epithelial cells with improved viability on scaffolds for esophagus tissue engineering.
October 27, 2009 at 7:02 am

Related Articles

Fluorescence-activated cell sorting of PCK-26 antigen-positive cells enables selection of ovine esophageal epithelial cells with improved viability on scaffolds for esophagus tissue engineering.

Pediatr Surg Int. 2009 Oct 24;

Authors: Kofler K, Ainoedhofer H, Höllwarth ME, Saxena AK

OBJECTIVE: For esophagus tissue engineering, isolation and proliferation of esophageal epithelial cells (EEC) is a pre-requisite for scaffold seeding to create constructs. The aim of this study was to sort EEC expressing cytokeratin markers and their proliferative subpopulations; also, to investigate the viability of differentiated EEC subpopulations on collagen scaffolds. METHODS: Ovine esophageal epithelial cells (OEECs) from sheep esophagus were analyzed using flow cytometry for pan cytokeratin (PCK-26) and proliferation cell nuclear antigen (PCNA). Using fluorescent-activated cell sorting, OEEC were separated and analyzed for PCNA expression. The OEEC subpopulations were seeded on collagen scaffolds for a week in vitro culture. RESULTS: Proliferation cell nuclear antigen was expressed in >45% of OEEC isolated. In flow cytometry, 30% OEEC were PCK-26 positive which exhibited a high-proliferative capacity of 80%. PCK-26-negative OECC exhibited a low-proliferative capability of 13%. Scanning electron microscopy demonstrated organized attachment and uniform scaffold coverage in PCK-26-positive cells. CONCLUSION: Ovine esophageal epithelial cells can be divided into PCK-26-positive and negative subpopulations. PCK-26-positive OEEC constitute one-third of the isolated cells with high-proliferative capability. Seeding of PCK-26-positive OEEC on collagen scaffolds leads to uniform distribution of cells in vitro. In esophagus, tissue engineering PCK-26-positive OEEC subpopulation is important for optimal construct generation.

PMID: 19855980 [PubMed - as supplied by publisher]


Nanofibrous biologic laminates replicate the form and function of the annulus fibrosus.
October 27, 2009 at 7:02 am

Related Articles

Nanofibrous biologic laminates replicate the form and function of the annulus fibrosus.

Nat Mater. 2009 Oct 25;

Authors: Nerurkar NL, Baker BM, Sen S, Wible EE, Elliott DM, Mauck RL

Successful engineering of load-bearing tissues requires recapitulation of their complex mechanical functions. Given the intimate relationship between function and form, biomimetic materials that replicate anatomic form are of great interest for tissue engineering applications. However, for complex tissues such as the annulus fibrosus, scaffolds have failed to capture their multi-scale structural hierarchy. Consequently, engineered tissues have yet to reach functional equivalence with their native counterparts. Here, we present a novel strategy for annulus fibrosus tissue engineering that replicates this hierarchy with anisotropic nanofibrous laminates seeded with mesenchymal stem cells. These scaffolds directed the deposition of an organized, collagen-rich extracellular matrix that mimicked the angle-ply, multi-lamellar architecture and achieved mechanical parity with native tissue after 10 weeks of in vitro culture. Furthermore, we identified a novel role for inter-lamellar shearing in reinforcing the tensile response of biologic laminates, a mechanism that has not previously been considered for these tissues.

PMID: 19855383 [PubMed - as supplied by publisher]


Cellular Encapsulation in 3D Hydrogels for Tissue Engineering.
October 27, 2009 at 7:02 am

Related Articles

Cellular Encapsulation in 3D Hydrogels for Tissue Engineering.

J Vis Exp. 2009;(32):

