|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | A key committee of the directors of the California stem cell agency tonight moved to take a fresh look at the selection of a new chairman of the $3 billion organization and to conduct a self-evaluation of the board itself.
The proposal now goes to the full board of directors at their meeting in Burlingame tomorrow.
The Governance committee also agreed with a request made one year ago by the | | | | | | | | | | | | | | | | | | | | | | | | Earlier today, the California Stem Cell Report asked the office of state Controller John Chiang to comment concerning the appointment of Bert Lubin to the CIRM governing board. Here is what Hallye Jordan, Chiang's spokesperson, sent.
"Controller Chiang was thrilled to appoint Dr. Bert Lubin for the position reserved for a California nonprofit academic and research institute because he is | | | | | | | | | | | | | | | | | | | | | | | | | The Salk item on Jan. 26, 2011, incorrectly stated that William Brody was being replaced on the CIRM board by Bert Lubin. Lubin actually replaced John Reed. | | | | | | | | | | | | | | | | | | | | | | | | Bert Lubin, new CIRM board
member
The Salk Institute has lost its seat on the 29-member governing board of the $3 billion California stem cell agency.
The La Jolla, Ca., research enterprise had held a position on the board since its inception in 2004. Most recently, William Brody, president of Salk, which has received $37 million in CIRM grants, filled the slot. Brody was appointed in | | | | | | | | | | | | | | | | | | | | | | | | This is a busy week for the California stem cell agency, but not all the action is in Burlingame where CIRM board convenes tonight for a preliminary round, followed by the main event tomorrow.
Two other state bodies will be looking at CIRM at meetings in Los Angeles and Sacramento. One of the panels is the only entity specifically charged with oversight of the $3 billion agency's finances. That | | | | | | | | | | | | | | | | | | | | | | | | | The California Stem Cell Report will provide live coverage tomorrow of the meeting of the governing board of the $3 billion California stem cell agency. For those who want to listen in as well, you can find instructions for the Internet broadcast of the directors' session on the meeting agenda. The session is scheduled to begin at 9 a.m. PST, but usually starts late. | | | | | | | | | | | | | | | | | | | | | | | | | Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells. Biomaterials. 2011 Jan 22; Authors: Bhang SH, Cho SW, La WG, Lee TJ, Yang HS, Sun AY, Baek SH, Rhie JW, Kim BS Stem cells offer significant therapeutic promise for the treatment of ischemic disease. However, stem cells transplanted into ischemic tissue exhibit limited therapeutic efficacy due to poor engraftment in vivo. Several strategies for improving the survival and engraftment of stem cells in ischemic tissue have been developed including transplantation in combination with growth factor delivery, genetic modification of stem cells, and the use of cell-transplantation scaffolds. Here, we demonstrate that human adipose-derived stromal cells (hADSCs) cultured and grafted as spheroids exhibit improved therapeutic efficacy for ischemia treatment. hADSCs were cultured in monolayer or spheroids. Spheroid cultures were more effective in preconditioning hADSCs to a hypoxic environment, upregulating hypoxia-adaptive signals (i.e., stromal cell-derived factor-1α and hypoxia-inducible factor-1α), inhibiting apoptosis, and enhancing secretion of both angiogenic and anti-apoptotic factors (i.e., hepatocyte growth factor, vascular endothelial growth factor, and fibroblast growth factor 2) compared to monolayer cultures. Moreover, cell harvesting following spheroid cultures avoided damage to extracellular matrices due to harsh proteolytic enzyme treatment, thereby preventing anoikis (apoptosis induced by a lack of cell-matrix interaction). Following intramuscular transplantation to ischemic hindlimbs of athymic mice, hADSC spheroids showed improved cell survival, angiogenic factor secretion, neovascularization, and limb survival as compared to hADSCs grafted as dissociated cells. Taken together, spheroid cultures precondition hADSCs to a hypoxic environment, and grafting hADSCs as spheroids to ischemic limbs improves therapeutic efficacy for ischemia treatment due to enhanced cell survival and paracrine effects. Spheroid-based cell delivery could be a simple and effective strategy for improving stem cell therapy for ischemic diseases, eliminating the need for growth factor delivery, biomaterial scaffolds or genetic modification. PMID: 21262528 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Embryonic stem cells induce ectopic bone formation in rats. Biomed Mater Eng. 2010 Jan 1;20(6):371-380 Authors: Kahle M, Wiesmann HP, Berr K, Depprich RA, Kübler NR, Naujoks C, Cohnen M, Ommerborn MA, Meyer U, Handschel J Background: Surgery often leads to massive destruction of the