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| California Stem Cell Directors End Public Session Tonight
April 28, 2010 at 10:08 PM
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| | Directors of the California stem cell agency just concluded their public session tonight without approving any grant applications or taking other significant action. Their session will resume tomorrow morning at the City of Hope in the Los Angeles area. We will have coverage again then. | | |
| $5.9 Million Grant to Duke Scientist Moving Forward Again
April 28, 2010 at 9:18 PM
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| Directors of the California stem cell agency began a discussion tonight of a $5.9 million grant to help lure a Duke University scientist to California despite a statement earlier today that the matter would not be brought up.
James Harrison, outside counsel to CIRM, this afternoon said in an email that the matter would not be considered. Asked about the change this evening, Harrison replied in | | |
| CIRM Directors with Conflicts of Interests on Biology Grants
April 28, 2010 at 8:19 PM
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| Here is the list of the CIRM board members scheduled to be recused from voting on or discussing grant applications this evening on which they have conflicts of interest. You can find the review summaries of the grants here. The list was prepared by CIRM legal staff.
CIRM Basic Biology Award II
Application # Members in Conflict
RB2-01494 Feit,Hawgood,Lansing,Sheehy
RB2-01496 Lansing,Levin,Steward | | |
| Live Coverage of Today's CIRM Directors Meeting
April 28, 2010 at 5:28 PM
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| | We will have live coverage and stories as warranted from today and tomorrow's meeting of the CIRM board of directors. We will be listening via the Internet from our post here on the water in El Salvador. The agenda includes $30 million in grants, perhaps reasons for the delay on the Wechsler-Reya grant, changes in outside contracting policies and a vote to stifle legislation that would reform | | |
| Action Stalled on $5.9 Million CIRM Grant to Recruit Duke Scientist
April 28, 2010 at 3:54 PM
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| The California stem cell agency today called an abrupt halt to scheduled approval of a $5.9 million grant to lure a Duke University cancer stem cell researcher to the Sanford-Burnham Institute in La Jolla, Ca.
No reason was immediately offered for the removal of the grant application from the agenda today of the CIRM directors. James Harrison, outside counsel for CIRM, said in an email,
"This | | |
| Wechsler-Reya Still Mulling Move to California's Burnham
April 28, 2010 at 1:02 PM
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| Cancer stem cell researcher Robert Wechsler-Reya says he has not yet made a decision to leave Duke University and come to California, where he would be the recipient of CIRM's first Research Leadership Award.
Directors of the California stem cell agency today or tomorrow are scheduled to approve a $5.9 million grant for Wechsler-Reya to help lure him and his wife, stem cell scientist Tannishtha | | |
| Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment.
April 28, 2010 at 8:01 AM
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| | Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J Exp Med. 2010 Apr 26; Authors: Morita Y, Ema H, Nakauchi H Hematopoietic stem cells (HSCs) have been extensively characterized based on functional definitions determined by experimental transplantation into lethally irradiated mice. In mice, HSCs are heterogeneous with regard to self-renewal potential, in vitro colony-forming activity, and in vivo behavior. We attempted prospective isolation of HSC subsets with distinct properties among CD34(-/low) c-Kit(+)Sca-1(+)Lin(-) (CD34(-)KSL) cells. CD34(-)KSL cells were divided, based on CD150 expression, into three fractions: CD150(high), CD150(med), and CD150(neg) cells. Compared with the other two fractions, CD150(high) cells were significantly enriched in HSCs, with great self-renewal potential. In vitro colony assays revealed that decreased expression of CD150 was associated with reduced erythroblast/megakaryocyte differentiation potential. All three fractions were regenerated only from CD150(high) cells in recipient mice. Using single-cell transplantation studies, we found ! that a fraction of CD150(high) cells displayed latent and barely detectable myeloid engraftment in primary-recipient mice but progressive and multilineage reconstitution in secondary-recipient mice. These findings highlight the complexity and hierarchy of reconstitution capability, even among HSCs in the most primitive compartment. PMID: 20421392 [PubMed - as supplied by publisher] | | |
| Comparison of ganglioside expression between human adipose- and dental pulp-derived stem cell differentiation into osteoblasts.
