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| $22 Million for Biology: CIRM Directors OK Two Reviewer-rejected Grants
April 29, 2010 at 6:27 PM
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| California stem cell directors today approved more than $22 million in basic biology grants, overturning negative decisions by reviewers on two applications.
The directors ratified all 14 grants supported by reviewers, plus applications from researchers at UC Davis and the Sanford-Burnham Institute in La Jolla. The total was well under the $30 million that CIRM budgeted for the biology grant | | |
| Duke Researcher Wins $6 million Grant From California -- With a Condition
April 29, 2010 at 4:50 PM
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| California will give a Duke University cancer stem cell research nearly $6 million if he comes to work in the Golden State at the Sanford-Burnham Institute in La Jolla.
Directors of California's $3 billion stem cell agency, as expected, today approved the research grant for Robert Wechsler-Reya. The grant is the first installment in a $44 million program aimed at luring eight stellar | | |
| CIRM Directors Meeting Underway
April 29, 2010 at 1:05 PM
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| | Directors of the California stem cell agency have begun their meeting today. They are currently discussing applications for basic biology grants. Reviewers recommended funding 14 for a total of $19.6 million. Last night directors discussed scores on grants that were not recommended for funding, raising the possibility that some might be funded. | | |
| CIRM Receives Another $112 Million
April 29, 2010 at 1:02 PM
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| Alan Trounson, president of the California stem cell agency, last night outlined his priorities, provided more details on a key strategic review of its program and sketched out upcoming CIRM events.
Directors were also told that the agency received an additional $112 million as the result of recent California state bond sales. That should ensure CIRM has enough cash to operate until the end of | | |
| Current status of stem cell therapy in heart failure.
April 29, 2010 at 8:12 AM
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| | Current status of stem cell therapy in heart failure. Curr Cardiol Rep. 2010 May;12(3):199-208 Authors: Codina M, Elser J, Margulies KB Inspired by studies demonstrating the potential for new myocyte formation within adult mammalian hearts, an ongoing explosion of research is elucidating the biology of cardiac myogenesis and angiogenesis. Multiple lines of research suggest that disease-associated activation of endogenous cardiac repair processes are often insufficient to overcome the cell death resulting from myocardial infarction and chronic heart failure. In this context, this review highlights current evidence supporting endogenous cardiac repair mechanisms in human hearts, recent progress with clinical application of myocardial cell therapy, and complementary efforts to manipulate endogenous myocardial repair processes using a variety of tissue engineering strategies. The goal of this overview is to demonstrate that the insights and opportunities derived from each of these lines of inquiry are mutually complementary for ultimately achieving the goal of therapeutic cardiac regeneration. PMID: 20424962 [PubMed - in process] | | |
| Transplantation of retinoic acid treated murine embryonic stem cells & behavioural deficit in Parkinsonian rats.
April 29, 2010 at 8:12 AM
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| | Transplantation of retinoic acid treated murine embryonic stem cells & behavioural deficit in Parkinsonian rats. Indian J Med Res. 2010 Apr;131:536-44 Authors: Fathi F, Altiraihi T, Mowla SJ, Movahedin M BACKGROUND & OBJECTIVES: Stem cell therapy has been considered as an ideal option for the treatment of Parkinson's disease. Murine embryonic stem cells (mESCs)-derived dopaminergic (DA) neurons may substitute the degenerated neurons in the brain. In this study we generated highly enriched cultures of neural progenitors from mESCs and grafted them into the striatum of Parkinsonian rats to evaluate their ability to improve impaired function. METHODS: An animal model was developed for Parkinson's disease in rats, using 6- hydroxy dopamine. The animals were divided into two groups: (i) the control group treated with culture medium only, and (ii) the experimental group, which was treated with a murine ESC cell-line (CCE). Transplanted cells were labelled with bromodeoxyuridine (BrdU), exposed to retinoic acid and then engrafted within the striatum of the rat model. RESULTS: Treated ES cells by retinoic acid were found to relieve apomorphine-induced asymmetr! ic motor behaviour. Immunohistochemistry results revealed tyrosine hydroxlase immunoreactivity in engrafted cells 15 days after transplantation. Further, the ultrastructural examination along with cresyl violet staining confirmed that the cells gained neuronal and glial appearance. INTERPRETATION & CONCLUSIONS: Our data demonstrate that retinoic acid treatment and transplanting ESC cells to the lessioned brain can lead to the generation of putative dopaminergic neurons and functional recovery in parkinsonian rat model with. PMID: 20424305 [PubMed - in process] | | |
| Fiber-modified adenovirus can mediate human adipose tissue-derived mesenchymal stem cell-based anti-angiogenic gene therapy.
