|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | The closed-door machinations involving the election of a new chair of the California stem cell agency raise important policy questions about the conduct of the agency, its openness and whether the structure of the board and chairman is in the best public interest.
Last year, the Little Hoover Commission, the state's good government agency, documented many of those problems in its 88-page | | | | | | | | | | | | | | | | | | | | | | | | CIRM Chairman Robert Klein tonight issued an unequivocal statement that he would seek re-election to his post, declaring that he was needed to provide "continuity" to the $3 billion enterprise for the next 12 months.
Klein said he accepted the nomination and would "work with the (CIRM) board and the constitutional officers to identify candidates...to succeed me" within the next year.
Klein's | | | | | | | | | | | | | | | | | | | | | | | | | Reporter Ron Leuty of the San Francisco Business Times has wrapped up the CIRM election events of the day in a piece that can be found here. | | | | | | | | | | | | | | | | | | | | | | | | In a statement made in connection with his re-nomination as chairman of the California stem cell agency, Robert Klein said today he wanted "to continue to build" on the state's stem cell research record.
But did he say he would accept re-nomination?
CIRM's chief communications officer, Don Gibbons, pointed us to the statement when we asked whether Klein planned to accept re-nomination.
The | | | | | | | | | | | | | | | | | | | | | | | | Republican California Gov. Arnold Schwarzenegger today nominated Robert Klein for a second term as chairman of the California stem cell agency after Klein's attempt to hand pick his successor collapsed amid questions about the integrity of the process.
Reporter Ron Leuty of the San Francisco Business Times was the first to report Klein's re-nomination.
Also nominating Klein for another term | | | | | | | | | | | | | | | | | | | | | | | | Efforts by CIRM Chairman Robert Klein to engineer the election of Alan Bernstein as his successor at the $3 billion California stem cell agency collapsed today when Bernstein withdrew from the race, the California Stem Cell Report has been told.
The move followed yesterday's disclosure (see here and here) of a closed-door meeting Sunday at a Portola Valley restaurant attended by only five of | | | | | | | | | | | | | | | | | | | | | | | | The ruckus over selection of a new chairman for the California stem cell agency this morning drew the rare attention of the Los Angeles Times, the state's largest circulation newspaper.
And it wasn't the kind of attention that CIRM is looking for.
Reporter Jack Dolan mentioned a "possible conflict of interest" involving Alan Bernstein, a candidate backed by outgoing chairman Robert Klein, and | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine: Self-directed articular resurfacing: a new paradigm? Nat Rev Rheumatol. 2010 Dec;6(12):677-8 Authors: Grande DA, Sgaglione NA PMID: 21119714 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Generation of HIV-1 Resistant and Functional Macrophages From Hematopoietic Stem Cell-derived Induced Pluripotent Stem Cells. Mol Ther. 2010 Nov 30; Authors: Kambal A, Mitchell G, Cary W, Gruenloh W, Jung Y, Kalomoiris S, Nacey C, McGee J, Lindsey M, Fury B, Bauer G, Nolta JA, Anderson JS Induced pluripotent stem cells (iPSCs) have radically advanced the field of regenerative medicine by making possible the production of patient-specific pluripotent stem cells from adult individuals. By developing iPSCs to treat HIV, there is the potential for generating a continuous supply of therapeutic cells for transplantation into HIV-infected patients. In this study, we have used human hematopoietic stem cells (HSCs) to generate anti-HIV gene expressing iPSCs for HIV gene therapy. HSCs were dedifferentiated into continuously growing iPSC lines with four reprogramming factors and a combination anti-HIV lentiviral vector containing a CCR5 short hairpin RNA (shRNA) and a human/rhesus chimeric TRIM5α gene. Upon directed differentiation of the anti-HIV iPSCs toward the hematopoietic lineage, a robust quantity of colony-forming CD133(+) HSCs were obtained. These cells were further differentiated into functional end-stage macrophages which displayed a normal phenotypic profile. Upon viral challenge, the anti-HIV iPSC-derived macrophages exhibited strong protection from HIV-1 infection. Here, we demonstrate the ability of iPSCs to develop into HIV-1 resistant immune cells and highlight the potential use of iPSCs for HIV gene and cellular therapies. PMID: 21119622 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets. Proc Natl Acad Sci U S A. 2010 Nov 30; Authors: Ooi AG, Sahoo D, Adorno M, Wang Y, Weissman IL, Park CY MicroRNAs profoundly impact hematopoietic cells by regulating progenitor cell-fate decisions, as well as mature immune effector function. However to date, microRNAs that regulate hematopoietic stem cell (HSC) function have been less well characterized. Here we show that microRNA-125b (miR-125b) is highly expressed in HSCs and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1(lo)CD34(-) lymphoid-balanced and the Slamf1(neg)CD34(-) lymphoid-biased cell subsets within the multipotent HSC (CD34-KLS) fraction. Mature peripheral blood cells derived from the miR-125b-overexpressing HSC are skewed toward the lymphoid lineage. Consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoid-biased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13. The antiapoptotic effect of miR-125b is more pronounced in the lymphoid-biased HSC subset because of their intrinsic higher baseline levels of apoptosis. These effects of miR-125b are associated with the development of lymphoproliferative disease, marked by expansion of CD8(+) T lymphocytes. Taken together, these data reveal that miR-125b regulates HSC survival and can promote lymphoid-fate decisions at the level of the HSC by preferentially expanding lymphoid-balanced and lymphoid-biased HSC. PMID: 21118986 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A [polycation:heparin] complex releases growth factors with enhanced bioactivity. J Control Release. 2010 Nov 27; Authors: Chu H, Johnson NR, Mason NS, Wang Y Growth factors are potent molecules that regulate cell functions including survival, self renewal, differentiation and proliferation. High-efficacy delivery of growth factors will be a powerful tool for regenerative medicine. Decades of intense research have significantly advanced the field of controlled delivery. There is, however, still a great unmet need for new methods that can improve overall efficacy of growth-factor delivery. Here, we report a new growth factor delivery vehicle formed by self assembly of heparin and a biocompatible polycation, poly(ethylene argininylaspartate diglyceride) (PEAD). Of the many heparin-binding growth factors, we chose FGF-2 and NGF to demonstrate the potential of the [PEAD:heparin] delivery vehicle. The delivery vehicle incorporates both growth factors with high efficiency, controls their release, maintains the bioactivity of FGF-2 and increases the bioactivity of NGF relative to bolus delivery. [PEAD:heparin] appears to be a promising delivery matrix for many heparin-binding growth factors and may lead to efficient growth factor delivery for a variety of diseases and disabilities. PMID: 21118705 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Thin Films of Functionalized Multiwalled Carbon Nanotubes as Suitable Scaffold Materials for Stem Cells Proliferation and Bone Formation. ACS Nano. 2010 Nov 30; Authors: Nayak TR, Jian L, Phua LC, Ho HK, Ren Y, Pastorin G In the field of regenerative medicine, human mesenchymal stem cells envisage extremely promising applications, due to their ability to differentiate into a wide range of connective tissue species on the basis of the substrate on which they grow. For the first time ever reported, we investigated the effects of a thin film of pegylated multiwalled carbon nanotubes spray dried onto preheated coverslips in terms of their ability to influence human mesenchymal stem cells' proliferation, morphology, and final differentiation into osteoblasts. Results clearly indicated that the homogeneous layer of functionalized nanotubes did not show any cytotoxicity and accelerated cell differentiation to a higher extent than carboxylated nanotubes or uncoated coverslips, by creating a more viable microenvironment for stem cells. Interestingly, cell differentiation occurred even in the absence of additional biochemical inducing agents, as evidenced by multiple independent criteria at the transcriptional, protein expression, and functional levels. Taken together, these findings suggest that functionalized carbon nanotubes represent a suitable scaffold toward a very selective differentiation into bone. PMID: 21117641 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Current therapies for the soluble lysosomal forms of neuronal ceroid lipofuscinosis. Biochem Soc Trans. 