April 28, 2010 at 6:56 AM
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| | Comparison of ganglioside expression between human adipose- and dental pulp-derived stem cell differentiation into osteoblasts. Arch Pharm Res. 2010 Apr;33(4):585-91 Authors: Lee SH, Ryu JS, Lee JW, Kwak DH, Ko K, Choo YK Human adipose-derived stem cells (hADSCs) and dental pulp-derived stem cells (hDPSCs) have been considered alternative sources of adult stem cells because of their potential to trans-differentiate into multiple cell lineages. This study investigated the possible role of gangliosides in the osteoblast differentiation of hADSCs and hDPSCs. First, we investigated characterization of hADSCs and hDPSCs using FACS analysis. Mesenchymal stem cell specific markers, CD44 and CD105, were expressed but not hematopoetic markers, CD45 and CD117 in both of hADSCs and hDPSCs. High-performance thin-layer chromatography analysis showed that increased gangliosides were associated with differentiation of hADSCs and hDPSCs into osteoblasts. RT-PCR analysis confirmed that osteoblast specific genes, ALP, BMP-2, collagen were expressed in differentiated osteoblasts, however, the another osteoblast specific gene, osteocalcin, was not expressed. When hADSCs and hDPSCs were cultured under ! osteoblast-differentiation conditions, alkaline phosphatase (ALP) activity was increased in comparison to hADSCs and hDPSCs. Furthermore, specifically both ALP activity and ganglioside expression increased more in hDPSCs-derived osteoblasts than hADSCs-derived osteoblasts. These results suggest that gangliosides play a more important role in regulating the osteoblast-differentiation of hDPSCs compared to hADSCs. PMID: 20422368 [PubMed - in process] | | |
| Stanniocalcin-1 regulates extracellular ATP-induced calcium waves in human epithelial cancer cells by stimulating ATP release from bystander cells.
April 28, 2010 at 6:17 AM
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| | Stanniocalcin-1 regulates extracellular ATP-induced calcium waves in human epithelial cancer cells by stimulating ATP release from bystander cells. PLoS One. 2010;5(4):e10237 Authors: Block GJ, DiMattia GD, Prockop DJ BACKGROUND: The epithelial cell response to stress involves the transmission of signals between contiguous cells that can be visualized as a calcium wave. In some cell types, this wave is dependent on the release of extracellular trinucleotides from injured cells. In particular, extracellular ATP has been reported to be critical for the epithelial cell response to stress and has recently been shown to be upregulated in tumors in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Here, we identify stanniocalcin-1 (STC1), a secreted pleiotrophic protein, as a critical mediator of calcium wave propagation in monolayers of pulmonary (A549) and prostate (PC3) epithelial cells. Addition of STC1 enhanced and blocking STC1 decreased the distance traveled by an extracellular ATP-dependent calcium wave. The same effects were observed when calcium was stimulated by the addition of exogenous ATP. We uncover a positive feedback loop in which STC1 promotes the release of ATP from cells in v! itro and in vivo. CONCLUSIONS/SIGNIFICANCE: The results indicated that STC1 plays an important role in the early response to mechanical injury by epithelial cells by modulating signaling of extracellular ATP. This is the first report to describe STC1 as a modulator or purinergic receptor signaling. PMID: 20422040 [PubMed - in process] | | |
| Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment.
April 28, 2010 at 6:17 AM
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| | Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J Exp Med. 2010 Apr 26; Authors: Morita Y, Ema H, Nakauchi H Hematopoietic stem cells (HSCs) have been extensively characterized based on functional definitions determined by experimental transplantation into lethally irradiated mice. In mice, HSCs are heterogeneous with regard to self-renewal potential, in vitro colony-forming activity, and in vivo behavior. We attempted prospective isolation of HSC subsets with distinct properties among CD34(-/low) c-Kit(+)Sca-1(+)Lin(-) (CD34(-)KSL) cells. CD34(-)KSL cells were divided, based on CD150 expression, into three fractions: CD150(high), CD150(med), and CD150(neg) cells. Compared with the other two fractions, CD150(high) cells were significantly enriched in HSCs, with great self-renewal potential. In vitro colony assays revealed that decreased expression of CD150 was associated with reduced erythroblast/megakaryocyte differentiation potential. All three fractions were regenerated only from CD150(high) cells in recipient mice. Using single-cell transplantation studies, we found ! that a fraction of CD150(high) cells displayed latent and barely detectable myeloid engraftment in primary-recipient mice but progressive and multilineage reconstitution in secondary-recipient mice. These findings highlight the complexity and hierarchy of reconstitution capability, even among HSCs in the most primitive compartment. PMID: 20421392 [PubMed - as supplied by publisher] | | |
| A Novel Technology for Hematopoietic Stem Cell Expansion using Combination of Nanofiber and Growth Factors.