April 29, 2010 at 6:51 AM
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| | Fiber-modified adenovirus can mediate human adipose tissue-derived mesenchymal stem cell-based anti-angiogenic gene therapy. Biotechnol Lett. 2010 Apr 28; Authors: Liu H, Chu Y, Lou G A fiber-modified adenovirus (rAd5F11B), loaded with the Kringle1-5 gene (rAd-K1-5) was used to infect human adipose tissue-derived mesenchymal stem cells (HAMSCs). At a multiplicity of infection of 20, the transfection efficiency in HAMSCs was 90% and the cell expansion and differentiation of infected HAMSCs were not significantly suppressed. HAMSCs infected with rAd-K1-5 expressed the exogenous Kringle1-5 protein, an angiogenic inhibitor, and conditioned media from HAMSCs expressing the Kringle1-5 protein blocked VEGF-induced neovascularization both in vitro and in vivo. rAd5F11B may therefore be a promising gene transfer vector in HAMSCs-based anti-angiogenic gene therapy because of its low toxicity and high transfection efficiency. PMID: 20424891 [PubMed - as supplied by publisher] | | |
| In vivo imaging and monitoring of transplanted stem cells: clinical applications.
April 29, 2010 at 6:29 AM
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| | In vivo imaging and monitoring of transplanted stem cells: clinical applications. Curr Cardiol Rep. 2010 Jan;12(1):51-8 Authors: Rodriguez-Porcel M Regenerative medicine using stem cells has appeared as a potential therapeutic alternative for coronary artery disease, and stem cell clinical studies are currently on their way. However, initial results of these studies have provided mixed information, in part because of the inability to correlate organ functional information with the presence/absence of transplanted stem cells. Recent advances in molecular biology and imaging have allowed the successful noninvasive monitoring of transplanted stem cells in the living subject. In this article, different imaging strategies (direct labeling, indirect labeling with reporter genes) to study the viability and biology of stem cells are discussed. In addition, the limitations of each approach and imaging modality (eg, single photon emission computed tomography, positron emission tomography, and MRI) and their requirements for clinical use are addressed. Use of these strategies will be critical as the different regenerati! ve therapies are being tested for clinical use. PMID: 20425184 [PubMed - in process] | | |
| Crosstalk between histone modifications maintains the developmental pattern of gene expression on a tissue-specific locus.
April 29, 2010 at 6:29 AM
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| | Crosstalk between histone modifications maintains the developmental pattern of gene expression on a tissue-specific locus. Epigenetics. 2010 May 16;5(4) Authors: Hosey AM, Chaturvedi CP, Brand M Genome wide studies have provided a wealth of information related to histone modifications. Particular modifications, which can encompass both broad and discrete regions, are associated with certain genomic elements and gene expression status. Here we focus on how studies on the beta-globin gene cluster can complement the genome wide effort through the thorough dissection of histone modifying protein crosstalk. The beta-globin locus serves as a model system to study both regulation of gene expression driven at a distance by enhancers and mechanisms of developmental switching of clustered genes. We investigate recent studies, which uncover that histone methyltransferases, recruited at the beta-globin enhancer, control gene expression by long range propagation on chromatin. Specifically, we focus on how seemingly antagonistic complexes, such as those including MLL2, G9a and UTX, can cooperate to functionally regulate developmentally controlled gene expression. Final! ly, we speculate on the mechanisms of chromatin modifying complex propagation on genomic domains. PMID: 20424518 [PubMed - as supplied by publisher] | | |
| Emerging use of stem cells in regenerative medicine.
April 29, 2010 at 6:29 AM
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| | Emerging use of stem cells in regenerative medicine. Biochem J. 2010;428(1):11-23 Authors: Teo AK, Vallier L Stem cells represent a unique opportunity for regenerative medicine to cure a broad number of diseases for which current treatment only alleviates symptoms or retards further disease progression. However, the number of stem cells available has speedily increased these past 10 years and their diversity presents new challenges to clinicians and basic scientists who intend to use them in clinics or to study their unique properties. In addition, the recent possibility to derive pluripotent stem cells from somatic cells using epigenetic reprogramming has further increased the clinical interest of stem cells since induced pluripotent stem cells could render personalized cell-based therapy possible. The present review will attempt to summarize the advantages and challenges of each type of stem cell for current and future clinical applications using specific examples. PMID: 20423328 [PubMed - in process] | | |
| Human embryonic stem cell-derived cardiomyocytes: demonstration of a portion of cardiac cells with fairly mature electrical phenotype.