Authors: Khetan S, Burdick J

The 3D encapsulation of cells within hydrogels represents an increasingly important and popular technique for culturing cells and towards the development of constructs for tissue engineering. This environment better mimics what cells observe in vivo, compared to standard tissue culture, due to the tissue-like properties and 3D environment. Synthetic polymeric hydrogels are water-swollen networks that can be designed to be stable or to degrade through hydrolysis or proteolysis as new tissue is deposited by encapsulated cells. A wide variety of polymers have been explored for these applications, such as poly(ethylene glycol) and hyaluronic acid. Most commonly, the polymer is functionalized with reactive groups such as methacrylates or acrylates capable of undergoing crosslinking through various mechanisms. In the past decade, much progress has been made in engineering these microenvironments - e.g., via the physical or pendant covalent incorporation of biochemical cues - to improve viability and direct cellular phenotype, including the differentiation of encapsulated stem cells (Burdick et al.). The following methods for the 3D encapsulation of cells have been optimized in our and other laboratories to maximize cytocompatibility and minimize the number of hydrogel processing steps. In the following protocols (see Figure 1 for an illustration of the procedure), it is assumed that functionalized polymers capable of undergoing crosslinking are already in hand; excellent reviews of polymer chemistry as applied to the field of tissue engineering may be found elsewhere (Burdick et al.) and these methods are compatible with a range of polymer types. Further, the Michael-type addition (see Lutolf et al.) and light-initiated free radical (see Elisseeff et al.) mechanisms focused on here constitute only a small portion of the reported crosslinking techniques. Mixed mode crosslinking, in which a portion of reactive groups is first consumed by addition crosslinking and followed by a radical mechanism, is another commonly used and powerful paradigm for directing the phenotype of encapsulated cells (Khetan et al., Salinas et al.).

PMID: 19855372 [PubMed - in process]


Understanding how the crowded interior of cells stabilizes DNA/DNA and DNA/RNA hybrids-in silico predictions and in vitro evidence.
October 27, 2009 at 7:02 am

Related Articles

Understanding how the crowded interior of cells stabilizes DNA/DNA and DNA/RNA hybrids-in silico predictions and in vitro evidence.

Nucleic Acids Res. 2009 Oct 23;

Authors: Harve KS, Lareu R, Rajagopalan R, Raghunath M

Amplification of DNA in vivo occurs in intracellular environments characterized by macromolecular crowding (MMC). In vitro Polymerase-chain-reaction (PCR), however, is non-crowded, requires thermal cycling for melting of DNA strands, primer-template hybridization and enzymatic primer-extension. The temperature-optima for primer-annealing and extension are strikingly disparate which predicts primers to dissociate from template during extension thereby compromising PCR efficiency. We hypothesized that MMC is not only important for the extension phase in vivo but also during PCR by stabilizing nucleotide hybrids. Novel atomistic Molecular Dynamics simulations elucidated that MMC stabilizes hydrogen-bonding between complementary nucleotides. Real-time PCR under MMC confirmed that melting-temperatures of complementary DNA-DNA and DNA-RNA hybrids increased by up to 8 degrees C with high specificity and high duplex-preservation after extension (71% versus 37% non-crowded). MMC enhanced DNA hybrid-helicity, and drove specificity of duplex formation preferring matching versus mismatched sequences, including hair-pin-forming DNA- single-strands.

PMID: 19854935 [PubMed - as supplied by publisher]


The stimulation of angiogenesis and collagen deposition by copper.
October 27, 2009 at 7:02 am

Related Articles

The stimulation of angiogenesis and collagen deposition by copper.

Biomaterials. 2009 Oct 23;

Authors: Gérard C, Bordeleau LJ, Barralet J, Doillon CJ

Copper is known to trigger endothelial cells towards angiogenesis. Different approaches have been investigated to develop vascularisation in biomaterials. The angiogenic and healing potential of copper ions in combination with two major angiogenic factors was examined. A 3D culture system in which, under stimulation by FGF-2 and to a lesser degree with VEGF, endothelial cells assembled into structures resembling to an angiogenic process was used. The combination of CuSO(4) with increasing doses of VEGF or FGF-2 enhanced the complexity of angiogenic networks in a significant manner. In vivo studies were also conducted by incorporating FGF-2 with CuSO(4) in a cylindrical collagen-based scaffold. CuSO(4) enhanced significantly the invasion of microvessel compared to control implants and to 20ng FGF-2+/-CuSO(4). Vascular infiltration was also significantly improved by combination of CuSO(4) with FGF-2, compared to FGF-2 alone (0.2 and 1mug). Nevertheless, in comparison with CuSO(4) alone, there was a significant increase only with 1mug of FGF-2 combined with CuSO(4). Significantly, collagen fiber deposition was enhanced following the combinatory loading in comparison to that with FGF-2 alone but not with CuSO(4) only. Thus, copper associated with growth factors may have synergistic effects which are highly attractive in the fields of tissue engineering (e.g., bone) and biomaterials.

PMID: 19854506 [PubMed - as supplied by publisher]


Re: Michael J. Morris, Daisy Huang, William K. Kelly, et al. Phase 1 Trial of High-Dose Exogenous Testosterone in Patients with Castration-Resistant Metastatic Prostate. Eur Urol 2009;56:237-244.
October 27, 2009 at 7:02 am

Related Articles

Re: Michael J. Morris, Daisy Huang, William K. Kelly, et al. Phase 1 Trial of High-Dose Exogenous Testosterone in Patients with Castration-Resistant Metastatic Prostate. Eur Urol 2009;56:237-244.

