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| Geron Go-Ahead Rouses Industry and Researchers
July 30, 2010 at 6:59 PM
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| Geron Corp. said today that it hopes to begin within the next two months a clinical trial for an hESC therapy for spinal injuries, triggering a wave of ebullience from scientists, investors and patient advocates.
The company disclosed its plans following the lifting by the FDA of a hold on the effort.
Clive Cookson of the Financial Times of London caught the global significance. He wrote,
"The | | |
| The National Stem Cell Therapy Patient Registry of Malaysia-Measuring Clinical Outcomes of Stem Cell Therapy.
July 30, 2010 at 12:32 PM
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| | The National Stem Cell Therapy Patient Registry of Malaysia-Measuring Clinical Outcomes of Stem Cell Therapy. Stem Cell Rev. 2010 Jul 29; Authors: Loke SC, Chin SP, Sivanandam S, Goh PP, Ng RK, Saw KY, Lim TO Very few registries worldwide focus on clinical outcomes of stem cell therapy (SCT) as the large number of applications and rapid development of the field complicates registry design considerably. The National Stem Cell Therapy Patient Registry of Malaysia aims to accommodate this by using a main protocol which covers the overall design and administration of the registry, and condition-specific sub-protocols which deal with outcome measures. The registry will start with a few sub-protocols covering existing modes of SCT in Malaysia, with new sub-protocols released periodically as the need arises. PMID: 20669056 [PubMed - as supplied by publisher] | | |
| Cardiac stem cell therapy: progress from the bench to bedside.
July 30, 2010 at 12:32 PM
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| | Cardiac stem cell therapy: progress from the bench to bedside. Heart. 2010 Jul 28; Authors: Lovell MJ, Mathur A In the rush to assess the role of stem cell therapy for cardiovascular disease the details of translation are easily overlooked. This review summarises the progress to date in translating the exciting preclinical results of cardiac repair into man and considers the questions that this area of research has stimulated about the challenges of moving from bench to bedside. PMID: 20668107 [PubMed - as supplied by publisher] | | |
| Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: report of two initial cases.
July 30, 2010 at 8:05 AM
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| | Periurethral injection of autologous adipose-derived stem cells for the treatment of stress urinary incontinence in patients undergoing radical prostatectomy: report of two initial cases. Int J Urol. 2010 Jan;17(1):75-82 Authors: Yamamoto T, Gotoh M, Hattori R, Toriyama K, Kamei Y, Iwaguro H, Matsukawa Y, Funahashi Y OBJECTIVES: To report a novel cell therapy using autologous adipose tissue-derived stem cells (ADSC) for stress urinary incontinence caused by urethral sphincteric deficiency and the outcomes in two initial cases undergoing periurethral injection of stem cells for the treatment of urinary incontinence after radical prostatectomy. METHODS: Two patients with moderate stress incontinence after radical prostatectomy were enrolled. After liposuction of 250 mL of adipose tissue from the abdomen, we isolated ADSC from this tissue by using the Celution system. Subsequently, the isolated ADSC and a mixture of stem cells and adipose tissue were transurethrally injected into the rhabdosphincter and submucosal space of the urethra, respectively. Short-term outcomes during a 12-week follow-up were assessed by a 24-h pad test, a validated patient questionnaire, urethral pressure profile, transrectal ultrasonography, and magnetic resonance imaging. RESULTS: Urinary incontinence progressively improved after 2 weeks of injection up to 12 weeks in terms of decreased leakage volume in a 24-h pad test, decreased frequency and amount of incontinence, and improved quality of life as per the questionnaire. In urethral pressure profile, both maximum urethral closing pressure and functional profile length increased. Ultrasonography and magnetic resonance imaging showed sustained presence of the injected adipose tissue. Enhanced ultrasonography showed a progressive increase in the blood flow to the injected area. No significant adverse events were observed peri- and postoperatively. CONCLUSION: This preliminary study showed that periurethral injection of the autologous ADSC is a safe and feasible treatment modality for stress urinary incontinence. PMID: 20002225 [PubMed - indexed for MEDLINE] | | |
| Feasibility of using sodium chloride as a tracer for the characterization of the distribution of matter in complex multi-compartment 3D bioreactors for stem cell culture.
