| |  | | | | | | | | | | | | | | | |  | | | | | | | | | | | | | | | | | | | | | | | | Directors of the California stem cell agency appear ready to commission a $1 million "gold standard" study of its operations with the hope that it will pave the way for voter approval of billions more for stem cell research, perhaps as early as November 2012.
The proposal is scheduled to be voted on at the CIRM board meeting next Wednesday and Thursday meeting at Stanford. However, few details | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Author and Harvard business professor Rosabeth Moss Kanter weighed in this week on "big traps in small lapses."
The case in point was the recent resignation of HP CEO Mark Hurd, a man who made more than $66,000 a day, because he fudged a $20,000 expense report.
Kanter asked,
"How can very smart, accomplished people do such stupid things?"Kanter, whose 18 books have won her recognition as one | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Shlomo Melmed
The governing board for the $3 billion California stem cell agency has a new member – Shlomo Melmed, who is senior vice president for academic affairs and dean of the medical faculty at Cedars-Sinai Medical Center in Los Angeles.
Gov. Arnold Schwarzenegger named Melmed to replace Ricardo Azziz, who left California to head the Medical College of Georgia. Azziz was also a top | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Can HIV be cured with stem cell therapy? Nat Biotechnol. 2010 Aug;28(8):807-10 Authors: Deeks SG, McCune JM PMID: 20697404 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | de novo MYOCARDIAL REGENERATION: ADVANCES AND PITFALLS. Antioxid Redox Signal. 2010 Aug 9; Authors: Haider KH, Buccini S, Ahmed RP, Ashraf M The capability of adult tissue derived stem cells for cardiogenesis has been extensively studied in experimental animals and clinical studies for treatment of post-ischemic cardiomyopathy. The less than anticipated improvement in the heart function in most clinical studies with skeletal myoblasts and bone marrow cells has warranted a search for alternative sources of stem cells. Despite their multilineage differentiation potential, ethical issues, teratogenicity and tissue rejection are main obstacles in developing clinically feasible methods for embryonic stem (ES) cell transplantation into patients. A decade long research on ES cells has paved the way for discovery of alternative approaches for generating pluripotent stem cells. Genetic manipulation of somatic cells for pluripotency genes reprograms the cells to pluripotent status. Efforts are currently focused to make reprogramming protocols safer for clinical applications of the reprogrammed cells. We summarizes the advancements and complicating features of stem cell therapy and discuss the decade and a half long efforts made by stem cell researchers for moving the field from bench to the bedside as an adjunct therapy or as an alternative to the contemporary therapeutic modalities for routine clinical application. The review also provides a special focus on the advancements made in the field of somatic cell reprogramming. PMID: 20695792 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Adjuvant engineering for cancer immunotherapy: Development of a synthetic TLR2 ligand with increased cell adhesion. Cancer Sci. 2010 Apr 5; Authors: Akazawa T, Inoue N, Shime H, Kodama K, Matsumoto M, Seya T The development of effective immunoadjuvants for tumor immunotherapy is of fundamental importance. The use of Mycobacterium bovis bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) in tumor immunotherapy has been examined in various clinical applications. Because BCG-CWS is a macromolecule that cannot be chemically synthesized, the development of an alternative synthetic molecule is necessary to ensure a constant supply of adjuvant. In the present study, a new adjuvant was designed based on the structure of macrophage-activating lipopeptide (MALP)-2, which is a Toll-like receptor (TLR)-2 ligand similar to BCG-CWS. Macrophage-activating lipopeptide-2, [S-(2,3-bispalmitoyloxypropyl)Cys (P2C) - GNNDESNISFKEK], originally identified in a Mycoplasma species, is a lipopeptide that can be chemically synthesized. A MALP-2 peptide was substituted with a functional motif, RGDS, creating a novel molecule named P2C-RGDS. RGDS was selected because its sequence constitutes an integrin-binding motif and various integrins are expressed in immune cells including dendritic cells (DCs). Thus, this motif adds functionality to the ligand. P2C-RGDS activated DCs and splenocytes more efficiently than MALP-2 over short incubation times in vitro, and the RGDS motif contributed to their activation. Furthermore, P2C-RGDS showed higher activity than MALP-2 in inducing migration of DCs to draining lymph node, and in inhibiting tumor growth in vivo. This process of designing and developing synthetic adjuvants has been named "adjuvant engineering," and the evaluation and improvement of P2C-RGDS constitutes a first step in the development of stronger synthetic adjuvants in the future. (Cancer Sci 2010). PMID: 20507323 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Characterization of the complete fiber network topology of planar fibrous tissues and scaffolds. Biomaterials. 