|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | California Lt. Gov. Gavin Newsom plans to nominate Southern California investor Jonathan Thomas for chair of the California stem cell agency, according to the San Francisco Business Times.
Reporter Ron Leuty cited an anonymous source in reporting the move today in his story on the nomination of Thomas by Gov. Jerry Brown and state Treasurer Bill Lockyer. State Controller John Chiang is yet to | | | | | | | | | | | | | | | | | | | | | | | | Here is the text of what Prop. 71 stipulates are the legal criteria for the CIRM chair.
"The chairperson and vice chairperson of ICOC (the CIRM governing board) shall be full or part time employees of the institute and shall meet the following criteria:
(A) Mandatory Chairperson Criteria
(i) Documented history in successful stem cell research advocacy.
(ii) Experience with state and federal | | | | | | | | | | | | | | | | | | | | | | | | California Gov. Jerry Brown and the state's treasurer, Bill Lockyer, today nominated the head of a Southern California bond investment firm, Jonathan Thomas, as a candidate to become the new chairman of the $3 billion California stem cell agency.
Two other state officials, Controller John Chiang and Lt. Gov. Gavin Newsom, have the ability to nominate candidates to succeed Robert Klein at the | | | | | | | | | | | | | | | | | | | | | | | | A third candidate and possibly a fourth has emerged for nomination as the new chairman of the $3 billion California stem cell agency.
Bruce Montgomery
One is Bruce Montgomery, an executive in Washington state with Gilead Sciences, Inc., of Foster City, Ca., reliable sources told the California Stem Cell Report. The other is Stephen Juelsgaard of Woodside, Ca. He is a former executive with | | | | | | | | | | | | | | | | | | | | | | | | | Tissue engineering in abdominal wall surgery. Minerva Chir. 2011 Apr;66(2):129-43 Authors: Bellows C, Smith A, Hodde J, Hiles M Abdominal wall defects and tissue loss that result from traumatic injury, surgical resection, failure of abdominal closures (i.e., incisional hernias) or ventral hernias are a common clinical problem. Currently, the repair of these tissue defects represents a reconstructive challenge to surgeons. The goal of abdominal wall reconstruction is to restore and maintain a functional abdominal wall. This article reviews the current and potential tissue engineering strategies for the repair of abdominal wall defects and suggests some innovative approaches for the translation to the clinical setting. PMID: 21593715 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The influence of elastin-like recombinant polymer on the self-renewing potential of a 3D tissue equivalent derived from human lamina propria fibroblasts and oral epithelial cells. Biomaterials. 2011 May 16; Authors: Kinikoglu B, Rodríguez-Cabello JC, Damour O, Hasirci V Three-dimensional epithelial tissue equivalents tend to lose their self-renewing potential progressively during culture as their epithelial cells lose their proliferative capacity with time. Even though the tissue engineered construct can mimic the native tissue well, it rapidly degrades after implantation due to the insufficient number of proliferating cells in the equivalent. In the present study we demonstrate for the first time that the use of an elastin-like recombinant polymer (ELR) engineered to contain the cell adhesion peptide RGD can result in a 3D tissue equivalent with high self-renewing potential, containing as many proliferative cells as the native tissue itself. The 3D tissue equivalent was reconstructed by the coculture of human lamina propria fibroblasts and oral epithelial cells in the nanofibrous ELR-collagen scaffold. Histological, immunohistological and transmission electron microscopic analyses of this oral mucosa equivalent demonstrated the expression of markers characteristic of epithelial proliferation (Ki67) and differentiation (keratin 13), and also the presence of a pluristratified epithelium and an ultrastructurally well-organized basement membrane expressing laminin 332. The synthesis of new extracellular matrix by the fibroblasts was also demonstrated. The scaffold proposed here presents great potential for tissue engineering applications, and also for studies of epithelial proliferation, and epithelial disorders including carcinogenesis. PMID: 21592566 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Autologous cultured epidermis: industrialization of regenerative medicine. Nippon Yakurigaku Zasshi. 2011 Mar;137(3):150-3 Authors: Inoie M, Ozawa Y PMID: 21415565 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Heart regeneration. Nature. 2011 May 19;473(7347):326-35 Authors: Laflamme MA, Murry CE Heart failure plagues industrialized nations, killing more people than any other disease. It usually results from a deficiency of specialized cardiac muscle cells known as cardiomyocytes, and a robust therapy to regenerate lost myocardium could help millions of patients every year. Heart regeneration is well documented in amphibia and fish and in developing mammals. After birth, however, human heart regeneration becomes limited to very slow cardiomyocyte replacement. Several experimental strategies to remuscularize the injured heart using adult stem cells and pluripotent stem cells, cellular reprogramming and tissue engineering are in progress. Although many challenges remain, these interventions may eventually lead to better approaches to treat or prevent heart failure. PMID: 21593865 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Combined 3D and hypoxic culture improves cartilage-specific gene expression in human chondrocytes. Acta Orthop. 