Eur Urol. 2009 Oct 20;

Authors: Drewa T, Chlosta P

PMID: 19853990 [PubMed - as supplied by publisher]


Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering.
October 27, 2009 at 7:02 am

Related Articles

Local delivery of a collagen-binding FGF-1 chimera to smooth muscle cells in collagen scaffolds for vascular tissue engineering.

Biomaterials. 2009 Oct 22;

Authors: Pang Y, Wang X, Ucuzian AA, Brey EM, Burgess WH, Jones KJ, Alexander TD, Greisler HP

We investigated the delivery of R136K-CBD (a collagen-binding mutant chimera of fibroblast growth factor-1) with a type I collagen scaffold as the delivery vehicle to smooth muscle cells (SMCs) for vascular tissue engineering. The binding affinity of R136K-CBD to 3-D collagen scaffolds was investigated both in the presence and absence of cells and/or salts. 2-D and 3-D visualization of delivery of R136K-CBD into SMCs were accomplished by combined fluorescent and reflection confocal microscopy. The mitogenic effect of collagen-immobilized R136K-CBD on SMCs in 3-D collagen was studied by Cyquant assay at different time intervals. In the group devoid of salt and cells, no detectable release of R136K-CBD into overlying culture media was found, compared with burst-and-continuous release of R136K and FGF-1 over a 14-day period in all other groups. The release rate of R136K-CBD was 1.7 and 1.6-fold less than R-136K and FGF-1 when media was supplemented with 2m salt (P<0.0001), and 2.6 and 2.5-fold less in cell-populated collagen hydrogels (P<0.0001), respectively. R136K-CBD showed essentially uniform binding to collagen and its distribution was dependent on that of the collagen scaffold. Internalization of R136K-CBD into SMCs was documented by confocal microscopy. 3-D local delivery of collagen-immobilized R136K-CBD increased the proliferation of SMCs in the collagen matrix to significantly greater levels and for a significantly greater duration than R136K or FGF-1, with 2.0 and 2.1-fold more mitogenicity than R136K and FGF-1 respectively (P<0.0001) at day 7. The results suggest that our collagen-binding fusion protein is an effective strategy for growth factor delivery for vascular tissue engineering.

PMID: 19853908 [PubMed - as supplied by publisher]


Extracellular matrix components direct porcine muscle stem cell behaviour.
October 27, 2009 at 7:02 am

Related Articles

Extracellular matrix components direct porcine muscle stem cell behaviour.

Exp Cell Res. 2009 Oct 21;

Authors: Wilschut KJ, Haagsman HP, Roelen BA

In muscle tissue, extracellular matrix proteins, together with the vasculature system, muscle-residence cells and muscle fibres, create the niche for muscle stem cells. The niche is important in controlling proliferation and directing differentiation of muscle stem cells to sustain muscle tissue. Mimicking the extracellular muscle environment improves tools exploring the behaviour of primary muscle cells. Optimizing cell culture conditions to maintain muscle commitment is important in stem cell-based studies concerning toxicology screening, ex vivo skeletal muscle tissue engineering and in enhancement of clinical efficiency. We used the muscle extracellular matrix proteins collagen type I, fibronectin, laminin, and also gelatin and Matrigel as surface coatings of tissue culture plastic to resemble the muscle extracellular matrix. Several important factors that determine myogenic commitment of the primary muscle cells were characterized by quantitative real time RT-PCR and immunofluorescence. Adhesion of high PAX7 expressing satellite cells was improved if the cells were cultured on fibronectin or laminin coatings. Cells cultured on Matrigel and laminin coatings showed dominant integrin expression levels and exhibited an activated Wnt pathway. Under these conditions both stem cell proliferation and myogenic differentiation capacity were superior if compared to cells cultured on collagen type I, fibronectin and gelatin. In conclusion, Matrigel and laminin are the preferred coatings to sustain the proliferation and myogenic differentiation capacity of the primary porcine muscle stem cells, when cells are removed from their natural environment for in vitro culture.

PMID: 19853598 [PubMed - as supplied by publisher]


Myogenic differentiation of human bone marrow mesenchymal stem cells on a 3D nano fibrous scaffold for bladder tissue engineering.
October 27, 2009 at 7:02 am

Related Articles

Myogenic differentiation of human bone marrow mesenchymal stem cells on a 3D nano fibrous scaffold for bladder tissue engineering.