2010 Dec 1;38(6):1484-8 Authors: Wong AM, Rahim AA, Waddington SN, Cooper JD The NCLs (neuronal ceroid lipofuscinoses) are the most common inherited paediatric neurodegenerative disorder. Although genetically distinct, NCLs can be broadly divided into two categories: one in which the mutation results in a defect in a transmembrane protein, and the other where the defect lies in a soluble lysosomal enzyme. A number of therapeutic approaches are applicable to the soluble lysosomal forms of NCL based on the phenomenon of cross-correction, whereby the ubiquitously expressed mannose 6-phosphate/IGF (insulin-like growth factor) II receptor provides an avenue for endocytosis, trafficking and lysosomal processing of extracellularly delivered enzyme. The present review discusses therapeutic utilization of cross-correction by enzyme-replacement therapy, gene therapy and stem cell therapy for the NCLs, along with an overview of the recent progress in translating these treatments into the clinic. PMID: 21118112 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | In Vitro and In Vivo Cardiomyogenic Differentiation of Amniotic Fluid Stem Cells. Stem Cell Rev. 2010 Dec 1; Authors: Bollini S, Pozzobon M, Nobles M, Riegler J, Dong X, Piccoli M, Chiavegato A, Price AN, Ghionzoli M, Cheung KK, Cabrelle A, O'Mahoney PR, Cozzi E, Sartore S, Tinker A, Lythgoe MF, De Coppi P Cell therapy has developed as a complementary treatment for myocardial regeneration. While both autologous and allogeneic uses have been advocated, the ideal candidate has not been identified yet. Amniotic fluid-derived stem (AFS) cells are potentially a promising resource for cell therapy and tissue engineering of myocardial injuries. However, no information is available regarding their use in an allogeneic context. c-kit-sorted, GFP-positive rat AFS (GFP-rAFS) cells and neonatal rat cardiomyocytes (rCMs) were characterized by cytocentrifugation and flow cytometry for the expression of mesenchymal, embryonic and cell lineage-specific antigens. The activation of the myocardial gene program in GFP-rAFS cells was induced by co-culture with rCMs. The stem cell differentiation was evaluated using immunofluorescence, RT-PCR and single cell electrophysiology. The in vivo potential of Endorem-labeled GFP-rAFS cells for myocardial repair was studied by transplantation in the heart of animals with ischemia/reperfusion injury (I/R), monitored by magnetic resonance imaging (MRI). Three weeks after injection a small number of GFP-rAFS cells acquired an endothelial or smooth muscle phenotype and to a lesser extent CMs. Despite the low GFP-rAFS cells count in the heart, there was still an improvement of ejection fraction as measured by MRI. rAFS cells have the in vitro propensity to acquire a cardiomyogenic phenotype and to preserve cardiac function, even if their potential may be limited by poor survival in an allogeneic setting. PMID: 21120638 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Thermoresponsible Cell Adhesion/Detachment on Transparent Nanocomposite Films Consisting of Poly(2-methoxyethyl acrylate) and Clay. J Biomater Sci Polym Ed. 2010 Nov 30; Authors: Haraguchi K, Masatoshi S, Kotobuki N, Murata K Soft, transparent and mechanically tough nanocomposite (M-NC) films composed of poly(2-methoxyethyl acrylate) (PMEA) and inorganic clay (hectorite) were studied as substrates for a living cell harvest system. It was found that five cell types could all be cultivated to confluence on the surface of M-NCn films with clay content (n=10-23 wt%), although the cells hardly cultivated on the surface of chemically-cross-linked PMEA and linear PMEA films. Further, it was found that the cells cultured on the surfaces of M-NC films can be detached, without any enzymatic digestion, by decreasing the medium temperature and/or simultaneously using gentle pipetting. The detached cell was obtained as a single cell or a contiguous cell sheet, both of which were viable and recultured. From the compositions and surface properties, it was estimated that the cell culture and subsequent cell detachment were attributed to the unique PMEA/clay network. The new soft nanocomposite is potentially a very promising substrate for tissue engineering. PMID: 21118632 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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