2011 Apr;82(2):234-40 Authors: Foldager CB, Nielsen AB, Munir S, Ulrich-Vinther M, Søballe K, Bünger C, Lind M In vitro expansion of autologous chondrocytes is an essential part of many clinically used cartilage repair treatments. Native chondrocytes reside in a 3-dimensional (3D) network and are exposed to low levels of oxygen. We compared monolayer culture to combined 3D and hypoxic culture using quantitative gene expression analysis. PMID: 21434761 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Regulation of electrospun scaffold stiffness via coaxial core diameter. Acta Biomater. 2011 Mar;7(3):1133-9 Authors: Drexler JW, Powell HM Scaffold mechanics influence cellular behavior, including migration, phenotype and viability. Scaffold stiffness is commonly modulated through cross-linking, polymer density, or bioactive coatings on stiff substrates. These approaches provide useful information about cellular response to substrate stiffness; however, they are not ideal as the processing can change substrate morphology, density or chemistry. Coaxial electrospinning was investigated as a fabrication method to produce scaffolds with tunable stiffness and strength without changing architecture or surface chemistry. Core solution concentration, solvent and feed rate were utilized to control core diameter with higher solution concentration and feed rate positively correlating with increased fiber diameter and stiffness. Coaxial scaffolds electrospun with an 8 wt./vol.% polycaprolactone (PCL)-HFP solution at 1 ml h(-1) formed scaffolds with an average core diameter of 1.1±0.2 μm and stiffness of 0.027±3.3×10(-3) N mm(-1). In contrast, fibers which were 2.6±0.1 μm in core diameter yielded scaffolds with a stiffness of 0.065±4.7×10(-3) N mm(-1). Strength and stiffness positively correlated with core diameter with no significant difference in total fiber diameter and interfiber distance observed in as-spun scaffolds. These data indicate that coaxial core diameter can be utilized to tailor mechanical properties of three-dimensional scaffolds and would provide an ideal scaffold for assessing the effect of scaffold mechanics on cell behavior. PMID: 20977951 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Overview of Tracheal Tissue Engineering: Clinical Need Drives the Laboratory Approach. Ann Biomed Eng. 2011 May 19; Authors: Ott LM, Weatherly RA, Detamore MS Breathing is a natural function that most of us do not even think about, but for those who suffer from disease or damage of the trachea, the obstruction of breathing can mean severe restrictions to quality of life or may even be fatal. Replacement and reconstruction of the trachea is one of the most difficult procedures in otolaryngology/head and neck surgery, and also one of the most vital. Previous reviews have focused primarily on clinical perspectives or instead on engineering strategies. However, the current review endeavors to bridge this gap by evaluating engineering approaches in a practical clinical context. For example, although contemporary approaches often include in vitro bioreactor pre-culture, or sub-cutaneous in vivo conditioning, the limitations they present in terms of regulatory approval, cost, additional surgery, and/or risk of infection challenge engineers to develop the next generation of biodegradable/resorbable biomaterials that can be directly implanted in situ. Essentially, the functionality of the replacement is the most important requirement. It must be the correct shape and size, achieve an airtight fit, resist collapse as it is replaced by new tissue, and be non-immunogenic. As we look to the future, there will be no one-size-fits-all solution. PMID: 21594727 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Revitalization of cortical bone allograft by application of vascularized scaffolds seeded with osteogenic induced adipose tissue derived stem cells in a rabbit model. Arch Orthop Trauma Surg. 2011 May 19; Authors: Kloeters O, Berger I, Ryssel H, Megerle K, Leimer U, Germann G BACKGROUND: Adipogenous tissue derived stem cells (ASC) are available in abundance in the human body and can differentiate in the presence of lineage-specific induction factors, for example, in myogenic, adipogenic, chondrogenic and osteogenic cells. The aim of this study was to evaluate the impact of osteogenic induced ASC's (O-ASC) on revascularization and cellular repopulation of avital cortical bone employing a vascularized bovine scaffold. METHODS: An inguinal arterio-venous bundle was dissected in the groin of female white New Zealand rabbits (n = 6) and placed centrally inside an O-ASC seeded scaffold via a central drill hole. In the same surgical session this construct was placed into a segment of avital cortical bone allograft from a