April 29, 2010 at 6:29 AM
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| | Human embryonic stem cell-derived cardiomyocytes: demonstration of a portion of cardiac cells with fairly mature electrical phenotype. Exp Biol Med (Maywood). 2010 Apr 1;235(4):522-30 Authors: Pekkanen-Mattila M, Chapman H, Kerkelä E, Suuronen R, Skottman H, Koivisto AP, Aalto-Setälä K Cardiomyocytes (CMs) derived from human embryonic stem cells (hESC) provide a promising tool for the pharmaceutical industry. In this study the electrical properties and maturation of hESC-CM derived using two differentiation methods were compared and the suitability of hESC-CMs as a cell model for the assessment of drug-induced repolarization delay was evaluated. CMs were differentiated either in END-2 co-culture or by spontaneous differentiation. Action potentials (APs) were recorded from cells in spontaneously beating areas using the whole-cell patch-clamp technique. The hESC-CMs exhibited predominantly a ventricular-like phenotype with heterogeneous properties. Heterogeneity was indicative of the spectrum of hESC-CM maturation from embryonic-like with AP upstroke velocities <30 V/s and maximum diastolic potential (MDP) of close to -60 mV to more mature with values >150 V/s and -80 mV, respectively. The mean MDP was -70 mV and a significant difference was! observed between the two differentiation methods (-66 versus -75 mV, P < 0.001). The age of the CMs did not correlate with phenotype maturation. The addition of the hERG blocker E-4031 and the sodium channel modulator veratridine significantly prolonged the AP duration. Furthermore, proarrhythmic indices were induced. In conclusion, the main observation was the heterogeneity in electrical properties of the hESC-CMs and this was observed with both differentiation methods. One-third of the hESC-CMs exhibited fairly mature electrophysiological properties, suggesting that mature CMs could be obtained from hESCs. However, improved differentiation methods are needed to produce homogeneous mature human CMs for pharmaceutical and toxicological applications. PMID: 20407085 [PubMed - indexed for MEDLINE] | | |
| Smooth-Muscle-Like Cells Derived from Human Embryonic Stem Cells Support and Augment Cord-Like Structures In Vitro.
April 29, 2010 at 6:00 AM
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| | Smooth-Muscle-Like Cells Derived from Human Embryonic Stem Cells Support and Augment Cord-Like Structures In Vitro. Stem Cell Rev. 2010 Apr 28; Authors: Vo E, Hanjaya-Putra D, Zha Y, Kusuma S, Gerecht S Engineering vascularized tissue is crucial for its successful implantation, survival, and integration with the host tissue. Vascular smooth muscle cells (v-SMCs) provide physical support to the vasculature and aid in maintaining endothelial viability. In this study, we show an efficient derivation of v-SMCs from human embryonic stem cells (hESCs), and demonstrate their functionality and ability to support the vasculature in vitro. Human ESCs were differentiated in monolayers and supplemented with platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor-beta 1 (TGF-beta1). Human ESC-derived smooth-muscle-like cells (SMLCs) were found to highly express specific smooth muscle cell (SMC) markers-including alpha-smooth muscle actin, calponin, SM22, and smooth muscle myosin heavy chain-to produce and secrete fibronectin and collagen, and to contract in response to carbachol. In vitro tubulogenesis assays revealed that these hESC-derived SMLCs interacte! d with human endothelial progenitor cell (EPCs) to form longer and thicker cord-like structures in vitro. We have demonstrated a simple protocol for the efficient derivation of highly purified SMLCs from hESCs. These in vitro functional SMLCs interacted with EPCs to support and augment capillary-like structures (CLSs), demonstrating the potential of hESCs as a cell source for therapeutic vascular tissue engineering. PMID: 20425149 [PubMed - as supplied by publisher] | | |
| Current status of stem cell therapy in heart failure.
April 29, 2010 at 6:00 AM
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| | Current status of stem cell therapy in heart failure. Curr Cardiol Rep. 2010 May;12(3):199-208 Authors: Codina M, Elser J, Margulies KB Inspired by studies demonstrating the potential for new myocyte formation within adult mammalian hearts, an ongoing explosion of research is elucidating the biology of cardiac myogenesis and angiogenesis. Multiple lines of research suggest that disease-associated activation of endogenous cardiac repair processes are often insufficient to overcome the cell death resulting from myocardial infarction and chronic heart failure. In this context, this review highlights current evidence supporting endogenous cardiac repair mechanisms in human hearts, recent progress with clinical application of myocardial cell therapy, and complementary efforts to manipulate endogenous myocardial repair processes using a variety of tissue engineering strategies. The goal of this overview is to demonstrate that the insights and opportunities derived from each of these lines of inquiry are mutually complementary for ultimately achieving the goal of therapeutic cardiac regeneration. PMID: 20424962 [PubMed - in process] | | |
| Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: An update.
April 29, 2010 at 6:00 AM
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| | Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: An update. Med Sci Monit. 2010 Apr 28;16(5):RA93-100 Authors: Lu JM, Nurko J, Weakley SM, Jiang J, Kougias P, Lin PH, Yao Q, Chen C Creosote bush, Larrea tridentata, is known as chaparral or greasewood in the United States and as gobernadora or hediondilla in Mexico. Nordihydroguaiaretic acid (NDGA), the main metabolite of the creosote bush, has been shown to have promising applications in the treatment of multiple diseases, including cardiovascular diseases, neurological disorders and cancers. Creosote bush is a promising agent of North American herbal medicine, and it has extensive pharmacological effects and specific mechanisms of actions. This review provides an update of recent in vitro and in vivo research about NDGA and describes experimental studies using NDGA as antioxidant. Also, potential medical uses based on the effects of NDGA on the cardiovascular, immune and neurological systems; cancer; tissue engineering; as well as pharmacokinetics and toxicity are discussed.<br /> PMID: 20424564 [PubMed - in process] | | |
| Modulating cell adhesion dynamics on carbon nanotube monolayer engineered with extracellular matrix proteins.
April 29, 2010 at 6:00 AM
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| | Modulating cell adhesion dynamics on carbon nanotube monolayer engineered with extracellular matrix proteins. ACS Appl Mater Interfaces. 2010 Apr;2(4):1038-47 Authors: Cai N, Wong CC, Gong YX, Tan SC, Chan V, Liao K Although it has been demonstrated that carbon nanotubes (CNTs) may have potentials for tissue engineering applications because of their unparalleled physical properties, little has been known on the cell adhesion mechanisms on model CNT monolayer pertaining to the design of novel cell therapeutics device. In this study, the adhesion dynamics of primary porcine esophageal fibroblasts (PEFs) on CNT monolayer were elucidated with confocal reflectance interference contrast microscopy (C-RICM) integrating with phase contrast microscopy. Moreover, CNT monolayer (CNT-ML) was functionalized with two typical extracellular matrix (ECM) proteins including collagen type I (COL) and fibronectin (FN) in order to promote its biocompatibility. First, it is shown by atomic force microscopy that the topographical features of CNT-ML were dependent on the types of immobilized ECM protein. Second, significant time lag in adhesion contact evolution (around 10 min) for PEFs was found on! both CNT-ML and CNT-COL compared to the negligible time lag on CNT-FN. It was found that adhesion energy of PEFs on the CNT-COL and CNT-FN surfaces reached steady state at 60 and 30 min after cell seeding compared to 70 min on CNT-ML surface. At steady state, the adhesion energy of PEFs on the CNT-COL and CNT-FN surfaces was about twice as much than that on the CNT-ML surface. Moreover, immobilization of collagen or fibronectin on CNT monolayer led to an increase in seeding efficiency and proliferation rate of PEFs. Scanning electron microscopy and immunostaining together demonstrated that PEFs displayed an elongated morphology and highly polarized actin network on both CNT-COL and CNT-FN surfaces, whereas PEFs displayed nonuniform cell morphology and actin organization on the CNT-ML surface. Overall, our results demonstrated that the biophysical responses and biological behavior of PEFs on unmodified or functionalized CNT monolayer were different. Functionalization of CNT! through extracellular matrix protein immobilization effective! ly promo tes cell adhesion and proliferation, which may provide information for designing CNT-based biomaterials or novel cell therapeutics devices in biomedical engineering. PMID: 20423124 [PubMed - in process] | | |
| Incorporating protein gradient into electrospun nanofibers as scaffolds for tissue engineering.
April 29, 2010 at 6:00 AM
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| | Incorporating protein gradient into electrospun nanofibers as scaffolds for tissue engineering. ACS Appl Mater Interfaces. 2010 Apr;2(4):1025-30 Authors: Shi J, Wang L, Zhang F, Li H, Lei L, Liu L, Chen Y We report a simple but straightforward approach to produce nanofiber scaffolds with incorporated protein gradient for cell culture studies. Standard electrospinning technique was used to fabricate a high-porosity random fiber matrix. Protein molecules were then deposited in the fiber matrix by a controlled filling method, allowing the generation of a concentration gradient on the sample. When cultured with NIH 3T3 cells, it was found that the cell population on the fiber matrix depends strongly on the protein concentration. The cell morphology observation also showed the effect of the hybrid system containing both a fibrillar network and surface-coated protein gradient, revealing a different behavior of cell spreading in comparison with the experimental data of cell culture without fibers or without protein gradient. PMID: 20423122 [PubMed - in process] | | | | 
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