2010 Jul;31(20):5345-54 Authors: D'Amore A, Stella JA, Wagner WR, Sacks MS Understanding how engineered tissue scaffold architecture affects cell morphology, metabolism, phenotypic expression, as well as predicting material mechanical behavior has recently received increased attention. In the present study, an image-based analysis approach that provides an automated tool to characterize engineered tissue fiber network topology is presented. Micro-architectural features that fully defined fiber network topology were detected and quantified, which include fiber orientation, connectivity, intersection spatial density, and diameter. Algorithm performance was tested using scanning electron microscopy (SEM) images of electrospun poly(ester urethane)urea (ES-PEUU) scaffolds. SEM images of rabbit mesenchymal stem cell (MSC) seeded collagen gel scaffolds and decellularized rat carotid arteries were also analyzed to further evaluate the ability of the algorithm to capture fiber network morphology regardless of scaffold type and the evaluated size scale. The image analysis procedure was validated qualitatively and quantitatively, comparing fiber network topology manually detected by human operators (n = 5) with that automatically detected by the algorithm. Correlation values between manual detected and algorithm detected results for the fiber angle distribution and for the fiber connectivity distribution were 0.86 and 0.93 respectively. Algorithm detected fiber intersections and fiber diameter values were comparable (within the mean +/- standard deviation) with those detected by human operators. This automated approach identifies and quantifies fiber network morphology as demonstrated for three relevant scaffold types and provides a means to: (1) guarantee objectivity, (2) significantly reduce analysis time, and (3) potentiate broader analysis of scaffold architecture effects on cell behavior and tissue development both in vitro and in vivo. PMID: 20398930 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | The role of simvastatin in the osteogenesis of injectable tissue-engineered bone based on human adipose-derived stromal cells and platelet-rich plasma. Biomaterials. 2010 Jul;31(20):5325-35 Authors: Zhou Y, Ni Y, Liu Y, Zeng B, Xu Y, Ge W An injectable tissue-engineered bone (ITB) composed of human adipose-derived stromal cells (hADSCs) and platelet-rich plasma (hPRP) was preliminarily constructed, but its osteogenic capability needs improving. This study aimed to evaluate if simvastatin can be applied as a bone anabolic agent for this ITB. We found 0.01 microm, 0.1 microm, and 1 microm simvastatin could induce hADSCs' osteoblastic differentiation in vitro that accompanied with non-inhibition on cell proliferation, high alkaline phosphatase activity, more mineralization deposition and more expression of osteoblast-related genes such as osteocalcin, core binding factor alpha1, bone morphogenetic protein-2, vascular endothelial growth factor, and basic fibroblast growth factor. Simvastatin at 1 mum seemed the most optimal concentration due to its high osteocalcin secretion in media (P < 0.01). Quantitative mineralization assay also showed 1 microm SIM had the most obvious synergistic effect on hPRP's induction for matrix mineralization of hADSCs (P < 0.01). When 1 microm Simvastatin was applied to this ITB to restore the critical-sized calvarial defects in mice, more bone formation was observed in defected regions, and the peripheries just outside the defect margins by X-ray analysis, and H&E staining. These findings indicate that simvastatin at optimal concentrations can be used to promote this ITB's osteogenesis. However, simvastatin's effects on this ITB await long-term investigation. PMID: 20381859 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Apical polarity in three-dimensional culture systems: where to now? J Biol. 2010;9(1):2 Authors: Inman JL, Bissell MJ Delineation of the mechanisms that establish and maintain the polarity of epithelial tissues is essential to understanding morphogenesis, tissue specificity and cancer. Three-dimensional culture assays provide a useful platform for dissecting these processes but, as discussed in a recent study in BMC Biology on the culture of mammary gland epithelial cells, multiple parameters that influence the model must be taken into account. PMID: 20092610 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | [Clone screening and interference efficiency of seed cells with CCL20 gene knockdown for tissue-engineered skin] Zhonghua Wai Ke Za Zhi. 2009 Apr 15;47(8):621-4 Authors: Wang LH, Peng DZ, Liu J, Zhou X, Wang Y, He SD, He B, Zheng BX, Dong ZX, Zhou GQ OBJECTIVE: To screen stable cell clones of CCL20 gene knockdown and assess their interference effects, recombinant lentivirus vectors with CCL20 gene specific shRNA were applied to infect human immortal keratinocyte line (HaCaT). METHODS: The three pHSER-CCL20-shRNA-GFP vectors (pHCG-1 and pHCG-2 were CCL20 gene specific, and pHCG-3 was used as mismatch control) have been previously constructed. The virus packaging cell line 293FT was transfected with these vectors by using CaCl2 methods to produce lectiviral particles. After the viral titers of these three harvested cell supernatants were determined by flow cytometry, HaCaT cells were transfected by these viruses and screened under the pressure of G418. The CCL20 mRNA from HaCaT cell clones and the CCL20 protein levels in the supernatants of HaCaT cell clones were detected by Real-time RT-PCR and ELISA, respectively. RESULTS: The titers of three lentiviruses were 7.08 x 10(5) transduced units (TU)/ml, 1.88 x 10(5) TU /ml and 2.08 x 10(5) TU/ml, respectively. Two HaCaT cell clones from each lectiviral vectors were obtained after G418 screening for 5 - 8 weeks. Four CCL20 gene specific clones showed stable interference effect in both Real-time RT-PCR and ELISA. The mRNA expression and protein level of CCL20 gene specific clones were down regulated significantly. CONCLUSIONS: The four human immortal keratinocyte clones with long term CCL20 gene knockdown have been screened by recombinant lentivirus vectors with CCL20 gene specific shRNA. These clones might be served as seed cells for novel tissue-engineered skin with lower rejection. PMID: 19595046 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | [Experimental study on spinal fusion induced by hBMP-4 gene modified tissue engineered bone] Zhonghua Wai Ke Za Zhi. 2009 Feb 1;47(3):197-201 Authors: Zheng ZM, Dong ZY, Kuang GM, Chen H, Lü Y, Zhang KB, Liu H, Li FB OBJECTIVE: To evaluate the efficacy of hBMP-4 gene modified tissue engineered bone graft in the enhancement of rabbit spinal fusion and find an ideal kind of substitute for the autograft bone. METHODS: Rabbit BMSCs were cultured and transfected with AAV-hBMP-4 using different MOI value. The optimal MOI value were determined by observing cell's morphology change. BMSCs were then transfected with AAV-hBMP4 and AAV-EGFP respectively, following which the transfected cells were evenly suspended in a collagen sponge I, and implanted to either side of the L5,6 intertransverse spaces posterolateral in the New Zealand rabbits to induce spinal fusion. Fourteen rabbits were randomly divided into 2 groups. Group 1: AAV-hBMP-4 transfected BMSCs in the right side (hBMP-4 side) and autograft bone in the left side. Group 2: AAV-hBMP-4 transfected BMSCs in the right side (hBMP-4 side) and AAV-EGFP transfected BMSCs in the left side (EGFP side). Radiographs and three-dimensional CT of the spine, manual palpation, gross and histological examination of the fusion masses for all the animals were performed subsequent to animals having been sacrificed at 12 weeks after surgery. RESULTS: Evaluation has been taken in 12 New Zealand rabbits delivered into 2 groups which meet the criterion after operation. Eleven in 12 implemented sides involved hBMP-4 achieved bony fusion, to which 5 in 6 autografted sides was similar. But only 2 in 6 sides in EGFP-group achieved bony fusion meanwhile. Three-dimensional CT scan and palpation also evidenced the results. Bone formation was observed obviously on specimen both in hBMP4 sides and autografted ones. EGFP-group also got bony integration, but the quantity was small. CONCLUSION: Tissue-engineered bone graft constructed from application of hBMP4 is a fine substitute for autograft. Effective enhancement of bony integration in spinal fusion surgery has been evidenced in vivo. PMID: 19563074 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | An imprinted signature helps isolate ESC-equivalent iPSCs. Cell Res. 2010 Aug 10; Authors: Lujan E, Wernig M PMID: 20697429 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Prospects for Minocycline Neuroprotection. Arch Neurol. 2010 Aug 9; Authors: Plane JM, Shen Y, Pleasure DE, Deng W Minocycline is a clinically available antibiotic and anti-inflammatory drug that also demonstrates neuroprotective properties in a variety of experimental models of neurological diseases. There have thus far been more than 300 publications on minocycline neuroprotection including a growing number of human studies. Our objective is to critically review the biological basis and translational potential of this action of minocycline on the nervous system. PMID: 20697034 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | A model for the stretch-mediated enzymatic degradation of silk fibers. J Mech Behav Biomed Mater. 2010 Oct;3(7):538-547 Authors: Kluge JA, Thurber A, Leisk GG, Kaplan DL, Luis Dorfmann A To restore physiological function through regenerative medicine, biomaterials introduced into the body must degrade at a rate that matches new tissue formation. For effective therapies, it is essential that we understand the interaction between physiological factors, such as routine mechanical loading specific to sites of implantation, and the resultant rate of material degradation. These relationships are poorly characterized at this time. We hypothesize that mechanical forces alter the rates of remodeling of biomaterials, and this impact is modulated by the concentration of enzymes and the duration of the mechanical loads encountered in situ. To test this hypothesis we subjected silk fibroin fibers to repeated cyclic loading in the presence of enzymatic degradation (either alpha-chymotrypsin or Protease XIV) and recorded the stress-strain response. Data were collected daily for a duration of 2 weeks and compared to the control cases of stretched fibers in the presence of phosphate buffered saline or non-stretched samples in the presence of enzyme alone. We observed that incubation with proteases in the absence of mechanical loads causes a reduction of the ultimate tensile strength but no change in stiffness. However, cyclic loading caused the accumulation of residual strain and softening in the material's properties. We utilize these data to formulate a mathematical model to account for residual strain and reduction of mechanical properties during silk fiber degradation. Numerical predictions are in fair agreement with experimental data. The improved understanding of the degradation phenomenon will be significant in many clinical repair cases and may be synergistic to decrease silk's mechanical properties after in vivo implantation. PMID: 20696419 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Interview with Prof. Dr. Augustinus Bader. Rejuvenation Res. 2010 Aug 9; Authors: Editor's note: The interview series in Rejuvenation Research is a unique and, I believe, highly valuable feature of the journal, giving readers insights into the thinking and motivation of some of the most influential movers and shakers in the many disciplines-not only scientific( 1-7 ) but also political,( 8 , 9 ) sociological,( 10 ) ethical,( 11 ) and more-that impinge on the crusade to defeat aging. This issue's interview features a leading academic from the world of tissue engineering and stem cells, who has enthusiastically embraced the application of those technologies to the problem of aging. Moreover, Professor Bader is highly active in the effort to birng such groups together across both national and scientific borders, as exemplified by the recent adoption of Rejuvenation Research as the official journal of the World Federation and World Virtual Institute of Regenerative Medicine, which he leads. Such efforts constitute a powerful force in stimulating high-quality communication between the field of biomedical gerontology and the many constituencies that will be affected by progress against aging-a debate that, as I( 12-22 ) and others( 23-28 ) have noted recently, is essential if we are to develop effective interventions against aging with all possible speed. PMID: 20695819 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Analysis of the Soluble Human Tooth Proteome and Its Ability to Induce Dentin/Tooth Regeneration. Tissue Eng Part A. 2010 Aug 9; Authors: Chun SY, Lee HJ, Choi YA, Kim KM, Baek SH, Park HS, Kim JY, Ahn JM, Cho JY, Cho DW, Shin HI, Park EK While the soluble proteins of human teeth consist of various extracellular matrix (ECM) and bioactive proteins, they have not yet been characterized fully. Moreover, the role they play in tooth regeneration is not clear. Analysis of the soluble proteins in human teeth by liquid chromatography-mass spectrometry (LC-MS/MS) revealed 147 different EDTA-soluble tooth proteins (ESTPs). Of these, 29 had not been shown previously to be present in human teeth. To determine their effect on the in vitro responses of dental pulp stem cells (DPSCs), DPSCs were cultured in ESTP-coated culture plates and 3-dimensional scaffolds. The ESTPs significantly enhanced DPSC odontoblast differentiation and mineralization in vitro, but had only partial effect on bone marrow stem cells or adipose tissue stem cells. To test the effect of ESTPs on in vivo dentin and tooth formation, mouse embryonic tooth-forming primordia and xenogenic murine apical bud epithelium/human DPSC composites were treated with ESTPs prior to implantation under the renal capsule of ICR mice. ESTP treatment promoted the formation of morphologically normal teeth by the tooth-forming primordium regions and enhanced the development of a regular and large dentin structure by the composites. These observations suggest that human ESTPs contain dentinogenic proteins and can promote dentin and tooth formation. PMID: 20695775 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | A novel bioengineering clinical device testing cellular homeostatic potentials to customize and monitor nutritional-related age-management interventional strategies. Rejuvenation Res. 2010 Apr-Jun;13(2-3):256-9 Authors: Mariani G, Dellaglio F, Marotta F Most devices assessing body composition harbor a number of drawbacks and hardly assess the phenomena taking place at a cellular membrane level. The present single-frequency bioelectrical potential homeostatic structure analysis (PHoSA) technology requires only a proper hands contact on fixed electrodes and determines the phase displacement between tested current and voltage by using a 50-KHz alternate sinusoidal current. This allows quick testing time with high degree of precision, sensitivity, and specificity of sectorial functional body compartments analysis. Such assessment may prove to be an integrated part of either a diagnostic workup or monitoring tool in tailoring nutritional/nutraceutical, pharmacological, and exercise activity, all being framed within a proactive, preventive, age-intervention management strategy. PMID: 20462382 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Demographic consequences of defeating aging. Rejuvenation Res. 2010 Apr-Jun;13(2-3):329-34 Authors: Gavrilov LA, Gavrilova NS A common objection against starting a large-scale biomedical war on aging is the fear of catastrophic population consequences (overpopulation). This fear is only exacerbated