donor rabbit. Unseeded scaffolds that were implanted and treated in the same fashion served as controls (n = 6). In order to prevent external revascularization, all constructs were wrapped in silicon foil and finally implanted in the rabbits' groin. Three months later, the constructs were explanted and investigated for vascularization of (a) the scaffold (b) the surrounding bone allograft. Histological stainings to determine cell growth, cellular repopulation of the scaffold and the cortical bone matrix, as well as inflammatory parameters were carried out. RESULTS: O-ASC seeded scaffolds showed a significant increase in new vessel formation in the scaffold as well as in the bone allograft compared to unseeded scaffolds. Furthermore, new vital osteocytes as a sign of cellular repopulation inside the bone allograft were found only in the treatment group. Vital chondrocytes were only found in the O-ASC seeded scaffolds as well. CONCLUSION: The presence of O-ASC significantly induce neo-vascularization and osteocytic repopulation of previously avital bone allograft as opposed to unseeded scaffolds in a rabbit model. Hence, this model might be of relevant value for future bone tissue engineering research and for re-vitalizing marginally nourished bone such as in avascular bone necrosis. PMID: 21594572 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effects of biomimetic surfaces and oxygen tension on redifferentiation of passaged human fibrochondrocytes in 2D and 3D cultures. Biomaterials. 2011 May 16; Authors: Tan GK, Dinnes DL, Myers PT, Cooper-White JJ Due to its limited healing potential within the inner avascular region, functional repair of the meniscus remains a significant challenge in orthopaedic surgery. Tissue engineering of a meniscus implant using meniscal cells offers the promise of enhancing the reparative process and achieving functional meniscal repair. In this work, using quantitative real-time reverse transcriptase polymerase chain reaction (RT-qPCR) analysis, we show that human fibrochondrocytes rapidly dedifferentiate during monolayer expansion on standard tissue culture flasks, representing a significant limit to clinical use of this cell population for meniscal repair. Previously, we have characterized and described the feasibility of a tailored biomimetic surface (C6S surface) for reversing dedifferentiation of monolayer-expanded rat meniscal cells. The surface is comprised of major meniscal extracellular matrix (ECM) components in the inner region, namely collagen I/II (at a 2:3 ratio) and chondroitin-6-sulfate. We thus have further evaluated the effects of the C6S surface, alongside a number of other tailored surfaces, on cell adhesion, proliferation, matrix synthesis and relevant marker gene expression (collagen I, -II, aggrecan and Sox-9 etc) of passaged human fibrochondrocytes in 2D (coated glass coverslips) and 3D (surface-modified polymeric scaffolds) environments. We show that the C6S surface is permissive for cell adhesion, proliferation and ECM synthesis, as demonstrated using DNA quantification, 1,9-dimethylmethylene blue (DMMB) assay, histology and immunohistochemistry. More importantly, RT-qPCR analyses corroborate the feasibility of the C6S surface for reversing phenotypic changes, especially the downregulation of collagen II, of dedifferentiated human fibrochondrocytes. Furthermore, human fibrochondrocyte redifferentiation was enhanced by hypoxia in the 3D cultures, independent of hypoxia inducible factor (HIF) transcriptional activity and was shown to potentially involve the transcriptional activation of Sox-9. PMID: 21592565 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Copper and homocysteine in cardiovascular diseases. Pharmacol Ther. 2011 Mar;129(3):321-31 Authors: Kang YJ High blood copper (Cu) and homocysteine (Hcy) concentrations have been independently reported as risk factors for cardiovascular diseases. When they are simultaneously measured, a concomitant increase in both parameters in association with vascular dysfunction has been observed. Cu chelator penicillamine can significantly diminish the inhibitory effect of Hcy on endothelial function, which has led to the interpretation that Cu mediates the deleterious effect of Hcy. However, Cu itself has been shown to be beneficial to the cardiovascular system. In particular, Cu promotion of angiogenesis has been well documented. Cu stimulates endothelial cell proliferation and differentiation and promotes microtubule formation in cultured saphenous veins. High levels of Hcy do not affect the process of microtubule formation, but the combination of Cu and Hcy leads to a significant inhibitory effect. Under other conditions, Cu does not affect, but Hcy inhibits, the endothelium-dependent relaxation of blood vessels and the combination of both augments the inhibition. Why does Cu produce adverse effects when it co-exists with Hcy? Cu forms complexes with Hcy and the Cu-Hcy complexes possess a deleterious potential due to their redox properties. Cu chelation can remove Cu from the Cu-Hcy complexes, but leaves behind high levels of Hcy and produces Cu deficiency. An alternative approach should focus on the reduction of Hcy, but maintenance of Cu, making detrimental Cu beneficial. A comprehensive understanding of Cu speciation and a development of selective modulation of Cu coordination to Cu-binding molecules to avoid Cu-Hcy complex formation would effectively improve the condition of cardiovascular disease. PMID: 21130114 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Tissue regeneration is a key tool for burn tissue repair]. Zhonghua Shao Shang Za Zhi. 2011 Feb;27(1):6-7 Authors: Huang YS Regenerative medicine is presently one of the hottest areas in medical research. Regenerative medicine is to search for effective biotherapeutic strategies to promote self-repair and regeneration, or to construct new tissues and organs hopefully to improve or restore the function of the injured tissues and organs. Regenerative repair, including constructural and functional repair, may be classified into exogenous and endogenous regenerative repair when considering its cellular or molecular origin. To strengthen researches on regenerative medicine may precipitate the application of new clinical therapeutic strategies, and supply effective therapeutic means for treatment of severe burns. PMID: 21591332 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Heart regeneration. Nature. 2011 May 19;473(7347):326-35 Authors: Laflamme MA, Murry CE Heart failure plagues industrialized nations, killing more people than any other disease. It usually results from a deficiency of specialized cardiac muscle cells known as cardiomyocytes, and a robust therapy to regenerate lost myocardium could help millions of patients every year. Heart regeneration is well documented in amphibia and fish and in developing mammals. After birth, however, human heart regeneration becomes limited to very slow cardiomyocyte replacement. Several experimental strategies to remuscularize the injured heart using adult stem cells and pluripotent stem cells, cellular reprogramming and tissue engineering are in progress. Although many challenges remain, these interventions may eventually lead to better approaches to treat or prevent heart failure. PMID: 21593865 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Blocking MAPK Signaling Downregulates CCL21 in Lymphatic Endothelial Cells and Impairs Contact Hypersensitivity Responses. J Invest Dermatol. 2011 May 19; Authors: Miyagaki T, Sugaya M, Okochi H, Asano Y, Tada Y, Kadono T, Blauvelt A, Tamaki K, Sato S CCL21 expression by lymphatic endothelial cells (LECs) is essential for migration of CCR7+ immune cells from skin to regional lymph nodes (LNs). We investigated the importance of mitogen-activated protein kinase (MAPK) signaling in CCL21 expression by ECs in vitro and in vivo. Normal human dermal lymphatic microvascular ECs (HMVEC-dLy) stimulated in vitro with oncostatin M (OSM) expressed high amounts of CCL21 mRNA. CCL21 protein expression by HMVEC-dLy was also markedly increased by OSM compared with unstimulated cultures. Marked phosphorylation of MAPK 44/42 was detected in HMVEC-dLy stimulated by OSM. CCL21 expression by HMVEC-dLy was blocked by a JAK inhibitor 1, JAK3 inhibitor, and U0126 (a MAPK kinase inhibitor) in vitro, all of which blocked phosphorylation of MAPK 44/42. In addition, injection of U0126 into murine skin significantly decreased CCL21 mRNA and protein expression. Moreover, injection of U0126 before sensitization decreased migration of dendritic cells to draining LNs and decreased contact hypersensitivity responses. In summary, these results suggest that the MAPK pathway is important for CCL21 expression by LECs in vitro and in vivo. Blocking MAPK signaling within skin may offer a novel approach to treatment of inflammatory skin diseases.Journal of Investigative Dermatology advance online publication, 19 May 2011; doi:10.1038/jid.2011.135. PMID: 21593766 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | ZPK/DLK, a Mitogen-Activated Protein Kinase Kinase Kinase, Is a Critical Mediator of Programmed Cell Death of Motoneurons. J Neurosci. 2011 May 18;31(20):7223-8 Authors: Itoh A, Horiuchi M, Wakayama K, Xu J, Bannerman P, Pleasure D, Itoh T Activation of mitogen-activated protein kinase pathways is critically involved in naturally occurring programmed cell death of motoneurons during development, but the upstream mediators remain undetermined. We found that mice deficient in ZPK, also called DLK (ZPK/DLK), an upstream kinase in these pathways, have twice as many spinal motoneurons as do their wild-type littermates. Nuclear HB9/MNX1-positive motoneuron pools were generated similarly in the spinal cord of both ZPK/DLK-deficient and wild-type embryos. Thereafter, however, significantly less apoptotic motoneurons were found in ZPK/DLK-deficient embryos compared with wild-type embryos, resulting in retention of excess numbers of motoneurons after birth. Notably, these excess motoneurons remained viable without atrophic changes in the ZPK/DLK-deficient mice surviving into adulthood. Analysis of the diaphragm and the phrenic nerve revealed that clustering and innervation of neuromuscular junctions were indistinguishable between ZPK/DLK-deficient and wild-type mice, whereas the proximal portion of the phrenic nerve of ZPK/DLK-deficient mice contained significantly more axons than the distal portion. This result supports the hypothesis that some excess ZPK/DLK-deficient motoneurons survived without atrophy despite failure to establish axonal contact with their targets. This study provides compelling evidence for a critical role for ZPK/DLK in naturally occurring programmed cell death of motoneurons and suggests that ZPK/DLK could become a strategic therapeutic target in motor neuron diseases in which aberrant activation of the apoptogenic cascade is involved. PMID: 21593306 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Rescue of ATP7B function in hepatocyte-like cells from Wilson's disease induced pluripotent stem cells using gene therapy or the chaperone drug curcumin. Hum Mol Genet. 