|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | In his bid to be re-elected, the chairman of the $3 billion California stem cell agency, Robert Klein has issued a financial warning to CIRM directors that is distinctly at odds with what the state treasurer's has told him.
In response to questions from the California Stem Cell Report, Tom Dresslar, spokesman for state Treasurer Bill Lockyer, provided an account that differs in major ways with | | | | | | | | | | | | | | | | | | | | | | | | Reporter Ron Leuty of the San Francisco Business Times today offered himself up as a candidate for chair of the $3 billion stem cell agency. Leuty's "statement of candidacy" included this paragraph:
"I am a resident of California — if that matters — and I have been in the hospital, which I believe would fulfill the requirement that the ICOC Chair be a patient advocate. One time after knee surgery | | | | | | | | | | | | | | | | | | | | | | | | Former Hollywood studio chief and CIRM Director Sherry Lansing today endorsed Robert Klein for re-election as chairman of the $3 billion California stem cell agency.
In a two-paragraph statement posted on the CIRM Web site, Lansing said she enthusiastically supported Klein as well as the re-election of Art Torres and Duane Roth as co vice chairs.
No other members of the CIRM board have posted | | | | | | | | | | | | | | | | | | | | | | | | Less than two weeks ago, CIRM Chairman Robert Klein told directors of the California stem cell agency that its financial situation was rosy and no problems existed with its bond financing, its only source of cash.
His statements on Dec. 3 stand in sharp contrast to his election eve warning today that the agency must act swiftly to stave off a looming funding problem.
Klein made his comments at | | | | | | | | | | | | | | | | | | | | | | | | CIRM Chairman Robert Klein today sounded an urgent, financial alarm in his bid to be re-elected to a new term at the $3 billion California stem cell agency.
In a "statement of candidacy" on the CIRM Web site, Klein indicated he was needed at the agency to handle a sudden, new quasi-crisis that requires action next month. And in an effort to make it easy for directors to choose him at their | | | | | | | | | | | | | | | | | | | | | | | | | Epigenetic alteration of the NF-κB-inducing kinase (NIK) gene is involved in enhanced NIK expression in basal-like breast cancer. Cancer Sci. 2010 Nov;101(11):2391-7 Authors: Yamamoto M, Ito T, Shimizu T, Ishida T, Semba K, Watanabe S, Yamaguchi N, Inoue J Basal-like breast cancers are triple-negative (estrogen receptor negative, progesterone receptor negative, erythroblastic leukemia viral oncogene homolog 2 (ERBB2) negative) tumors with an aggressive clinical behavior that lacks effective molecular targets for therapy. We reported previously that the basal-like subtype cell lines display high constitutive nuclear factor (NF)-κB activation, whose inhibition in the basal-like subtypes suppressed their proliferation. Moreover, NF-κB-inducing kinase (NIK) is involved in the constitutive NF-κB activation. Here, we report that enhanced NIK expression, which is exclusively observed in the basal-like subtype rather than the luminal-like subtype or non-tumorigenic mammary epithelial cells, is caused by epigenetic alteration of the NIK gene. The stability of NIK mRNA and transcriptional activity driven by the NIK promoter are similar in the basal-like and luminal-like subtypes. However, histone H3 acetylation levels were up-regulated in the basal-like subtype. Furthermore, treatment of the luminal-like subtype with a histone deacetylase inhibitor, valproic acid, significantly increased NIK expression. Although DNA methylation of the NIK locus was not detected, NIK expression also increased when the luminal-like subtype was treated with 5-azacytidine, which inhibits histone H3-Lys-9 dimethylation in addition to DNA methylation. Taken together, these results suggest that the closed chromatin structure mediated by histone H3 methylation and deacetylation suppresses NIK expression in the luminal-like subtype, whereas disruption of these suppression mechanisms leads to enhanced NIK expression and the constitutive NF-κB activation in the basal-like subtype. Thus, NIK and genes induced by the NIK-mediated constitutive NF-κB activation could be therapeutic targets of basal-like breast cancer. PMID: 20735436 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | New surgical approach to lichen sclerosus of the vulva: the role of adipose-derived mesenchymal cells and platelet-rich plasma in tissue regeneration. Plast Reconstr Surg. 2010 Oct;126(4):210e-211e Authors: Casabona F, Priano V, Vallerino V, Cogliandro A, Lavagnino G PMID: 20885230 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Hematopoietic stem cells exhibit a specific ABC transporter gene expression profile clearly distinct from other stem cells. BMC Pharmacol. 