April 28, 2010 at 6:17 AM
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| | A Novel Technology for Hematopoietic Stem Cell Expansion using Combination of Nanofiber and Growth Factors. Recent Pat Nanotechnol. 2010 Apr 26; Authors: Lu J, Aggarwal R, Pompili VJ, Das H Hematopoietic stem cell transplantation has been applied as a standard procedure of treatment for hematological disorders like multiple myeloma and leukemia for several decades. Various sources of stem cells like bone marrow, peripheral blood and umbilical cord blood are used for the transplantation. Among these umbilical cord blood is currently preferred due to the primitiveness of the derived stem cells and minimal possibilities of graft versus host disease or development of graft induced tumors. One of the problems for these sources is the procurement of insufficient number of donor stem cells. Inadequate number of cells may lead to delayed recovery and decrease survivability of the patient. Thus to overcome the limitation of stem cell number, development of an ex-vivo expansion technology is critically important. The recent emerging technology using nanofiber in combination with growth factors has made a significant improvement to the field of regenerative med! icine and a couple of patents have been filed. In this review, we will focus on factors regulating hematopoietic stem cell self-renewal and expansion emphasizing on nanofiber as a supporting matrix. PMID: 20420564 [PubMed - as supplied by publisher] | | |
| Tissue Engineering Strategies for the Regeneration of Orthopedic Interfaces.
April 28, 2010 at 6:13 AM
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| | Tissue Engineering Strategies for the Regeneration of Orthopedic Interfaces. Ann Biomed Eng. 2010 Apr 27; Authors: Lu HH, Subramony SD, Boushell MK, Zhang X A major focus in the field of orthopedic tissue engineering is the development of tissue engineered bone and soft tissue grafts with biomimetic functionality to allow for their translation to the clinical setting. One of the most significant challenges of this endeavor is promoting the biological fixation of these grafts with each other as well as the implant site. Such fixation requires strategic biomimicry to be incorporated into the scaffold design in order to re-establish the critical structure-function relationship of the native soft tissue-to-bone interface. The integration of distinct tissue types (e.g. bone and soft tissues such as cartilage, ligaments, or tendons), necessitates a multi-phased or stratified scaffold with distinct yet continuous tissue regions accompanied by a gradient of mechanical properties. This review discusses tissue engineering strategies for regenerating common tissue-to-tissue interfaces (ligament-to-bone, tendon-to-bone, or cartil! age-to-bone), and the strategic biomimicry implemented in stratified scaffold design for multi-tissue regeneration. Potential challenges and future directions in this emerging field will also be presented. It is anticipated that interface tissue engineering will enable integrative soft tissue repair, and will be instrumental for the development of complex musculoskeletal tissue systems with biomimetic complexity and functionality. PMID: 20422291 [PubMed - as supplied by publisher] | | |
| Rheological properties of peptide-based hydrogels for biomedical and other applications.
April 28, 2010 at 6:13 AM
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| | Rheological properties of peptide-based hydrogels for biomedical and other applications. Chem Soc Rev. 2010 Apr 26; Authors: Yan C, Pochan DJ Peptide-based hydrogels are an important class of biomaterials finding use in food industry and potential use in tissue engineering, drug delivery and microfluidics. A primary experimental method to explore the physical properties of these hydrogels is rheology. A fundamental understanding of peptide hydrogel mechanical properties and underlying molecular mechanisms is crucial for determining whether these biomaterials are potentially suitable for biotechnological uses. In this critical review, we cover the literature containing rheological characterization of the physical properties of peptide and polypeptide-based hydrogels including hydrogel bulk mechanical properties, gelation mechanisms, and the behavior of hydrogels during and after flow (219 references). PMID: 20422104 [PubMed - as supplied by publisher] | | |
| Understanding the effect of mean pore size on cell activity in collagen-glycosaminoglycan scaffolds.