2011 May 18; Authors: Zhang S, Chen S, Li W, Guo X, Zhao P, Xu J, Chen Y, Pan Q, Liu X, Zychlinski D, Lu H, Tortorella MD, Schambach A, Wang Y, Pei D, Esteban MA Directed hepatocyte differentiation from human induced pluripotent stem cells (iPSCs) potentially provides a unique platform for modeling liver genetic diseases and performing drug toxicity screening in vitro. Wilson's disease is a genetic disease caused by mutations in the ATP7B gene, whose product is a liver transporter protein responsible for coordinated copper export into bile and blood. Interestingly, the spectrum of ATP7B mutations is vast and can influence clinical presentation (a variable spectrum of hepatic and neural manifestations), though the reason is not well understood. Here we describe the generation of iPSCs from a Chinese patient with Wilson's disease that bears the R778L Chinese hotspot mutation in the ATP7B gene. These iPSCs were pluripotent and could be readily differentiated into hepatocyte-like cells that displayed abnormal cytoplasmic localization of mutated ATP7B and defective copper transport. Moreover, gene correction using a self-inactivating lentiviral vector that expresses codon optimized-ATP7B or treatment with the chaperone drug curcumin could reverse the functional defect in vitro. Hence, our work describes an attractive model for studying the pathogenesis of Wilson's disease that is valuable for screening compounds or gene therapy approaches aimed to correct the abnormality. In the future, once relevant safety concerns (including the stability of the mature liver-like phenotype) and technical issues for the transplantation procedure are solved, hepatocyte-like cells from similarly genetically corrected iPSCs could be an option for autologous transplantation in Wilson's disease. PMID: 21593220 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Filling the evidence gap: how can we improve the outcome of neonatal encephalopathy in the next 10 years? Brain Dev. 2011 Mar;33(3):221-8 Authors: Iwata O, Iwata S Neonatal encephalopathy associated with perinatal hypoxia-ischaemia is one of the most common causes of death and permanent disability worldwide. However, of a wide range of "experimentally neuroprotective treatments" invented so far, only therapeutic hypothermia has been promoted into a standard clinical practice. Such a wide gap in the efficacy of neuroprotective treatments between the experimental setting and clinical practice may be attributed to the strategic flaw in translating basic knowledge into clinical care. When previous clinical studies are carefully reviewed, one may notice that few therapeutic options were chosen based on their track records in experimental studies; protective effects of some drugs had been assumed only based on their pharmacokinetics in adult species; several therapies were chosen merely because clinicians were familiar to these treatments for other purpose; some other therapies were imported too preliminarily from laboratory to clinical practice, potentially ignoring the difference in physiological and pathological backgrounds between rodent models and human patients. When further clinical trials are planned, it is important to ask whether (i) the treatment is supported by pharmacokinetics specific to immature brain, and (ii) the neuroprotective effect of the treatment has consistently been demonstrated using clinically relevant models and study designs. The use of translational large animal models allows the practical simulation and fine-tuning of clinical protocols, which may further assist successful translation of basic knowledge. In addition to the effort to develop alternative therapeutic options, it is important to maximise the effect of the current only neuroprotective option, or therapeutic hypothermia. Independent variables which influence the efficacy of hypothermia have to be elucidated to improve its therapeutic protocol, and to increase the number of patients who will benefit from this treatment. PMID: 21185138 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | [Ponderance over tissue regeneration and regenerative medicine]. Zhonghua Shao Shang Za Zhi. 2011 Feb;27(1):1-2 Authors: Fu XB Research in the field of tissue regeneration is a new focus in life science and medicine in the 21st century, hereby I express my personal expectations of its research and translational application in the future. PMID: 21591330 [PubMed - in process] | | | | | | | | | |  | |  | |  |
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