skeleton. Cell-based bone reconstruction therapies promise new therapeutic opportunities for the repair of bone. Embryonic stem cells (ESCs) can be differentiated into osteogenic cells and are a potential cell source for bone tissue engineering. The purpose of this in vivo study was to investigate the bone formation in various constructs containing ESCs (with and without micromass technology) and insoluble collagenous bone matrix (ICBM).Methods: Murine ESCs were cultured as monolayer cultures as well as micromasses and seeded on ICBM. These constructs were implanted in immunodeficient rats. After one week, one, two and three months CT-scans were performed to detect any calcifications and the rats were sacrificed.Results: The radiological examination shows a steep increase of the mineralized tissue in group 1 (ICBM+seeded ESC). This increase can be considered as statistical significant. In contrast, the volume of the mineralization in group 2 (ICBM+ESC-spheres) and group 3 (ESC-spheres) does not increase significantly during the study.Conclusion: ESCs in combination with ICBM do promote ectopic bone formation in vivo. Thus, this cell population as well as the biomaterial ICBM might be promising components for bone tissue engineering. PMID: 21263183 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Condensed cellular seeded collagen gel as an improved biomaterial for tissue engineering of articular cartilage. Biomed Mater Eng. 2010 Jan 1;20(6):317-328 Authors: Mueller-Rath R, Gavénis K, Andereya S, Mumme T, Albrand M, Stoffel M, Weichert D, Schneider U Three-dimensional autologous chondrocyte implantation based on collagen gel as matrix scaffold has become a clinically applied treatment for focal defects of articular cartilage. However, the low biomechanical properties of collagen gel makes intraoperative handling difficult and creates the risk of early damages to the vulnerable implant. The aim of the study was to create a stabilized form of collagen gel and to evaluate its biomechanical and biochemical properties.Collagen type-I gel was seeded with human articular chondrocytes. 20 samples were subject to condensation which was achieved mechanically by compression and filtration. Control samples were left uncondensed. From both types of gels 10 samples were used for initial biomechanical evaluation by means of unconfined compression and 10 samples were cultivated under standard conditions in vitro. Following cultivation the samples were evaluated by conventional histology and immunohistochemistry. The proliferation rate was calculated and matrix gene expression was quantified by real-time PCR.The biomechanical tests revealed a higher force carrying capacity of the condensed specimens. Strain rate dependency and relaxation was seen in both types of collagen gel representing viscoelastic material properties. Cells embedded within the condensed collagen gel were able to produce extracellular matrix proteins and showed proliferation.Condensed collagen gel represents a mechanically improved type of biomaterial which is suitable for three-dimensional autologous chondrocyte implantation. PMID: 21263178 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Chemical control of FGF-2 release for promoting calvarial healing with adipose stem cells. J Biol Chem. 2011 Jan 24; Authors: Kwan MD, Sellmyer MA, Quarto N, Ho AM, Wandless TJ, Longaker MT Chemical control of protein secretion using a small molecule approach provides a powerful tool to optimize tissue engineering strategies by regulating the spatial and temporal dimensions which are exposed to a specific protein. We placed fibroblast growth factor 2 (FGF-2) under conditional control of a small molecule and demonstrated greater than fifty-fold regulation of FGF-2 release as well as tunability, reversibility, and functionality in vitro. We then applied conditional control of FGF-2 secretion to a cellular-based, skeletal tissue engineering construct, consisting of adipose stem cells (ASCs) on a biomimetic scaffold to promote bone formation in a murine critical-sized calvarial defect model. ASCs are an easily harvested and abundant source of postnatal multipotent cells and have previously been demonstrated to regenerate bone in critical-sized defects. These results suggest that chemically controlled FGF-2 secretion can significantly increase bone formation by ASCs in vivo. This study represents a novel approach towards refining protein delivery for tissue engineering applications. PMID: 21262969 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Nucleation and growth of mineralized bone matrix on silk-hydroxyapatite composite scaffolds. Biomaterials. 