July 30, 2010 at 7:36 AM
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| | Feasibility of using sodium chloride as a tracer for the characterization of the distribution of matter in complex multi-compartment 3D bioreactors for stem cell culture. Int J Artif Organs. 2010 Jun;33(6):399-404 Authors: Gerlach JC, Witaschek T, Strobel C, Brayfield CA, Bornemann R, Catapano G, Zeilinger K The experimental characterization of the distribution of matter in complex multi-compartment three-dimensional membrane bioreactors for human cell culture is complicated by tracer interactions with the membranes and other bioreactor constituents. This is due to the fact that membranes with a high specific surface area often feature a hydrophobic chemical backbone that may adsorb tracers often used to this purpose, such as proteins and dyes. Membrane selectivity, and its worsening caused by protein adsorption, may also hinder tracer transfer across neighboring compartments, thus preventing effective characterization of the distribution of matter in the whole bioreactor. ?Tracer experiments with sodium chloride (NaCl) may overcome some of these limitations and be effectively used to characterize the distribution of matter in complex 3D multi-compartments membrane bioreactors for stem cell culture. NaCl freely permeates most used membranes, it does not adsorb on uncharged membranes, and its concentration may be accurately measured in terms of solution conductivity. In this preliminary study, the feasibility of complex multi-compartment membrane bioreactors was investigated with a NaCl concentration pulse challenge to characterize how their distribution of matter changes when they are operated under different conditions. In particular, bioreactors consisting of three different membrane types stacked on top of one another to form a 3D network were characterized under different feed conditions. PMID: 20669145 [PubMed - in process] | | |
| A three-dimensional traction/torsion bioreactor system for tissue engineering.
July 30, 2010 at 7:36 AM
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| | A three-dimensional traction/torsion bioreactor system for tissue engineering. Int J Artif Organs. 2010 Jun;33(6):362-9 Authors: Scaglione S, Zerega B, Badano R, Benatti U, Fato M, Quarto R Purpose: The aim of this study was to design, develop and validate a simple, compact bioreactor system for tissue engineering. The resulting bioreactor was designed to achieve ease-of-use and low costs for automated cell-culturing procedures onto three-dimensional scaffolds under controlled torsion/traction regimes. ?Methods: Highly porous poly-caprolactone-based scaffolds were used as substrates colonized by fibroblast cells (3T3 cell line). Constructs were placed within the cylindrical culture chamber, clumped at the ends and exposed to controlled sequences of torsional stimuli (forward/back-forward sequential cycles of 100 degrees from neutral position at a rate of 600 degrees /min) through a stepper-motor; working settings were defined via PC by an easy user-interface. Cell adhesion, morphology, cytoskeletal fiber orientation and gene expression of extracellular matrix proteins (collagen type I, tenascin C, collagen type III) were evaluated after three days of torsional stimulation in the bioreactor system. ?Results and Conclusions: The 3D bioreactor system was validated in terms of sterility, experimental reproducibility and flexibility. Cells adhered well onto the polymeric scaffolds. Collagen type I, tenascin C and collagen type III gene expression were significantly up-regulated when cells were cultured under torsion in the bioreactor for three days. In conclusion, we have developed a simple, efficient and versatile 3D cell-culture system to engineer ligament grafts. This system can be used either as a model to investigate mechanisms of tissue development or as a graft manufacturing system for possible clinical use in the field of regenerative medicine. PMID: 20669141 [PubMed - in process] | | |
| An Adult Myometrial Pluripotential Precursor that Promotes Healing of Damaged Muscular Tissues.
July 30, 2010 at 7:36 AM
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| | An Adult Myometrial Pluripotential Precursor that Promotes Healing of Damaged Muscular Tissues. In Vivo. 2010 Jul-Aug;24(4):431-41 Authors: Gálvez BG, MartÃn NS, Salama-Cohen P, Lazcano JJ, Coronado MJ, Lamelas ML, