|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | Tom Okarma may be out as Geron's CEO but he has a nifty cushion to ease the pain.
Reporter Ron Leuty of the San Francisco Business Times has reported that the onetime head of the Menlo Park stem cell firm could receive up to $1.3 million, including $802,500 in severance pay, as part of an agreement with the firm.
The package consists of consulting fees, reimbursement of legal fees, health | | | | | | | | | | | | | | | | | | | | | | | | | Adult Human Adipose Tissue Contains Several Types of Multipotent Cells. J Cardiovasc Transl Res. 2011 Feb 15; Authors: Tallone T, Realini C, Böhmler A, Kornfeld C, Vassalli G, Moccetti T, Bardelli S, Soldati G Multipotent mesenchymal stromal cells (MSCs) are a type of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their pluripotency and possible clinical applications have raised hopes and interest in MSCs. In an attempt to unify the terminology and the criteria to label a cell as MSC, in 2006 the International Society for Cellular Therapy (ISCT) proposed a standard set of rules to define the identity of these cells. However, MSCs are still extracted from different tissues, by diverse isolation protocols, are cultured and expanded in different media and conditions. All these variables may have profound effects on the selection of cell types and the composition of heterogeneous subpopulations, on the selective expansion of specific cell populations with totally different potentials and ergo, on the long-term fate of the cells upon in vitro culture. Therefore, specific molecular and cellular markers that identify MSCs subsets as well as standardization of expansion protocols for these cells are urgently needed. Here, we briefly discuss new useful markers and recent data supporting the rapidly emerging concept that many different types of progenitor cells are found in close association with blood vessels. This knowledge may promote the necessary technical improvements required to reduce variability and promote higher efficacy and safety when isolating and expanding these cells for therapeutic use. In the light of the discussed data, particularly the identification of new markers, and advances in the understanding of fundamental MSC biology, we also suggest a revision of the 2006 ISCT criteria. PMID: 21327755 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | Nature magazine's blog, Spoonful of Medicine, yesterday carried an item on selection of a chair for the $3 billion California stem cell agency to replace Robert Klein, who has headed the enterprise since 2004.
In her piece, Michelle Pflumm covered ground that was familiar to readers of the California Stem Cell Report, but offered additional material with interesting perspectives. The headline | | | | | | | | | | | | | | | | | | | | | | | | | Long-term Regulation of Genetically Modified Primary Hematopoietic Cells in Dogs. Mol Ther. 2011 Feb 15; Authors: Okazuka K, Beard BC, Emery DW, Schwarzwaelder K, Spector MR, Sale GE, von Kalle C, Kiem HP, Blau CA We report long-term results from a large animal model of in vivo selection. Nine years ago, we transplanted two dogs (E900 and E958) with autologous marrow CD34(+) cells that had been transduced with a gammaretrovirus vector encoding a conditionally activatable derivative of the thrombopoietin receptor. Receptor activation through administration of a chemical inducer of dimerization (CID) (AP20187 or AP1903) confers a growth advantage. We previously reported responses to two 30-day intravenous (i.v.) courses of AP20187 administered within the first 8 months post-transplantation. We now report responses to 5-day subcutaneous (s.c.) courses of AP20187 or AP1903 at months 14, 90, and 93 (E900), or month 18 (E958), after transplantation. Long-term monitoring showed no rise in transduced cells in the absence of drug. Retroviral insertion site analysis showed that 4 of 6 (E958) and 5 of 12 (E900) transduced hematopoietic cell clones persisted lifelong. Both dogs were euthanized for reasons unrelated to the gene therapy treatment at 8 years 11 months (E958) and 11 years 1 month (E900) of age. Three clones from E900 remained detectable in each of two secondary recipients, one of which was treated with, and responded to, AP1903. Our results demonstrate the feasibility of safely regulating genetically engineered hematopoietic cells over many years. PMID: 21326218 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Long non-coding RNAs: Guardians of development. Differentiation. 