Biomaterials. 2009 Oct 21;

Authors: Tian H, Bharadwaj S, Liu Y, Ma H, Ma PX, Atala A, Zhang Y

Current strategies for engineering bladder tissues include a bladder biopsy for in vitro cell expansion for use in reconstructive procedures. However, this approach cannot be used in patients with bladder cancer who need a complete bladder replacement. Bone marrow mesenchymal stem cells (BMSC) might be an alternative cell source to better meet this need. We investigated the effects of soluble growth factors, bladder extracellular matrix (ECM), and 3D dynamic culture on cell proliferation and differentiation of human BMSC into smooth muscle cells (SMC). Myogenic growth factors (PDGF-BB and TGF-beta1) alone, or combined either with bladder ECM or dynamic cultures, induced BMSC to express smooth muscle-specific genes and proteins. Either ECM or the dynamic culture alone promoted cell proliferation but did not induce myogenic differentiation of BMSC. A highly porous poly-l-lactic acid (PLLA) scaffold provided a 3D structure for maximizing the cell-matrix penetration, maintained myogenic differentiation of the induced BMSC, and promoted tissue remolding with rich capillary formation in vivo. Our results demonstrate that myogenic-differentiated BMSC seeded on a nano fibrous PLLA scaffold can be potentially used for cell-based tissue engineering for bladder cancer patients requiring cystoplasty.

PMID: 19853294 [PubMed - as supplied by publisher]


Modified PHBV scaffolds by in-situ UV polymerization: structural characteristic, mechanical properties and BMSCs compatibility.
October 27, 2009 at 7:02 am

Related Articles

Modified PHBV scaffolds by in-situ UV polymerization: structural characteristic, mechanical properties and BMSCs compatibility.

Acta Biomater. 2009 Oct 20;

Authors: Ke Y, Wang Y, Ren L, Zhao Q, Huang W

An ideal scaffold provides an interface for cell adhesion and maintains enough biomechanical support during tissue regeneration. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) scaffolds of pore sizes ranging from 100 to 500 mum and of porosity about 90% were prepared by particulate leaching method, and then modified by introducing polyacrylamide (PAM) on the inner surface of scaffolds using in-situ UV polymerization, with the aim to enhance the biological and mechanical properties of the PHBV scaffolds. The modified PHBV scaffolds had interconnected pores with porosity of 75.4-78.6% and pore sizes at peak volume from 20 to 50 mum. The compressive load and modulus were up to 62.45 N and 1.06 MPa, respectively. Water swelling percentage (WSP) of the modified PHBV scaffolds increased notably compared with that of the PHBV scaffolds, with the maximum WSP at 537%. Sheep bone mesenchymal stem cells (BMSCs) were cultured on the PHBV and modified PHBV. The hydrophilic PAM chains did not influence BMSCs viability and proliferation index, however, the initial cell adhesion at 1 h of culture enhanced significantly. Framing PHBV scaffold along with gel-like PAM chains inside is a novel model of inner surface modification for PHBV scaffolds, which shows potentiality in tissue engineering application.

PMID: 19853067 [PubMed - as supplied by publisher]


Biodegradable Fibrous Scaffolds with Diverse Properties by Electrospinning Candidates from a Combinatorial Macromer Library.
October 27, 2009 at 7:02 am

Related Articles

Biodegradable Fibrous Scaffolds with Diverse Properties by Electrospinning Candidates from a Combinatorial Macromer Library.

Acta Biomater. 2009 Oct 20;

Authors: Metter RB, Ifkovits JL, Hou K, Vincent L, Hsu B, Wang L, Mauck RL, Burdick JA