2010;10:12 Authors: Tang L, Bergevoet SM, Gilissen C, de Witte T, Jansen JH, van der Reijden BA, Raymakers RA ATP-binding cassette (ABC) transporters protect cells against unrelated (toxic) substances by pumping them across cell membranes. Earlier we showed that many ABC transporters are highly expressed in hematopoietic stem cells (HSCs) compared to more committed progenitor cells. The ABC transporter expression signature may guarantee lifelong protection of HSCs but may also preserve stem cell integrity by extrusion of agents that trigger their differentiation. Here we have studied whether non-hematopoietic stem cells (non-HSCs) exhibit a similar ABC transporter expression signature as HSCs. PMID: 20836839 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Myocardial regeneration potential of adipose tissue-derived stem cells. Biochem Biophys Res Commun. 2010 Oct 22;401(3):321-6 Authors: Bai X, Alt E Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying mechanisms for beneficial effect on cardiac function, and safety issues. PMID: 20833143 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Influence of allogenic and autologic multipotent stromal cells of adipose tissue upon bone tissue regeneration in the rabbit mandible angle defect]. Stomatologiia (Mosk). 2010;89(1):23-9 Authors: Cherniaev SE, Kiseleva EV, Grigor'ian AS, Volozhin AI Reconstructive surgery often collides with complicated task of defect recovery in the situation of deficit of maxillofacial skeleton tissues, that leads to necessary search of accessible cells source with osteogenic potentials and proper substrate for cell transplantation. In the study the regeneratory potential of stromal cells of adipose tissue was tested in the rabbit model of mandible through angle defect. Cells of allogenic and autologic nature stimulated reparative osteogenesis but their influence upon bone matrix maturation was different. When the construction with allogenic cells was transplanted reaction of its rejection was not detected on histological level. PMID: 20436405 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Use of mesenchymal stem cells for reparative processes activation in bone jaw tissue in experimental conditions]. Stomatologiia (Mosk). 2010;89(1):10-4 Authors: Volozhin AI, Vasil'ev AIu, Malyginov NN, Bulanova IM, Grigor''ian AS, Kiseleva EV, Cherniaev SE, Tarasenko IV In experiment on 12 Chinchilla rabbits dynamics of reparative regeneration was studied at the terms 2 and 4 months. Bone defect in mandible corner was closed by osteoplastic material Gapkol which was covered from inside by allogenic or autologic stem cells received from rabbit adipose tissue. The results of the ray tracing methods of study were verified by SEM and histological methods. PMID: 20436403 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | UK science dealt lighter blow than other sectors in budget cuts. Nat Med. 2010 Nov;16(11):1173 Authors: Evans J PMID: 21052057 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Nanomedicine: small size, big stakes]. Rev Prat. 2010 Sep 20;60(7):896-7 Authors: Dab W PMID: 21033478 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The magic and mystery of miR-21. J Clin Invest. 2010 Nov 1;120(11):3817-9 Authors: Morrisey EE MicroRNAs (miRNAs) are potent regulators of mRNA stability and thereby protein expression. As such, miRNAs have become of interest as possible therapeutics and/or therapeutic targets. In this context, small complementary miRNA sequences known as antagomirs could be used to inhibit miRNA activity, while miRNA mimics could confer gain-of-function activity. However, a note of caution is sounded by Patrick et al. in this issue of the JCI, as they show that although recent reports have suggested that an miR-21 antagomir might be therapeutically useful in preventing heart failure in mice, genetic deletion of miR-21 does not confer a similar phenotype, suggesting possible confounding factors that are only now beginning to be revealed in the techniques used to study miRNA biology. PMID: 20978356 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Revival of the placenta]. Rev Med Suisse. 