2010 Nov-Dec;80(4-5):175-83 Authors: van Leeuwen S, Mikkers H Two decades ago, the existence of long non-coding RNAs (lncRNAs) was discovered. In the following genomics era more transcribed non-coding genomic regions were identified. These were initially regarded as transcriptional noise and did not receive a lot of attention. Emerging data on several of these long non-coding transcripts have refuted this hypothesis by demonstrating that non-coding RNAs (ncRNAs) are important for regulating transcription and cell signaling. A special subset of the lncRNAs affecting gene transcription appears to orchestrate major developmental programs. Here, we discuss the mechanisms by which lncRNAs regulate transcription, and review the evidence that links this class of lncRNAs to a role in development. PMID: 20705382 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Gene Editing of Human Embryonic Stem Cells via an Engineered Baculoviral Vector Carrying Zinc-finger Nucleases. Mol Ther. 2011 Feb 15; Authors: Lei Y, Lee CL, Joo KI, Zarzar J, Liu Y, Dai B, Fox V, Wang P Human embryonic stem (hES) cells are renewable cell sources that have potential applications in regenerative medicine. The development of technologies to produce permanent and site-specific genome modifications is in demand to achieve future medical implementation of hES cells. We report herein that a baculoviral vector (BV) system carrying zinc-finger nucleases (ZFNs) can successfully modify the hES cell genome. BV-mediated transient expression of ZFNs specifically disrupted the CCR5 locus in transduced cells and the modified cells exhibited resistance to HIV-1 transduction. To convert the BV to a gene targeting vector, a DNA donor template and ZFNs were incorporated into the vector. These hybrid vectors yielded permanent site-specific gene addition in both immortalized human cell lines (10%) and hES cells (5%). Modified hES cells were both karyotypically normal and pluripotent. These results suggest that this baculoviral delivery system can be engineered for site-specific genetic manipulation in hES cells. PMID: 21326219 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Synthesis and characterization of nanoscale-hydroxyapatite-copper for antimicrobial activity towards bone tissue engineering applications. J Biomed Nanotechnol. 2010 Aug;6(4):333-9 Authors: Sahithi K, Swetha M, Prabaharan M, Moorthi A, Saranya N, Ramasamy K, Srinivasan N, Partridge NC, Selvamurugan N The bacterial infection is one of the major problems associated with implant and reconstructive surgery of bone. Hence, the aim of this study was to develop biomaterials having antibacterial activity for bone tissue engineering. The hydroxyapatite nanoparticles (nHAp) improve the mechanical properties and incorporate nanotopographic features that mimic the nanostructure of natural bone. We report here for the first time the synthesis and characterization of nHAp and nHAp soaked with copper (nHAp-Cu) using SEM, AFM, FTIR and XRD. The antibacterial activity of nHAp and nHAp-Cu was determined using Gram-positive and Gram-negative bacterial strains. To have accelerated antibacterial activity, polyethylene glycol 400 (PEG 400), a synthetic biodegradable polymer was also added along with nHAp-Cu. The nHAp-Cu/PEG 400 had increased antibacterial activity towards Gram-positive than Gram-negative bacterial strains. The cytotoxicity of nHAp-Cu/PEG 400 was determined using MTT assay with rat primary osteoprogenitor cells and these biomaterials were found to be non-toxic. Hence, based on these results we suggest that the biomaterials containing nHAp-Cu/PEG 400 can be used as antibacterial materials in bone implant and bone regenerative medicine. PMID: 21323106 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Cell therapy for critical limb ischemia: moving forward one step at a time. Circ Cardiovasc Interv. 2011 Feb 1;4(1):2-5 Authors: Gupta R, Losordo DW PMID: 21325196 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Chromatin structure of pluripotent stem cells and induced pluripotent stem cells. Brief Funct Genomics. 2011 Jan;10(1):37-49 Authors: Delgado-Olguín P, Recillas-Targa F Pluripotent embryonic stem (ES) cells are specialized cells with a dynamic chromatin structure, which is intimately connected with their pluripotency and physiology. In recent years somatic cells have been reprogrammed to a pluripotent state through over-expression of a defined set of transcription factors. These cells, known as induced pluripotent stem (iPS) cells, recapitulate ES cell properties and can be differentiated to apparently all cell lineages, making iPS cells a suitable replacement for ES cells in future regenerative medicine. Chromatin modifiers play a key function in establishing and maintaining pluripotency, therefore, elucidating the mechanisms controlling chromatin structure in both ES and iPS cells is of utmost importance to understanding their properties and harnessing their therapeutic potential. In this review, we discuss recent studies that provide a genome-wide view of the chromatin structure signature in ES cells and iPS cells and that highlight the central role of histone modifiers and chromatin remodelers in pluripotency maintenance and induction. PMID: 21325400 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue engineering of human bladder. Br Med Bull. 2011 Feb 15; Authors: Atala A There are a number of conditions of the bladder that can lead to loss of function. Many of these require reconstructive procedures. However, current techniques may lead to a number of complications. Replacement