The properties of electrospun fibrous scaffolds, including degradation, mechanics and cellular interactions, are important for their use in tissue engineering applications. Although some diversity has been obtained previously in fibrous scaffolds, optimization of scaffold properties relies on iterative techniques in both polymer synthesis and processing. Here, we electrospun candidates from a combinatorial library of biodegradable and photopolymerizable poly(beta-amino ester)s (PBAEs) to show that the diversity in properties found in this library is retained when processed into fibrous scaffolds. Specifically, three PBAE macromers were electrospun into scaffolds and possessed similar initial mechanical properties, but exhibited mass loss ranging from rapid (complete degradation within approximately 2 weeks) to moderate (complete degradation within approximately 3 months) to slow (only partial degradation after 3 months). These trends in mechanics and degradation mimicked what was previously observed in the bulk polymers. Although cellular adhesion was dependent on the polymer composition in films, adhesion to scaffolds that were electrospun with gelatin was similar on all formulations and controls. To further illustrate the diverse properties that are attainable in these systems, the fastest and slowest degrading polymers were electrospun together into one scaffold, but as distinct fiber populations. This dual-polymer scaffold exhibited behavior in mass loss and mechanics with time that fell between the single-polymer scaffolds. In general, this work indicates that combinatorial libraries may be an important source of information and specific polymer compositions for the fabrication of electrospun fibrous scaffolds with tunable properties.

PMID: 19853066 [PubMed - as supplied by publisher]


Nanoparticles for direct nose-to-brain delivery of drugs.
October 27, 2009 at 7:02 am

Related Articles

Nanoparticles for direct nose-to-brain delivery of drugs.

Int J Pharm. 2009 Sep 8;379(1):146-57

Authors: Mistry A, Stolnik S, Illum L

This review aims to evaluate the evidence for the existence of a direct nose-to-brain delivery route for nanoparticles administered to the nasal cavity and transported via the olfactory epithelium and/or via the trigeminal nerves directly to the CNS. This is relevant in the field of drug delivery as well as for new developments in nanotechnology. Experiments in animal models have shown that nano-sized drug delivery systems can enhance nose-to-brain delivery of drugs compared to equivalent drug solutions formulations. Protection of the drug from degradation and/or efflux back into the nasal cavity may partly be the reason for this effect of nanoparticles. It is uncertain, however, whether drug from the nanoparticles is being released in the nasal cavity or the nanoparticles carrying the drug are transported via the olfactory system or the trigeminal nerves into the CNS where the drug is released. Furthermore, toxicity of nanoparticulate drug delivery systems in the nasal cavity and/or in the CNS has not been extensively studied and needs to be considered carefully.

PMID: 19555750 [PubMed - indexed for MEDLINE]


Re: Udo Nagele, Sabine Maurer, Gerard Feil, et al. In vitro investigations of tissue-engineered multilayered urothelium established from bladder washings. Eur Urol 2008;54:1414-22.
October 27, 2009 at 7:02 am

Related Articles

Re: Udo Nagele, Sabine Maurer, Gerard Feil, et al. In vitro investigations of tissue-engineered multilayered urothelium established from bladder washings. Eur Urol 2008;54:1414-22.

Eur Urol. 2009 May;55(5):e79-80; author reply e81

Authors: Drewa T

PMID: 18945544 [PubMed - indexed for MEDLINE]


The Extracellular Matrix In Development and Morphogenesis: A Dynamic View.
October 27, 2009 at 6:00 am

The Extracellular Matrix In Development and Morphogenesis: A Dynamic View.

Dev Biol. 2009 Oct 22;

Authors: Rozario T, Desimone DW

The extracellular matrix (ECM) is synthesized and secreted by embryonic cells beginning at the earliest stages of development. Our understanding of ECM composition, structure and function has grown considerably in the last several decades and this knowledge has revealed that the extracellular microenvironment is critically important for cell growth, survival, differentiation and morphogenesis. ECM and the cellular receptors that interact with it mediate both physical linkages with the cytoskeleton and the bidirectional flow of information between the extracellular and intracellular compartments. This review considers the range of cell and tissue functions attributed to ECM molecules and summarizes recent findings specific to key developmental processes. The importance of ECM as a dynamic repository for growth factors is highlighted along with more recent studies implicating the 3-dimensional organization and physical properties of the ECM as it relates to cell signaling and the regulation of morphogenetic cell behaviors. Embryonic cell and tissue generated forces and mechanical signals arising from ECM adhesion represent emerging areas of interest in this field.

PMID: 19854168 [PubMed - as supplied by publisher]


Myogenic differentiation of human bone marrow mesenchymal stem cells on a 3D nano fibrous scaffold for bladder tissue engineering.
October 27, 2009 at 6:00 am

Myogenic differentiation of human bone marrow mesenchymal stem cells on a 3D nano fibrous scaffold for bladder tissue engineering.

