|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | SAN FRANCISCO – Only four members of the public attended the first day of a blue-ribbon review of the operations of the $3 billion California stem cell agency during the brief period permitted for public comment.
The panel shut down its public session after about one hour and moved from the Marriott Hotel in San Francisco to CIRM headquarters to continue the meetings behind closed doors.
The | | | | | | | | | | | | | | | | | | | | | | | | The California stem cell agency confirmed this morning that the public remains barred from the key sessions of this week's sweeping review of the operations of the $3 billion public enterprise.
In response to a query, Don Gibbons, chief communications officer for CIRM, said,
"The public is only invited to the sessions that are marked as public."We raised the question because CIRM removed | | | | | | | | | | | | | | | | | | | | | | | | | Synthetic elastin hydrogels that are coblended with heparin display substantial swelling, increased porosity, and improved cell penetration. J Biomed Mater Res A. 2010 Oct 11; Authors: Tu Y, Mithieux SM, Annabi N, Boughton EA, Weiss AS Synthetic elastin hydrogels are useful tissue engineering scaffolds because they present cell binding sequences and display physical performance similar to that of human elastic tissue. Small pores and a low porosity can limit cellular penetration into elastin scaffolds. To overcome this problem, glycosaminoglycans were coblended with tropoelastin during the formation of synthetic elastin hydrogels. Heparin and dermatan sulfate increased the pore size and porosity of the hydrogels. Heparin was particularly effective as it enlarged the pore size from 6.6 ± 2.1 μm to 23.8 ± 8.5 μm, and generated structures occasionally separated by finely fenestrated thin walls, which allowed human dermal fibroblast cells to migrate as deep as ∼300 μm into the hydrogel under diffusion-limiting static culture conditions. Most cells displayed spindle-like morphology, appeared histologically normal and presented intact nuclei, as expected for a viable population. Hydrogel swelling studies showed that each of the hydrogels contracted as the temperature was raised from 4°C to 37°C; synthetic elastin-heparin was least affected by temperature with a contraction of only 22.4 ± 1.2%, which would facilitate its transition from cold storage to body temperature. All hydrogels displayed similar compression moduli of 5.5 ± 0.4 to 6.9 ± 0.6 kPa. Compressive elastic energy losses for synthetic elastin-heparin and synthetic elastin were 33.7 ± 1.3% and 31.7 ± 2.2% respectively. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20939056 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Growth and differentiation of bone marrow stromal cells on biodegradable polymer scaffolds: An in vitro study. J Biomed Mater Res A. 2010 Oct 11; Authors: Xue Y, Dånmark S, Xing Z, Arvidson K, Albertsson AC, Hellem S, Finne-Wistrand A, Mustafa K A fundamental component of bone tissue engineering is an appropriate scaffold as a carrier for osteogenic cells. The aim of the study was to evaluate the response of human bone marrow stromal cells (BMSC) to scaffolds made of three biodegradable polymers: poly(L-lactide-co-ε-caprolactone) (poly(LLA-co-CL)), poly(L-lactide-co-1,5dioxepan-2-one) (poly(LLA-co-DXO)), and poly(L-lactide) (poly(LLA)). Cellular response was evaluated in terms of attachment, proliferation, and differentiation. SEM disclosed earlier cell attachment and better spreading on poly(LLA-co-CL) and poly(LLA-co-DXO) scaffolds than on poly(LLA) after 1 h. At 24 h and 14 days postseeding, BMSCs had spread well, forming multiple cellular layers on the scaffolds. Cell proliferation was higher on poly(LLA-co-CL) and on poly(LLA-co-DXO) than on poly(LLA) after 1 and 7 days. Cell growth cycles of BMSC were longer on the scaffolds than on coverslips. After 7 and 14 days cultivation on scaffolds, the expression of osteogenic markers such as ALP, Col I, OPN, and Runx2 were stimulated by BMSC, which indicating that poly(LLA-co-DXO), poly(LLA-co-CL), and poly(LLA) could support the osteogenic differentiation of BMSC in vitro. Poly(LLA-co-CL) and poly(LLA-co-DXO) promoted better attachment and growth of BMSC than poly(LLA). BMSC also retained their osteogenic differentiation potential, indicating biological activity of BMSC on the scaffolds. The promising results of this in vitro study indicate that these copolymers warrant further evaluation for potential application in bone tissue engineering. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 20939051 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The potential of pulsed low intensity ultrasound to stimulate chondrocytes matrix synthesis in agarose and monolayer cultures. Med Biol Eng Comput. 