2010 Sep 8;6(261):1684-5 Authors: Nau JY PMID: 20939405 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | A 15-year clinical comparative study of the cumulative survival rate of cast metal core and resin core restorations luted with adhesive resin cement. Int J Prosthodont. 2010 Sep-Oct;23(5):397-405 Authors: Hikasa T, Matsuka Y, Mine A, Minakuchi H, Hara ES, Van Meerbeek B, Yatani H, Kuboki T The aim of this study was to compare the core survival rates (CSRs) of cast metal versus resin core restorations luted with adhesive resin cement, as well as to determine the risk factors for core failure. PMID: 20859553 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Allogenic fetal membrane-derived mesenchymal stem cells contribute to renal repair in experimental glomerulonephritis. Am J Physiol Renal Physiol. 2010 Nov;299(5):F1004-13 Authors: Tsuda H, Yamahara K, Ishikane S, Otani K, Nakamura A, Sawai K, Ichimaru N, Sada M, Taguchi A, Hosoda H, Tsuji M, Kawachi H, Horio M, Isaka Y, Kangawa K, Takahara S, Ikeda T Mesenchymal stem cells (MSC) have been reported to be an attractive therapeutic cell source for the treatment of renal diseases. Recently, we reported that transplantation of allogenic fetal membrane-derived MSC (FM-MSC), which are available noninvasively in large amounts, had a therapeutic effect on a hindlimb ischemia model (Ishikane S, Ohnishi S, Yamahara K, Sada M, Harada K, Mishima K, Iwasaki K, Fujiwara M, Kitamura S, Nagaya N, Ikeda T. Stem Cells 26: 2625-2633, 2008). Here, we investigated whether allogenic FM-MSC administration could ameliorate renal injury in experimental glomerulonephritis. Lewis rats with anti-Thy1 nephritis intravenously received FM-MSC obtained from major histocompatibility complex-mismatched ACI rats (FM-MSC group) or a PBS (PBS group). Nephritic rats exhibited an increased urinary protein excretion in the PBS group, whereas the FM-MSC group rats had a significantly lower level of increase (P < 0.05 vs. PBS group). FM-MSC transplantation significantly reduced activated mesangial cell (MC) proliferation, glomerular monocyte/macrophage infiltration, mesangial matrix accumulation, as well as the glomerular expression of inflammatory or extracellular matrix-related genes including TNF-α, monocyte chemoattractant protein 1 (MCP-1), type I collagen, TGF-β, type 1 plasminogen activator inhibitor (PAI-1) (P < 0.05 vs. PBS group). In vitro, FM-MSC-derived conditioned medium significantly attenuated the expression of TNF-α and MCP-1 in rat MC through a prostaglandin E(2)-dependent mechanism. These data suggest that transplanted FM-MSC contributed to the healing process in injured kidney tissue by producing paracrine factors. Our results indicate that allogenic FM-MSC transplantation is a potent therapeutic strategy for the treatment of acute glomerulonephritis. PMID: 20739390 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The demographic and biomedical case for late-life interventions in aging. Sci Transl Med. 2010 Jul 14;2(40):40cm21 Authors: Rae MJ, Butler RN, Campisi J, de Grey AD, Finch CE, Gough M, Martin GM, Vijg J, Perrott KM, Logan BJ The social and medical costs of the biological aging process are high and will rise rapidly in coming decades, creating an enormous challenge to societies worldwide. In recent decades, researchers have expanded their understanding of the underlying deleterious structural and physiological changes (aging damage) that underlie the progressive functional impairments, declining health, and rising mortality of aging humans and other organisms and have been able to intervene in the process in model organisms, even late in life. To preempt a global aging crisis, we advocate an ambitious global initiative to translate these findings into interventions for aging humans, using three complementary approaches to retard, arrest, and even reverse aging damage, extending and even restoring the period of youthful health and functionality of older people. PMID: 20630854 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The