April 28, 2010 at 6:13 AM
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| | Understanding the effect of mean pore size on cell activity in collagen-glycosaminoglycan scaffolds. Cell Adh Migr. 2010 Jul 9;4(3) Authors: Murphy CM, O'Brien FJ Mean pore size is an essential aspect of scaffolds for tissue-engineering. if pores are too small cells cannot migrate in towards the centre of the construct limiting the diffusion of nutrients and removal of waste products. Conversely, if pores are too large there is a decrease in specific surface area available limiting cell attachment. However the relationship between scaffold pore size and cell activity is poorly understood and as a result there are conflicting reports within the literature on the optimal pore size required for successful tissue-engineering. Previous studies in bone tissue-engineering have indicated a range of mean pore sizes (96 mum-150 mum) to facilitate optimal attachment. Other studies have shown a need for large pores (300 mum-800 mum) for successful bone growth in scaffolds. These conflicting results indicate that a balance must be established between obtaining optimal cell attachment and facilitating bone growth. In this commentary we d! iscuss our recent investigations into the effect of mean pore size in collagenglycosaminoglycan (CG) scaffolds with pore sizes ranging from 85 mum-325 mum and how it has provided an insight into the divergence within the literature. PMID: 20421733 [PubMed - as supplied by publisher] | | |
| Cartilage tissue engineering with demineralized bone matrix gelatin and fibrin glue hybrid scaffold: an in vitro study.
April 28, 2010 at 6:13 AM
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| | Cartilage tissue engineering with demineralized bone matrix gelatin and fibrin glue hybrid scaffold: an in vitro study. Artif Organs. 2010 Feb;34(2):161-6 Authors: Wang ZH, He XJ, Yang ZQ, Tu JB To develop a cartilage-like tissue with hybrid scaffolds of demineralized bone matrix gelatin (BMG) and fibrin, rabbit chondrocytes were cultured on hybrid fibrin/BMG scaffolds in vitro. BMG scaffolds were carefully soaked in a chondrocyte-fibrin suspension, which was polymerized by submerging the constructs into thrombin-calcium chloride solution. Engineered cartilage-like tissue grown on the scaffolds was characterized by histology, immunolocalization, scanning electron microscopy, biochemical assays, and analysis of gene expression at different time points of the in vitro culture. The presence of proteoglycan in the fibrin/BMG hybrid constructs was confirmed by positive toluidine blue and alcian blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrices. Chondrogenic properties were further demonstrated by the expression of gene-encoded cartilage-specific markers, collagen type II, and aggrecan core protein. The glycosaminog! lycan production and hydroxyproline content of tissue grown on the fibrin/BMG hybrid scaffolds were higher than that of the BMG group. In conclusion, the fibrin/BMG hybrid scaffolds may serve as a potential cell delivery vehicle and a structural basis for cartilage tissue engineering. PMID: 20420593 [PubMed - in process] | | |
| Laser direct writing of micro- and nano-scale medical devices.
April 28, 2010 at 6:13 AM
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| | Laser direct writing of micro- and nano-scale medical devices. Expert Rev Med Devices. 2010 May;7(3):343-56 Authors: Gittard SD, Narayan RJ Laser-based direct writing of materials has undergone significant development in recent years. The ability to modify a variety of materials at small length scales and using short production times provides laser direct writing with unique capabilities for fabrication of medical devices. In many laser-based rapid prototyping methods, microscale and submicroscale structuring of materials is controlled by computer-generated models. Various laser-based direct write methods, including selective laser sintering/melting, laser machining, matrix-assisted pulsed-laser evaporation direct write, stereolithography and two-photon polymerization, are described. Their use in fabrication of microstructured and nanostructured medical devices is discussed. Laser direct writing may be used for processing a wide variety of advanced medical devices, including patient-specific prostheses, drug delivery devices, biosensors, stents and tissue-engineering scaffolds. PMID: 20420557 [PubMed - in process] | | |
| TruFit CB bone plug: chondral repair, scaffold design, surgical technique and early experiences.
April 28, 2010 at 6:13 AM
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| | TruFit CB bone plug: chondral repair, scaffold design, surgical technique and early experiences. Expert Rev Med Devices. 2010 May;7(3):333-41 Authors: Melton JT, Wilson AJ, Chapman-Sheath P, Cossey AJ The TruFit CB osteochondral scaffold plug is a commercially available and licensed scaffold implant for the treatment of chondral and osteochondral defects of the knee. A number of surgical techniques have been described that are designed to achieve neocartilaginous tissue cover of a chondral defect, but many result in fibrocartilage tissue, not type II collagen hyaline cartilage. This fibrocartilage layer can fail with high shear forces in the knee joint, and lead to ongoing articular surface irregularity and subsequent secondary arthritic change. Recent research and clinical interest has focused on employing tissue-engineering techniques utilizing scaffolds in an attempt to obtain cartilage repair tissue that is histologically and biomechanically superior. The TruFit CB implant is one such device. This article describes the techniques of attempted chondral repair and the problems that can be experienced. Current concepts in chondral scaffold design are discussed! , and the surgical technique and early experiences with the TruFit CB implant are presented. PMID: 20420556 [PubMed - in process] | | |
| Use of stem cells in the biological repair of articular cartilage.