2010 Oct 12; Authors: Vaughan NM, Grainger J, Bader DL, Knight MM Pulsed low intensity ultrasound (PLIUS) has been used successfully for bone fracture repair and has therefore been suggested for cartilage regeneration. However, previous in vitro studies with chondrocytes show conflicting results as to the effect of PLIUS on the elaboration of extracellular matrix. This study tests the hypothesis that PLIUS, applied for 20 min/day, stimulates the synthesis of sulphated glycosaminoglycan (sGAG) by adult bovine articular chondrocytes cultured in either monolayer or agarose constructs. For both culture models, PLIUS at either 30 or 100 mW/cm(2) intensity had no net effect on the total sGAG content. Although PLIUS at 100 mW/cm(2) did induce a 20% increase in sGAG content at day 2 of culture in agarose, this response was lost by day 5. Intensities of 200 and 300 mW/cm(2) resulted in cell death probably due to heating from the ultrasound transducers. The lack of a sustained up-regulation of sGAG synthesis may reflect the suggestion that PLIUS only induces a stimulatory effect in the presence of a tissue injury response. These results suggest that PLIUS has a limited potential to provide an effective method of stimulating matrix production as part of a tissue engineering strategy for cartilage repair. PMID: 20938751 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mode of action studies of the novel bisquaternary bisnaphthalimide MT02 against Staphylococcus aureus. Antimicrob Agents Chemother. 2010 Oct 11; Authors: Menzel TM, Tischer M, François P, Nickel J, Schrenzel J, Bruhn H, Albrecht A, Lehmann L, Holzgrabe U, Ohlsen K Screening of various bisquaternary bisnaphthalimides against a variety of human pathogens revealed one compound, designated MT02, with strong inhibitory effects against Gram-positive bacteria. The minimal inhibitory concentrations ranged from 0.31 μg/ml against community-acquired methicillin-resistant Staphylococcus aureus (MRSA) lineage USA300 to 20 μg/ml against Streptococcus pneumonia. Radioactive whole cell labeling experiments indicated a strong impact of MT02 on bacterial DNA-replication. DNA-microarray studies generated a transcriptional signature characterized by stronger expression of genes involved in DNA-metabolism, DNA-replication, SOS-response and transport of positively charged compounds. Furthermore, surface plasmon resonance and gel retardation experiments demonstrated direct binding of MT02 to DNA in a concentration dependent, reversible and sequence-unspecific manner. The data presented suggest that the bisquaternary bisnaphthalimide MT02 exerts anti-gram-positive activity by binding to DNA and thereby prohibiting appropriate DNA-replication. PMID: 20937782 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A functionalizable reverse thermal gel based on a polyurethane/PEG block copolymer. Biomaterials. 2010 Oct 9; Authors: Park D, Wu W, Wang Y Injectable reverse thermal gels have great potentials as biomaterials for tissue engineering and drug delivery. However, most existing gels lack functional groups that can be modified with biomolecules that can guide cell/material interactions. We created an amine-functionalized ABA block copolymer, poly(ethylene glycol)-poly(serinol hexamethylene urethane), or ESHU. This reverse thermal gel consists of a hydrophobic block (B): poly(serinol hexamethylene urethane) and a hydrophilic block (A): poly(ethylene glycol). The polymer was characterized by GPC, FTIR and (1)H FTNMR. Rheological study demonstrated that ESHU solution in phosphate-buffered saline initiated phase transition at 32 °C and reached maximum elastic modulus at 37 °C. The in vitro degradation tests performed in PBS and cholesterol esterase solutions revealed that the polymer was hydrolyzable and the presence of cholesterol esterase greatly accelerated the hydrolysis. The in vitro cytotoxicity tests carried out using baboon smooth muscle cells demonstrated that ESHU had good cytocompatibility with cell viability indistinguishable from tissue culture treated polystyrene. Subcutaneous implantation in rats revealed well tolerated accurate inflammatory response with moderate ED-1 positive macrophages in the early stages, which largely resolved 4 weeks post-implantation. We functionalized ESHU with a hexapeptide, Ile-Lys-Val-Ala-Val-Ser (IKVAVS), which gelled rapidly at body temperature. We expect this new platform of functionalizable reverse thermal gels to provide versatile biomaterials in tissue engineering and regenerative medicine. PMID: 20937526 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Mathematical modeling of degradation for biodegradable bulk-erosive polymers: size-dependence in tissue engineering scaffold and drug delivery system. Acta Biomater. 