enigma that is the nucleus pulposus cell: the search goes on. Arthritis Res Ther. 2010;12(3):118 Authors: Erwin WM The development of an effective treatment for degenerative disc disease has been hampered for many years by what seems a fundamental problem; what exactly defines a nucleus pulposus (NP) cell? The paper by Gilson and colleagues elegantly re-opens the debate concerning the lineage and identity of NP cells that are alike yet different from chondrocytes. As we pursue novel investigations and treatment strategies for degenerative disc disease, how do we isolate these unique cells and what is the role of the primordial notochordal cell that may well linger within the NP far longer and perhaps in a different phenotypic appearance than previously thought? The paper by Gilson and colleagues that is the subject of the present editorial presents compelling data concerning the heterogeneity of the cells of the NP, and their origin, development, maturation and function. PMID: 20587085 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Allowing innovative stem cell-based therapies outside of clinical trials: ethical and policy challenges. J Law Med Ethics. 2010;38(2):277-85 Authors: Hyun I This paper discusses exceptional circumstances under which patients outside of clinical trials are likely to receive innovative stem cell-based interventions. These circumstances involve: (1) stem cell interventions not initially amenable to a clinical trials approach; (2) expanded access to investigational stem cell products ("compassionate use"); and (3) off-label uses of FDA approved stem cell products. This paper proposes a new approach to regulating these exceptional cases. PMID: 20579251 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Brave pioneers or clinical cowboys? Cell Stem Cell. 2010 Jun 4;6(6):504-5 Authors: Davison AC PMID: 20578343 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Stepping stones on solid ground. Cell Stem Cell. 2010 Jun 4;6(6):493 Authors: Sweet DJ PMID: 20569680 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Transplant of GABAergic precursors restores hippocampal inhibitory function in a mouse model of seizure susceptibility. Cell Transplant. 2010;19(5):549-64 Authors: Zipancic I, Calcagnotto ME, Piquer-Gil M, Mello LE, Alvarez-Dolado M Defects in GABAergic function can cause epilepsy. In the last years, cell-based therapies have attempted to correct these defects with disparate success on animal models of epilepsy. Recently, we demonstrated that medial ganglionic eminence (MGE)-derived cells grafted into the neonatal normal brain migrate and differentiate into functional mature GABAergic interneurons. These cells are able to modulate the local level of GABA-mediated synaptic inhibition, which suggests their suitability for cell-based therapies. However, it is unclear whether they can integrate in the host circuitry and rescue the loss of inhibition in pathological conditions. Thus, as proof of principle, we grafted MGE-derived cells into a mouse model of seizure susceptibility caused by specific elimination of GABAergic interneuron subpopulations in the mouse hippocampus after injection of the neurotoxic saporin conjugated to substance P (SSP-Sap). This ablation was associated with significant decrease in inhibitory postsynaptic currents (IPSC) on CA1 pyramidal cells and increased seizure susceptibility induced by pentylenetetrazol (PTZ). Grafting of GFP(+) MGE-derived cells in SSP-Sap-treated mice repopulates the hippocampal ablated zone with cells expressing molecular markers of mature interneurons. Interestingly, IPSC kinetics on CA1 pyramidal cells of ablated hippocampus significantly increased after transplantation, reaching levels similar to the normal mice. More importantly, this was associated with reduction in seizure severity and decrease in postseizure mortality induced by PTZ. Our data show that MGE-derived cells fulfill most of the requirements for an appropriate cell-based therapy, and indicate their suitability for neurological conditions where a modulation of synaptic inhibition is needed, such as epilepsy. PMID: 20144261 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | In vivo evaluation of acellular human dermis for abdominal wall repair. J Biomed Mater Res A. 2010 Jun 15;93(4):1527-38 Authors: Eberli D, Rodriguez S, Atala A, Yoo JJ Limitations of synthetic biomaterials for abdominal wall repair have led investigators to seek naturally derived matrices, such as human acellular dermis, because of their excellent biocompatibility and their ability to naturally interface with host tissues with minimal tissue response. In this study, we investigated two different biomaterials derived from human dermis (FlexHD acellular dermis and FlexHD acellular dermis-thick) in a rabbit abdominal hernia repair model. One quarter of the abdominal wall was replaced with each biomaterial, and the animals were followed for up to 24 weeks. Rabbit hernias repaired with AlloDerm, a commercially available acellular dermal matrix, and sham operated animals served as controls. Retrieved samples of these implants were assessed grossly and histologically. Collagen production measurements and tension studies were performed. FlexHD acellular dermis, FlexHD acellular dermis-thick, and AlloDerm maintained their strength in the rabbit hernia repair model with no incidence of hernia formation or bowel adhesion. The exact size measurements at 24 weeks were 217.0 +/- 20.9% for FlexHD acellular dermis, 200.8 +/- 23.5% for FlexHD acellular dermis-thick, and 209.7 +/- 32.9% for AlloDerm. Macroscopic and microscopic evaluation showed excellent integration and tissue formation. All biomaterials studied harbored cells that produced new collagen fibers, and a six-fold increase in these fibers was observed at 24 weeks. This study shows that acellular biomaterials derived from human dermis are suitable for abdominal hernia repair. PMID: 20014294 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | In vitro uptake of amphiphilic, hydrogel nanoparticles by J774A.1 cells. J Biomed Mater Res A. 2010 Jun 15;93(4):1557-65 Authors: Missirlis D, Hubbell JA We here report improved synthesis and in vitro interactions of amphiphilic hydrogel nanoparticles with the macrophage cell line J774A.1. Nanoparticles comprising dispersed hydrophobic nanodomains of poly(propylene glycol) within a continuous phase of hydrophilic poly (ethylene glycol) (PEG) were prepared via inverse emulsion crosslinking polymerization, using acrylated PEG and Pluronic F127 as macromonomer blocks. Functionality and fluorescent labeling were achieved through incorporation of reactive comonomers and a posteriori reaction with fluorescein, respectively. When introduced to a static cell culture of adhered J774A.1 macrophages, the cells internalized these hydrogel nanoparticles in a dose- and time- dependent manner through clathrin-mediated and other pathways. Amphiphilic nanoparticle uptake was however dramatically lower than that of a model system (Fluospheres) and similar to PEG-coated colloids reported in the literature, which are considered "stealth." Our findings support the potential of the nanoparticles presented here as long-circulating drug carriers. PMID: 20014289 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | The genetics of frontotemporal dementia. Handb Clin Neurol. 2008;89:383-92 Authors: Pickering-Brown S, Hutton M PMID: 18631762 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | The San Francisco Business Times late yesterday carried a story on the "strong" recommendation by the state's top fiscal officer to cancel tomorrow's scheduled election of a new chairman of the California stem cell agency.
You can find the article by Ron Leuty here. | | | | | | | | | | | | | | | | | | | | | | | | Fans of the editorial pages of the leading newspaper in California's capital this morning read a piece denouncing the "shenanigans" of the chair of the state's $3 billion stem cell agency, Robert Klein, and urging him to step aside.
The op-ed article in The Sacramento Bee was written by John M. Simpson, stem cell project director for Consumer Watchdog of Santa Monica, Ca., a longtime observer | | | | | | | | | | | | | | | | | | | | | | | | Another member of the governing board of the $3 billion California stem cell agency today questioned a letter from 11 leading stem cell scientists supporting the re-election of Robert Klein as chairman.
Francisco Prieto, a Sacramento physician, commented on remarks by David Serrano Sewell, a CIRM board member and San Francisco deputy city attorney, in the "11 Scientists" item earler today. | | | | | | | | | |  | |  | |  |
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