2011 Jan 22; Authors: Bhumiratana S, Grayson WL, Castaneda A, Rockwood DN, Gil ES, Kaplan DL, Vunjak-Novakovic G We describe a composite hydroxyapatite (HA)-silk fibroin scaffold designed to induce and support the formation of mineralized bone matrix by human mesenchymal stem cells (hMSCs) in the absence of osteogenic growth factors. Porous three-dimensional silk scaffolds were extensively used in our previous work for bone tissue engineering and showed excellent biodegradability and biocompatibility. However, silk is not an osteogenic material and has a compressive stiffness significantly lower than that of native bone. In the present study, we explored the incorporation of silk sponge matrices with HA (bone mineral) micro-particles to generate highly osteogenic composite scaffolds capable of inducing the in vitro formation of tissue-engineered bone. Different amounts of HA were embedded in silk sponges at volume fractions of 0%, 1.6%, 3.1% and 4.6% to enhance the osteoconductive activity and mechanical properties of the scaffolds. The cultivation of hMSCs in the silk/HA composite scaffolds under perfusion conditions resulted in the formation of bone-like structures and an increase in the equilibrium Young's modulus (up to 4-fold or 8-fold over 5 or 10 weeks of cultivation, respectively) in a manner that correlated with the initial HA content. The enhancement in mechanical properties was associated with the development of the structural connectivity of engineered bone matrix. Collectively, the data suggest two mechanisms by which the incorporated HA enhanced the formation of tissue engineered bone: through osteoconductivity of the material leading to increased bone matrix production, and by providing nucleation sites for new mineral resulting in the connectivity of trabecular-like architecture. PMID: 21262535 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Integrative design of a poly(ethylene glycol)-poly(propylene glycol)-alginate hydrogel to control three dimensional biomineralization. Biomaterials. 2011 Jan 22; Authors: Cha C, Kim ES, Kim IW, Kong H A mineralized polymeric matrix has been extensively studied to understand biomineralization processes and to further regulate phenotypic functions of various cells involved in osteogenesis and physiological homeostasis. It has been often proposed that several matrix variables including charge density, hydrophobicity, and pore size play vital roles in modulating composition and morphology of minerals formed within a three dimensional (3D) matrix. However, the aspects have not yet been systematically examined because a tool enabling the independent control of the matrix variables is lacking. This study presents an advanced integrative strategy to control morphology and composition of biominerals with matrix properties, by using a hydrogel formulated to independently control charge density, hydrophobicity, and porosity. The hydrogel consists of poly(ethylene glycol) monomethacrylate (PEGmM), poly(propylene glycol) monomethacrylate (PPGmM), and methacrylic alginate (MA), so the charge density and hydrophobicity of the hydrogel can be separately controlled with mass fractions of MA and PPGmM. Also, hydrogels which present only nano-sized pores, termed nanoporous hydrogels, are lyophilized and rehydrated to prepare the hydrogels containing micro-sized pores, termed microporous hydrogels. We find that increasing the mass fractions of MA and PPGmM of the microporous hydrogel promotes the growth of apatite layers because of the increases in the charge density, hydrophobicity and pore size. In contrast, increasing mass fractions of MA and PPGmM of the nanoporous hydrogel enhances the formation of calcium carbonate minerals. The dependency of the mineralization on hydrogel variables is related to the change in supersaturation of mineral ions. Overall, the results of this study will be highly useful to better understand the interplay of matrix variables in biomineralization and to design a wide array of mineralized matrix potentially used in cell therapies and tissue engineering. PMID: 21262532 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The effects of fixed electrical charge on chondrocyte behavior. Acta Biomater. 2011 Jan 21; Authors: Dadsetan M, Pumberger M, Casper ME, Shogren K, Giuliani M, Ruesink T, Hefferan TE, Currier BL, Yaszemski MJ In this study, we have compared the effects of negative and positive fixed charge on chondrocyte behavior in vitro. Electrical charges have been incorporated into oligo(poly(ethylene glycol) fumarate) (OPF) using small charged monomers such as sodium methacrylate (SMA) and (2-(methacryloyloxy) ethyl)-trimethyl ammonium chloride (MAETAC) to produce negatively and positively charged hydrogels, respectively. The hydrogel physical and electrical properties were characterized through measuring and calculating the swelling ratio and zeta potential, respectively. Our results revealed that the properties of these OPF modified hydrogels varied according to the concentration of charged monomers. Zeta potential measurements demonstrated that the electrical property of the OPF hydrogel surfaces changed due to incorporation of SMA and MAETAC and that this change in electrical property was dose-dependent. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy was used to determine the hydrogel surface composition. To assess the effects of surface properties on chondrocyte behavior, primary chondrocytes isolated from rabbit ears were seeded as a monolayer on top of the hydrogels. We demonstrated that the cells remained viable over 7 days and began to proliferate while seeded on top of the hydrogels. Collagen type II staining was positive in all samples; however, the intensity of the stain was higher on negatively charged hydrogels. Similarly, GAG production was significantly higher on negatively charged hydrogels compared to neutral hydrogel. Reverse transcription polymerase chain reaction showed up-regulation of collagen type II and down-regulation of collagen type I on the negatively charged hydrogels. These findings indicate that charge plays an important role in establishing an appropriate environment for chondrocytes and hence in the engineering of cartilage. Thus, further investigation into charged hydrogels for cartilage tissue engineering is merited. PMID: 21262395 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Ectopic osteogenesis of immortalized human bone marrow mesenchymal stem cells and heterogeneous bone]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010 Dec;24(12):1515-9 Authors: Teng Y, Hu Y, Li X, Wang Z, Bai J, Guan Y To provide the seed cells for bone tissue engineering, to establish immortalized human bone marrow mesenchymal stem cells (MSCxj) and to investigate the ectopic osteogenesis of MSCxj. PMID: 21261105 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Ethical care and use of cadavers: A call for a policy. Anat Sci Educ. 2011 Jan;4(1):53-54 Authors: Bernanke DH PMID: 21265039 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Silk Fibroin Conduits: A Cellular and Functional Assessment of Peripheral Nerve Repair. Ann Plast Surg. 2011 Jan 21; Authors: Ghaznavi AM, Kokai LE, Lovett ML, Kaplan DL, Marra KG Silk fibroin conduits were designed with appropriate porosity for peripheral nerve repair. The aim of this work was to use these conduits to examine cell inflammatory responses and functional recovery in a sciatic nerve defect model. A total of 45 randomized Lewis rats were used to create an 8-mm defect bridged by a silk guide, commercial collagen guide, or an autograft. After 1, 4, and 8 weeks, macrophage recruitment, percentage of newly formed collagen, number of myelinated axons, and gastrocnemius muscle mass were evaluated. Following 8 weeks, ED1+ cells in autograft and silk conduits decreased to <1% and 17% of week 1 values, respectively. Collagen formation revealed no difference all measured time points, suggesting a similar foreign body response. Myelinated axon counts within the silk guide revealed a greater number of proximal spouts and distal connections than collagen guides. Gastrocnemius weights demonstrated a 27% decrease between silk and autografts after 8 weeks. This study demonstrates that, in addition to tailorable degradation rates, our silk conduits possess a favorable immunogenicity and remyelination capacity for nerve repair. PMID: 21263296 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Molecular structure, mechanical behavior and failure mechanism of the C-terminal cross-link domain in type I collagen. J Mech Behav Biomed Mater. 2011 Feb;4(2):153-161 Authors: Uzel SG, Buehler MJ Collagen is a key constituent in structural materials found in biology, including bone, tendon, skin and blood vessels. Here we report a first molecular level model of an entire overlap region of a C-terminal cross-linked type I collagen assembly and carry out a nanomechanical characterization based on large-scale molecular dynamics simulation in explicit water solvent. Our results show that the deformation mechanism and strength of the structure are greatly affected by the presence of the cross-link, and by the specific loading condition of how the stretching is applied. We find that the presence of a cross-link results in greater strength during deformation as complete intermolecular slip is prevented, and thereby particularly affects larger deformation levels. Conversely, the lack of a cross-link results in the onset of intermolecular sliding during deformation and as a result an overall weaker structure is obtained. Through a detailed analysis of the distribution of deformation by calculating the molecular strain we show that the location of largest strains does not occur around the covalent bonding region, but is found in regions further away from this location. The insight developed from understanding collagenous materials from a fundamental molecular level upwards could play a role in advancing our understanding of physiological and disease states of connective tissues, and also enable the development of new scaffolding material for applications in regenerative medicine and biologically inspired materials. PMID: 21262493 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Cytoplast containing reprogramming-related factors from human embryonic stem cells arrested at metaphase. Dev Growth Differ. 