2010 Oct 8; Authors: Chen Y, Zhou S, Li Q Degradation of polymeric biomaterials, which are widely exploited in tissue engineering and drug delivery systems, has drawn significant attention in recent years. This paper aims to develop a mathematical model that combines stochastic hydrolysis and mass transport to simulate the polymeric degradation and erosion process. The hydrolysis reaction is modeled in a discrete fashion by a fundamental stochastic process and an additional autocatalysis effect induced by local carboxylic acid concentration in terms of the continuous diffusion equation. The illustrative examples of micro-particles and tissue scaffolds demonstrate the applicability of the presented mathematical model. It is found that the diffusive transport plays a critical role in determining the degradation pathway, whilst the autocatalysis makes the degradation size-dependent. The modeling results show a good agreement with the experimental data in literature, in which the hydrolysis rate, polymer architecture and matrix size actually work together to determine the characteristics of degradation and erosion process of bulk-erosive polymer devices. The proposed degradation model exhibits a great potential for the design optimization of drug carriers and tissue scaffolds. PMID: 20937415 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Microbial Exo-Polysaccharides for Biomedical Applications. Mini Rev Med Chem. 2010 Nov 12; Authors: Shih IL The productions and applications of various microbial exopolysaccharides have been under intensive researches over the past few decades. Some of these exopolysaccharides are commercial available and some are currently under intensive development; they include ionic heteropolysaccharide and neutral homopolysaccharide. These extracellular polymers constitute a structurally diverse class of biological macromolecules with a wide range of physiochemical properties which are the basis for the different applications in the broad fields of pharmacy and medicine. They have found applications in such diverse biomedical fields as ophthalmology, orthopedic surgery, tissue engineering, implantation of medical devices and artificial organs, prostheses, dentistry, bone repair and drug delivery. PMID: 20937027 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Engineering blood vessels using stem cells: innovative approaches to treat vascular disorders. Expert Rev Cardiovasc Ther. 2010 Oct;8(10):1433-45 Authors: Kusuma S, Gerecht S Vascular disease is the leading cause of mortality in the USA, providing the impetus for new treatments and technologies. Current therapies rely on the implantation of stents or grafts to treat injured blood vessels. However, these therapies may be immunogenic or may incompletely recover the functional integrity of the vasculature. In light of these shortcomings, cell-based therapies provide new treatment options to heal damaged areas with more suitable substitutes. Current clinical trials employing stem cell-based therapies involve the transfusion of harvested endothelial progenitor cells. While the results from these trials have been encouraging, utilizing tissue-engineered approaches could yield technologically advanced solutions. This article discusses engineered stem cell-based therapies from three angles: the differentiation of adult stem cells, such as mesenchymal stem cells and endothelial progenitor cells, into vascular lineages; investigation of human embryonic stem cells and induced pluripotent stem cells as inexhaustible sources of vascular cells; and tissue-engineering approaches, which incorporate these vascular progenitor cells into biomimetic scaffolds to guide regeneration. The optimal solution to vascular disease lies at the interface of these technologies – embedding differentiated cells into engineered scaffolds to impart precise control over vascular regeneration. PMID: 20936930 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Porous poly(vinyl alcohol)-alginate gel hybrid construct for neocartilage formation using human nasoseptal cells. J Surg Res. 2010 Oct;163(2):331-6 Authors: Bichara DA, Zhao X, Hwang NS, Bodugoz-Senturk H, Yaremchuk MJ, Randolph MA, Muratoglu OK BACKGROUND: Limited options exist for the restoration of craniofacial cartilage. Autologous tissue or porous polyethylene is currently used for nasal and auricular reconstruction. Both options are associated with drawbacks, including donor site morbidity and implant extrusion. Poly(vinyl alcohol) (PVA) is a non-degradable flexible biocompatible polymer than can be engineered to mimic the properties of cartilage. The goal of this study was to engineer a biosynthetic hybrid construct using a combination of PVA-alginate hydrogels and human nasal septum chondrocytes. MATERIALS AND METHODS: Chondrocytes isolated from human nasal septum cartilage were expanded and mixed with 2% sodium alginate hydrogel. The chondrocyte-alginate mix was injected into a non-degradable porous PVA hydrogel, creating biosynthetic constructs. A group of these constructs were implanted into the subcutaneous environment of nude mice, while the other group was cultured in a spinner flask bioreactor system for 10 d and then implanted. After 6 wk in vivo, the histologic, biochemical, and biomechanical properties were examined. RESULTS: Histological analysis demonstrated sulfated glycosaminoglycans and deposition of collagen type II in constructs from both groups. Constructs cultured in the bioreactor system prior in vivo implantation demonstrated higher levels of DNA, glycosaminoglycans, and hydroxyproline. An increase of 22% in the compressive strength of the engineered constructs exposed to the bioreactor was also observed. CONCLUSION: A novel porous PVA-alginate gel hybrid was used to successfully engineer human cartilage in vivo. A 10-d period of bioreactor culturing increased levels of DNA, glycosaminoglycans, hydroxyproline, and the compressive modulus of the constructs. PMID: 20538292 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The effect of cell density on the maturation and contractile ability of muscle derived cells in a 3D tissue-engineered skeletal muscle model and determination of the cellular and mechanical stimuli required for the synthesis of a postural phenotype. J Cell Physiol. 