by the fact that no detailed demographic projections for radical life extension scenario have been conducted so far. This study explores different demographic scenarios and population projections, in order to clarify what could be the demographic consequences of a successful biomedical war on aging. A general conclusion of this study is that population changes are surprisingly slow in their response to a dramatic life extension. For example, we applied the cohort-component method of population projections to 2005 Swedish population for several scenarios of life extension and a fertility schedule observed in 2005. Even for very long 100-year projection horizon, with the most radical life extension scenario (assuming no aging at all after age 60), the total population increases by 22% only (from 9.1 to 11.0 million). Moreover, if some members of society reject to use new anti-aging technologies for some religious or any other reasons (inconvenience, non-compliance, fear of side effects, costs, etc.), then the total population size may even decrease over time. Thus, even in the case of the most radical life extension scenario, population growth could be relatively slow and may not necessarily lead to overpopulation. Therefore, the real concerns should be placed not on the threat of catastrophic population consequences (overpopulation), but rather on such potential obstacles to a success of biomedical war on aging, as scientific, organizational, and financial limitations. PMID: 20426616 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Practice of postponing human aging. Rejuvenation Res. 2010 Apr-Jun;13(2-3):356-8 Authors: Kristjuhan U People want to be wealthy, attractive, young, and healthy, and they integrate these wishes into most of their activities. As a result, aging processes are somewhat postponed in the human organism. Both average life expectancy and expected life in good health increase by 0.15-0.2 years every year in most developed countries. Studies show that using contemporary knowledge enables an increase in life expectancy up to 90 years in these countries, and much more in the future. Increases in life expectancy depend on the interest of society in these problems and on the amount of scientific research directed at postponing aging and rejuvenation. PMID: 20370496 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | Affordable rejuvenation: a prototype facility in action. Rejuvenation Res. 2010 Apr-Jun;13(2-3):350-2 Authors: Prokopov AF, Reinmuth J The Strategies for Engineered Negligible Senescence (SENS) agenda contemplates specialized centers that offer a periodic rejuvenation and biogerontological maintenance for their clients. Although high-tech interventions are still in an early research phase, well-proven natural techniques, such as various forms of caloric/nutritional restriction, physical training, and preconditioning treatments, are not unanimously embraced due to poor adherence of patients. The practicability of such interventions can be significantly improved by "engineering" them for higher efficiency and better user friendliness. We describe practical experience in developing and running a prototype facility that uses rejuvenative treatment protocols, derived from two natural life span-prolonging strategies: Intermittent calorie/nutritive restriction (ICR) and intermittent oxygen restriction (IOR). PMID: 20370490 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | The Drosophila planar polarity proteins inturned and multiple wing hairs interact physically and function together. Genetics. 2010 Jun;185(2):549-58 Authors: Lu Q, Yan J, Adler PN The conserved frizzled (fz) pathway regulates planar cell polarity in both vertebrate and invertebrate animals. This pathway has been most intensively studied in the wing of Drosophila, where the proteins encoded by pathway genes all accumulate asymmetrically. Upstream members of the pathway accumulate on the proximal, distal, or both cell edges in the vicinity of the adherens junction. More downstream components including Inturned and Multiple Wing Hairs accumulate on the proximal side of wing cells prior to hair initiation. The Mwh protein differs from other members of the pathway in also accumulating in growing hairs. Here we show that the two Mwh accumulation patterns are under different genetic control with the early proximal accumulation being regulated by the fz pathway and the latter hair accumulation being largely independent of the pathway. We also establish recruitment by proximally localized Inturned to be a putative mechanism for the localization of Mwh to the proximal side of wing cells. Genetically inturned (in) acts upstream of mwh (mwh) and is required for the proximal localization of Mwh. We show that Mwh can bind to and co-immunoprecipitate with Inturned. We also show that these two proteins can function in close juxtaposition in vivo. An InMwh fusion protein provided complete rescue activity for both in and mwh mutations. The fusion protein localized to the proximal side of wing cells prior to hair formation and in growing hairs as expected if protein localization is a key for the function of these proteins. PMID: 20351219 [PubMed - indexed for MEDLINE] | | | | | | | | | | |  |
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