April 28, 2010 at 6:13 AM
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| | Use of stem cells in the biological repair of articular cartilage. Expert Opin Biol Ther. 2010 Jan;10(1):43-55 Authors: Nelson L, Fairclough J, Archer C Importance of the field: Articular cartilage is avascular, aneural, and renowned for its poor capacity to repair after damage. For decades scientists and clinicians have deliberated over the potential to repair or regenerate articular cartilage and to date many techniques have been used in an attempt to create the best possible repair tissue. Areas covered in this review: This review article summarises surgical interventions that have been developed since the late 1940's; covering conservative strategies, invasive techniques and touching upon latest advancements involving stem cells and tissue engineering. What will the reader gain: The reader will gain a sound understanding into the history and background of strategies that have developed in attempts to reverse clinical symptoms of damaged or diseased articular cartilage. The article provides an insight into the plethora of potential repair mechanisms, and reviews future developments involving stem cells and biom! aterials. Take home message: Although work is still in its infancy, the use of stem cells in the biological repair of articular cartilage provides a promising outlook onto future developments; advancing from strategies and techniques that are already in use. PMID: 20420516 [PubMed - as supplied by publisher] | | |
| Regulatory considerations in application of encapsulated cell therapies.
April 28, 2010 at 6:13 AM
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| | Regulatory considerations in application of encapsulated cell therapies. Adv Exp Med Biol. 2010;670:31-7 Authors: van Zanten J, de Vos P The encapsulation of tissue in semi-permeable membranes is a technology with high potential and in due time several new therapies based on this technology will be tested in clinical trials. Recent, new legislation requires that these investigational medicinal products used in clinical trials Phase I must be produced according to Good Manufacturing Practice (GMP). Consequently, the activities of GMP are expanding to the field of research and researchers might need to change developed protocols in order to meet GMP legislation. This chapters gives an overview of the overall guidelines covering GMP and more specific guidelines dealing with cell based therapies and gene therapy. PMID: 20384216 [PubMed - indexed for MEDLINE] | | |
| Facile synthesis of functional polyperoxides by radical alternating copolymerization of 1,3-dienes with oxygen.
April 28, 2010 at 6:13 AM
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| | Facile synthesis of functional polyperoxides by radical alternating copolymerization of 1,3-dienes with oxygen. Chem Rec. 2009;9(5):247-57 Authors: Sato E, Matsumoto A We have developed a facile synthesis of degradable polyperoxides by the radical alternating copolymerization of 1,3-diene monomers with molecular oxygen at an atmospheric pressure. In this review, the synthesis, the degradation behavior, and the applications of functional polyperoxides are summarized. The alkyl sorbates as the conjugated 1,3-dienes gave a regiospecific alternating copolymer by exclusive 5,4-addition during polymerization and the resulting polyperoxides decomposed by the homolysis of a peroxy linkage followed by successive beta-scissions. The preference of 5,4-addition was well rationalized by theoretical calculations. The degradation of the polyperoxides occurred with various stimuli, such as heating, UV irradiation, a redox reaction with amines, and an enzyme reaction. The various functional polyperoxides were synthesized by following two methods, one is the direct copolymerization of functional 1,3-dienes, and the other is the functionalization ! of the precursor polyperoxides. Water soluble polyperoxides were also prepared, and the LCST behavior and the application to a drug carrier in the drug delivery system were investigated. In order to design various types of degradable polymers and gels we developed a method for the introduction of dienyl groups into the precursor polymers. The resulting dienyl-functionalized polymers were used for the degradable gels. The degradable branched copolymers showed a microphase-separated structure, which changed owing to the degradation of the polyperoxide segments. PMID: 19927311 [PubMed - indexed for MEDLINE] | | |
| CIRM Millions Help Snag Duke star Wechsler-Reya for Burnham
April 28, 2010 at 12:03 AM
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| The recipient of CIRM's first Research Leadership Award, with $5.9 million in funding, is Robert Wechsler-Reya (at left) of Duke University, a reliable source said today.
He is leaving Duke and joining the Sanford Burnham Institute in La Jolla, Ca., where the CIRM-funded research is expected to be performed. Sanford Burnham is providing "an extremely generous commitment of laboratory space, | | | | 
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