2011 Jan;53(1):18-25 Authors: Du L, Lin G, Lu G Generating pluripotent stem cells directly from a patient's somatic cells is one of the major methods to avoid rejection in future regenerative medicine. It is reported that human embryonic stem cells (hESCs) are able to reprogram the nuclei of fully differentiated human somatic cells, apparently conferring on them a pluripotent state. However, the ability of the cytoplasts from enucleated hESCs to reprogram somatic cells causes much controversy. Here we detect the location of pluripotency-related factors such as Oct4/Nanog/Sox2 in the hESCs at division and non-division stage and obtain the cytoplasts of hESCs by centrifugation. We demonstrate for the first time that the cytoplast from hESCs arrested at the division phase of cell the cycle contains the reprogramming factors and this kind of cytoplast can be obtained through gradient centrifugation. These give us direct proof of the possibility of reprogramming somatic cell using cytoplast of hESCs and make this a possible method for getting patient-specific pluripotent cells without extrinsic DNA introduction. PMID: 21261607 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells. Biomaterials. 2011 Jan 22; Authors: Bhang SH, Cho SW, La WG, Lee TJ, Yang HS, Sun AY, Baek SH, Rhie JW, Kim BS Stem cells offer significant therapeutic promise for the treatment of ischemic disease. However, stem cells transplanted into ischemic tissue exhibit limited therapeutic efficacy due to poor engraftment in vivo. Several strategies for improving the survival and engraftment of stem cells in ischemic tissue have been developed including transplantation in combination with growth factor delivery, genetic modification of stem cells, and the use of cell-transplantation scaffolds. Here, we demonstrate that human adipose-derived stromal cells (hADSCs) cultured and grafted as spheroids exhibit improved therapeutic efficacy for ischemia treatment. hADSCs were cultured in monolayer or spheroids. Spheroid cultures were more effective in preconditioning hADSCs to a hypoxic environment, upregulating hypoxia-adaptive signals (i.e., stromal cell-derived factor-1α and hypoxia-inducible factor-1α), inhibiting apoptosis, and enhancing secretion of both angiogenic and anti-apoptotic factors (i.e., hepatocyte growth factor, vascular endothelial growth factor, and fibroblast growth factor 2) compared to monolayer cultures. Moreover, cell harvesting following spheroid cultures avoided damage to extracellular matrices due to harsh proteolytic enzyme treatment, thereby preventing anoikis (apoptosis induced by a lack of cell-matrix interaction). Following intramuscular transplantation to ischemic hindlimbs of athymic mice, hADSC spheroids showed improved cell survival, angiogenic factor secretion, neovascularization, and limb survival as compared to hADSCs grafted as dissociated cells. Taken together, spheroid cultures precondition hADSCs to a hypoxic environment, and grafting hADSCs as spheroids to ischemic limbs improves therapeutic efficacy for ischemia treatment due to enhanced cell survival and paracrine effects. Spheroid-based cell delivery could be a simple and effective strategy for improving stem cell therapy for ischemic diseases, eliminating the need for growth factor delivery, biomaterial scaffolds or genetic modification. PMID: 21262528 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Resveratrol in cardiovascular health and disease. Ann N Y Acad Sci. 2011 Jan;1215(1):22-33 Authors: Petrovski G, Gurusamy N, Das DK Resveratrol, initially used for cancer therapy, has shown beneficial effects against most degenerative and cardiovascular diseases from atherosclerosis, hypertension, ischemia/reperfusion, and heart failure to diabetes, obesity, and aging. The cardioprotective effects of resveratrol are associated with its preconditioning-like action potentiated by its adaptive response. During preconditioning, small doses of resveratrol can exert an adaptive stress response, forcing the expression of cardioprotective genes and proteins such as heat shock and antioxidant proteins. Similarly, resveratrol can induce autophagy, another form of stress adaptation for degrading damaged or long-lived proteins, as a first line of protection against oxidative stress. Resveratrol's interaction with multiple molecular targets of diverse intracellular pathways (e.g., action on sirtuins and FoxOs through multiple transcription factors and protein targets) intertwines with those of the autophagic pathway to give support in the modified redox environment after stem cell therapy, which leads to prolonged survival of cells. The successful application of resveratrol in therapy is based upon its hormetic action similar to any toxin: exerting beneficial effects at lower doses and cytotoxic effects at higher doses. PMID: 21261638 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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