Biomaterials. 2009 Oct 21;

Authors: Tian H, Bharadwaj S, Liu Y, Ma H, Ma PX, Atala A, Zhang Y

Current strategies for engineering bladder tissues include a bladder biopsy for in vitro cell expansion for use in reconstructive procedures. However, this approach cannot be used in patients with bladder cancer who need a complete bladder replacement. Bone marrow mesenchymal stem cells (BMSC) might be an alternative cell source to better meet this need. We investigated the effects of soluble growth factors, bladder extracellular matrix (ECM), and 3D dynamic culture on cell proliferation and differentiation of human BMSC into smooth muscle cells (SMC). Myogenic growth factors (PDGF-BB and TGF-beta1) alone, or combined either with bladder ECM or dynamic cultures, induced BMSC to express smooth muscle-specific genes and proteins. Either ECM or the dynamic culture alone promoted cell proliferation but did not induce myogenic differentiation of BMSC. A highly porous poly-l-lactic acid (PLLA) scaffold provided a 3D structure for maximizing the cell-matrix penetration, maintained myogenic differentiation of the induced BMSC, and promoted tissue remolding with rich capillary formation in vivo. Our results demonstrate that myogenic-differentiated BMSC seeded on a nano fibrous PLLA scaffold can be potentially used for cell-based tissue engineering for bladder cancer patients requiring cystoplasty.

PMID: 19853294 [PubMed - as supplied by publisher]


Selective Isolation of Young Cells from Human Corneal Endothelium by the Sphere-Forming Assay.
October 27, 2009 at 6:00 am

Selective Isolation of Young Cells from Human Corneal Endothelium by the Sphere-Forming Assay.

Tissue Eng Part C Methods. 2009 Oct 23;

Authors: Mimura T, Yamagami S, Yokoo S, Usui T, Amano S

To investigate whether a representative adult stem cells/precursor cell isolation method (the sphere-forming assay) could isolate cells with differences of telomere length, telomerase activity, and characteristics reflecting senescence. The sphere-forming assay was performed to obtain precursors from cultured sixth passage (P6) human corneal endothelial cells. P6 and P7 cultured corneal endothelial cells were used as the controls. Telomere length, telomerase activity, and senescence-associated factors were evaluated in precursors and controls. Precursors obtained from the spheres had longer telomeres and higher telomerase activity than cultured P6 cells. Strong positive staining for senescence-associated beta-galactosidase activity was detected in P6 and P7 cultured corneal endothelial cells, whereas little or not staining was detected in the precursors within spheres obtained from P6 cultured corneal endothelial cells or their progeny. The progeny of spheres derived from cultured corneal endothelial cells were small regular cells that grew at a higher density and contained more 5-bromo-2'-deoxyuridine-incorporating cells compared with the parental cultured cells. These findings indicate that the sphere-forming assay enriches precursors with longer telomeres, higher telomerase activity, and younger progeny than the original cells. Sphere-forming assay may contribute to obtaining the young cells needed for regenerative medicine.

PMID: 19852617 [PubMed - as supplied by publisher]


Controlling life: from Jacques Loeb to regenerative medicine.
October 27, 2009 at 6:00 am

Controlling life: from Jacques Loeb to regenerative medicine.

J Hist Biol. 2009;42(2):215-30

Authors: Maienschein J

In his 1987 book Controlling Life: Jacques Loeb and the Engineering Ideal in Biology, Philip Pauly presented his readers with the biologist Jacques Loeb and his role in developing an emphasis on control of life processes. Loeb's work on artificial parthenogenesis, for example, provided an example of bioengineering at work. This paper revisits Pauly's study of Loeb and explores the way current research in regenerative medicine reflects the same tradition. A history of regeneration research reveals patterns of thinking and research methods that both echo Loeb's ideology and point the way to modern studies. Pauly's work revealed far more than we readers realized at the time of its publication.

PMID: 19852396 [PubMed - in process]


How the Lucky 11 Made Their Way: A $200 Million Tale
October 27, 2009 at 12:43 am

Seventy-three pilgrims started out on California's disease team trail last March, looking to share $210 million. Only 11 have finished, unless the men and women who control $3 billion decide differently.The initial number of stem cell argonauts was substantially less than predicted by Alan Trounson, president of the California stem cell agency, which is financed by $3 billion borrowed by the

CIRM Board Meeting Available on Internet, $167 Million to be Handed Out
October 26, 2009 at 11:03 pm

This week's board meetings of the California stem cell agency, during which the panel will give away $167 million, can be heard by interested parties via an audiocast on the Internet. The actual public meetings tomorrow and Wednesday will be in Los Angeles with a remote teleconference location at ValleyCare Health Systems in Pleasanton in Northern California. Specific instructions for the
 

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