of bladder tissues with functionally equivalent ones created in the laboratory could improve the outcome of reconstructive surgery. A review of the literature was conducted using PubMed to identify studies that provide evidence that tissue engineering techniques may be useful in the development of alternatives to current methods of bladder reconstruction. A number of animal studies and several clinical experiences show that it is possible to reconstruct the bladder using tissues and neo-organs produced in the laboratory. Materials that could be used to create functionally equivalent urologic tissues in the laboratory, especially non-autologous cells that have the potential to reject have many technical limitations. Current research suggests that the use of biomaterial-based, bladder-shaped scaffolds seeded with autologous urothelial and smooth muscle cells is currently the best option for bladder tissue engineering. Further research to develop novel biomaterials and cell sources, as well as information gained from developmental biology, signal transduction studies and studies of the wound healing response would be beneficial. PMID: 21324973 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Synthesis and characterization of nanoscale-hydroxyapatite-copper for antimicrobial activity towards bone tissue engineering applications. J Biomed Nanotechnol. 2010 Aug;6(4):333-9 Authors: Sahithi K, Swetha M, Prabaharan M, Moorthi A, Saranya N, Ramasamy K, Srinivasan N, Partridge NC, Selvamurugan N The bacterial infection is one of the major problems associated with implant and reconstructive surgery of bone. Hence, the aim of this study was to develop biomaterials having antibacterial activity for bone tissue engineering. The hydroxyapatite nanoparticles (nHAp) improve the mechanical properties and incorporate nanotopographic features that mimic the nanostructure of natural bone. We report here for the first time the synthesis and characterization of nHAp and nHAp soaked with copper (nHAp-Cu) using SEM, AFM, FTIR and XRD. The antibacterial activity of nHAp and nHAp-Cu was determined using Gram-positive and Gram-negative bacterial strains. To have accelerated antibacterial activity, polyethylene glycol 400 (PEG 400), a synthetic biodegradable polymer was also added along with nHAp-Cu. The nHAp-Cu/PEG 400 had increased antibacterial activity towards Gram-positive than Gram-negative bacterial strains. The cytotoxicity of nHAp-Cu/PEG 400 was determined using MTT assay with rat primary osteoprogenitor cells and these biomaterials were found to be non-toxic. Hence, based on these results we suggest that the biomaterials containing nHAp-Cu/PEG 400 can be used as antibacterial materials in bone implant and bone regenerative medicine. PMID: 21323106 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Stiffness of photocrosslinked RGD-Alginate gels regulates adipose progenitor cell behavior. Biotechnol Bioeng. 2011 Feb 15; Authors: Chandler EM, Berglund CM, Lee JS, Polacheck WJ, Gleghorn JP, Kirby BJ, Fischbach C Adipose progenitor cells (APCs) are widely investigated for soft tissue reconstruction following tumor resection; however, the long-term success of current approaches is still limited. In order to develop clinically relevant therapies, a better understanding of the role of cell-microenvironment interactions in adipose tissue regeneration is essential. In particular, the effect of extracellular matrix (ECM) mechanics on the regenerative capability of APCs remains to be clarified. We have used artificial ECMs based on photocrosslinkable RGD-alginate to investigate the adipogenic and pro-angiogenic potential of 3T3-L1 preadipocytes as a function of matrix stiffness. These hydrogels allowed us to decouple matrix stiffness from changes in adhesion peptide density or extracellular Ca(2+) concentration and provided a physiologically relevant 3-D culture context. Our findings suggest that increased matrix rigidity promotes APC self-renewal and angiogenic capacity, whereas it inhibits adipose differentiation. Collectively, this study advances our understanding of the role of ECM mechanics in adipose tissue formation and vascularization and will aid in the design of efficacious biomaterial scaffolds for adipose tissue engineering applications. Biotechnol. Bioeng. © 2011 Wiley Periodicals, Inc. PMID: 21328324 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The performance of laminin-containing cryogel scaffolds in neural tissue regeneration. Biomaterials. 