2010 Nov;225(3):646-53 Authors: Mudera V, Smith AS, Brady MA, Lewis MP The successful engineering of a truly biomimetic model of skeletal muscle could have a significant impact on a number of biomedical disciplines. Although a variety of techniques are currently being developed, there is, as of yet, no widely available and easily reproducible culture system for the synthesis of 3D artificial muscle tissues. In attempting to generate such a model it is essential to optimise any protocol in order to generate a tissue that best represents the in vivo environment. Since the maturation of muscle derived cells in culture is critically dependent on density, a major factor to be addressed in the development of these models is the ideal concentration at which to seed cells in order to generate an optimal response. In studying the effect of cell density on the performance of cells in an established 3D collagen based model of skeletal muscle, we demonstrate that an optimum density does exist in terms of peak force generation and myogenic gene expression data. Greater densities however, lead to the formation of a more physiologically relevant tissue with a phenotype characteristic of slow, postural muscle. PMID: 20533296 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Using poly(lactide-co-glycolide) electrospun scaffolds to deliver cultured epithelial cells to the cornea. Regen Med. 2010 May;5(3):395-401 Authors: Deshpande P, McKean R, Blackwood KA, Senior RA, Ogunbanjo A, Ryan AJ, MacNeil S AIMS: To assess the potential of electrospun poly(lactide-co-glycolide) membranes to provide a biodegradable cell carrier system for limbal epithelial cells. MATERIAL & METHODS: 50:50 poly(lactide-co-glycolide) scaffolds were spun, sterilized and seeded with primary rabbit limbal epithelial cells. Cells were cultured on the scaffolds for 2 weeks and then examined by confocal microscopy, cryosectioning and scanning-electron microscopy. The tensile strength of scaffolds before and after annealing and sterilization was also studied. RESULTS: The limbal cells had formed a continuous multilayer of cells on either side of the scaffold. Scaffolds with cells showed signs of the onset of degradation within 2 weeks in culture media at 37 degrees C. Scaffolds that were annealed resulted in a more brittle and stiff mat. CONCLUSIONS: We suggest this carrier membrane could be used as a replacement for the human amniotic membrane in the treatment of limbal stem cell deficiency, lowering the risk of disease transmission to the patient. PMID: 20455650 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Interview: Affordability at the cutting edge: stem cell therapy for ocular surface reconstruction. Regen Med. 2010 May;5(3):337-40 Authors: Vemuganti GK, Sangwan VS PMID: 20455646 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Institutional profile: Harvard Stem Cell Institute. Regen Med. 2010 May;5(3):331-5 Authors: Reeve BC PMID: 20455645 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine cell therapies: numbers of units manufactured and patients treated between 1988 and 2010. Regen Med. 2010 May;5(3):307-13 Authors: Mason C, Manzotti E PMID: 20455641 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Basement membrane components are key players in specialized extracellular matrices. Cell Mol Life Sci. 2010 Sep;67(17):2879-95 Authors: Kruegel J, Miosge N More than three decades ago, basement membranes (BMs) were described as membrane-like structures capable of isolating a cell from and connecting a cell to its environment. Since this time, it has been revealed that BMs are specialized extracellular matrices (sECMs) with unique components that support important functions including differentiation, proliferation, migration, and chemotaxis of cells during development. The composition of these sECM is as unique as the tissues to which they are localized, opening the possibility that such matrices can fulfill distinct functions. Changes in BM composition play significant roles in facilitating the development of various diseases. Furthermore, tissues have to provide sECM for their stem cells during development and for their adult life. Here, we briefly review the latest research on these unique sECM and their components with a special emphasis on embryonic and adult stem cells and their niches. PMID: 20428923 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Lipid profile components and risk of ischemic stroke: a role for the pleiotropic effects of statins. Arch Neurol. 2010 Oct;67(10):1284-5 Authors: Connick P, Stacpoole SR PMID: 20937963 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | A functionalizable reverse thermal gel based on a polyurethane/PEG block copolymer. Biomaterials. 