2011 Feb 13; Authors: Jurga M, Dainiak MB, Sarnowska A, Jablonska A, Tripathi A, Plieva FM, Savina IN, Strojek L, Jungvid H, Kumar A, Lukomska B, Domanska-Janik K, Forraz N, McGuckin CP Currently, there are no effective therapies to restore lost brain neurons, although rapid progress in stem cell biology and biomaterials development provides new tools for regeneration of central nervous system. Here we describe neurogenic properties of bioactive scaffolds generated by cryogelation of dextran or gelatin linked to laminin - the main component of brain extracellular matrix. We showed that such scaffolds promoted differentiation of human cord blood-derived stem cells into artificial neural tissue in vitro. Our experiments revealed that optimal range of scaffolds' pore size for neural tissue engineering was 80-100 microns. We found that scaffold seeded with undifferentiated, but not neutrally committed stem cells, gave optimal cell adhesion and proliferation in "niche"-like structures. Subsequent differentiation resulted in generation of mature 3D networks of neurons (MAP2+) and glia (S100beta+) cells. We showed that cryogel scaffolds could be transplanted into the brain tissue or organotypic hippocampal slices in a rat models. The scaffolds did not induced inflammation mediated by microglial cells (ED1-, Ox43-, Iba1-) and prevented formation of glial scar (GFAP-). Contrary, laminin-rich scaffolds attracted infiltration of host's neuroblasts (NF200+, Nestin+) indicating high neuroregeneration properties. PMID: 21324403 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Glutathione peroxidase activity in the blood cells of psoriatic patients correlates with their responsiveness to Efalizumab. Free Radic Res. 2011 Feb 16; Authors: Pastore S, Mariani V, Lulli D, Gubinelli E, Raskovic D, Mariani S, Stancato A, de Luca C, Pecorelli A, Valacchi G, Potapovich AI, Kostyuk VA, Korkina LG Abstract Biological treatment of psoriasis, a chronic inflammatory immune-mediated pathology of huge social impact, has become a recent revolutionizing breakthrough in the management of the disease. Apart from anti-TNF-alpha biologics, recombinant proteins-inhibitors of the T lymphocytes-antigen presenting cells interaction, Efalizumab among them, have been successfully used in the therapy of psoriasis. Serious concern regarding safety and efficacy of biologics remains because they induce numerous adverse effects and a significant number of patients are non-responders. Up-to-now, there are no biochemical or/and immunological markers of the clinical efficacy of these drugs. This study searches for immunological and redox markers of the clinical response in the group of psoriatic patients treated with Efalizumab. Clinical response to Efalizumab was assessed by Psoriasis Area and Severity Index and correlated with suppression of T-cell functions, plasma cytokines, membrane-associated polyunsaturated fatty acids (PUFAs), antioxidant enzymes and markers of oxidative stress. A 12-week Efalizumab therapy did not affect abnormal plasma levels of pro-inflammatory cytokines and lower-than-normal content of PUFAs esterified in phospholipids of red cell membranes. It did, however, suppress T-cell-mediated functions and decrease nitrites/nitrates and malonyl dialdehyde levels independently on the clinical outcome. On contrast, activities of glutathione peroxidase (GPx) and glutathione S-transferase in granulocytes were remarkably increased and catalase decreased exclusively in non-responders vs complete or partial responders. High baseline GPx in erythrocytes decreased in responders. It is concluded that clinical response to Efalizumab correlates with GPx activity in the blood cells, suggesting that high hydroperoxide levels are involved in psoriasis persistence. PMID: 21323509 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine: the promises and perils of a Promethean task: Progress in regenerative medicine review series. J Cell Mol Med. 2010 Sep;14(9):2189 Authors: Moldovan NI PMID: 20807284 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue engineering of human bladder. Br Med Bull. 2011 Feb 15; Authors: Atala A There are a number of conditions of the bladder that can lead to loss of function. Many of these require reconstructive procedures. However, current techniques may lead to a number of complications. Replacement of bladder tissues with functionally equivalent ones created in the laboratory could improve the outcome of reconstructive surgery. A review of the literature was conducted using PubMed to identify studies that provide evidence that tissue engineering techniques may be useful in the development of alternatives to current methods of bladder reconstruction. A number of animal studies and several clinical experiences show that it is possible to reconstruct the bladder using tissues and neo-organs produced in the laboratory. Materials that could be used to create functionally equivalent urologic tissues in the laboratory, especially non-autologous cells that have the potential to reject have many technical limitations. Current research suggests that the use of biomaterial-based, bladder-shaped scaffolds seeded with autologous urothelial and smooth muscle cells is currently the best option for bladder tissue engineering. Further research to develop novel biomaterials and cell sources, as well as information gained from developmental biology, signal transduction studies and studies of the wound healing response would be beneficial. PMID: 21324973 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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