2010 Oct 9; Authors: Park D, Wu W, Wang Y Injectable reverse thermal gels have great potentials as biomaterials for tissue engineering and drug delivery. However, most existing gels lack functional groups that can be modified with biomolecules that can guide cell/material interactions. We created an amine-functionalized ABA block copolymer, poly(ethylene glycol)-poly(serinol hexamethylene urethane), or ESHU. This reverse thermal gel consists of a hydrophobic block (B): poly(serinol hexamethylene urethane) and a hydrophilic block (A): poly(ethylene glycol). The polymer was characterized by GPC, FTIR and (1)H FTNMR. Rheological study demonstrated that ESHU solution in phosphate-buffered saline initiated phase transition at 32 °C and reached maximum elastic modulus at 37 °C. The in vitro degradation tests performed in PBS and cholesterol esterase solutions revealed that the polymer was hydrolyzable and the presence of cholesterol esterase greatly accelerated the hydrolysis. The in vitro cytotoxicity tests carried out using baboon smooth muscle cells demonstrated that ESHU had good cytocompatibility with cell viability indistinguishable from tissue culture treated polystyrene. Subcutaneous implantation in rats revealed well tolerated accurate inflammatory response with moderate ED-1 positive macrophages in the early stages, which largely resolved 4 weeks post-implantation. We functionalized ESHU with a hexapeptide, Ile-Lys-Val-Ala-Val-Ser (IKVAVS), which gelled rapidly at body temperature. We expect this new platform of functionalizable reverse thermal gels to provide versatile biomaterials in tissue engineering and regenerative medicine. PMID: 20937526 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Potentialities of Induced Pluripotent Stem (iPS) Cells for Treatment of Diseases. Curr Mol Med. 2010 Nov 12; Authors: Chakraborty C, Shah KD, Cao WG, Hsu CH, Wen ZH, Lin CS Induced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, and effectiveness of iPS cells. Then we have emphasized the potential applications of iPS cells in pharmaceutical and medical sectors, such as, study of cellular mechanisms for spectrum of disease entities, disease-specific iPS cell lines for drugs discovery and development, toxicological studies of drugs development, personalized medicine, and regenerative medicine. PMID: 20937020 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Stem cells--belief, hope and knowledge] Ugeskr Laeger. 2010 Sep 20;172(38):2593 Authors: Hansen MB PMID: 20920400 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Mouse Emi2 as a distinctive regulatory hub in second meiotic metaphase. Development. 2010 Oct;137(19):3281-91 Authors: Suzuki T, Suzuki E, Yoshida N, Kubo A, Li H, Okuda E, Amanai M, Perry AC The oocytes of vertebrates are typically arrested at metaphase II (mII) by the cytostatic factor Emi2 until fertilization. Regulatory mechanisms in Xenopus Emi2 (xEmi2) are understood in detail but contrastingly little is known about the corresponding mechanisms in mammals. Here, we analyze Emi2 and its regulatory neighbours at the molecular level in intact mouse oocytes. Emi2, but not xEmi2, exhibited nuclear targeting. Unlike xEmi2, separable N- and C-terminal domains of mouse Emi2 modulated metaphase establishment and maintenance, respectively, through indirect and direct mechanisms. The C-terminal activity was mapped to the potential phosphorylation target Tx(5)SxS, a destruction box (D-box), a lattice of Zn(2+)-coordinating residues and an RL domain. The minimal region of Emi2 required for its cytostatic activity was mapped to a region containing these motifs, from residue 491 to the C terminus. The cytostatic factor Mos-MAPK promoted Emi2-dependent metaphase establishment, but Mos autonomously disappeared from meiotically competent mII oocytes. The N-terminal Plx1-interacting phosphodegron of xEmi2 was apparently shifted to within a minimal fragment (residues 51-300) of mouse Emi2 that also contained a calmodulin kinase II (CaMKII) phosphorylation motif and which was efficiently degraded during mII exit. Two equimolar CaMKII gamma isoform variants were present in mII oocytes, neither of which phosphorylated Emi2 in vitro, consistent with the involvement of additional factors. No evidence was found that calcineurin is required for mouse mII exit. These data support a model in which mammalian meiotic establishment, maintenance and exit converge upon a modular Emi2 hub via evolutionarily conserved and divergent mechanisms. PMID: 20724447 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | Making a last minute change, the California stem cell agency has decided to allow more time for public comment during the sweeping review this week of its operations, but still will apparently bar the public from hearing testimony by witnesses.
The first public comment session will come tomorrow morning at 8 a.m. Other public comment sessions will be on Thursday and Friday mornings.
In the | | | | | | | | | |  | |  | |  |
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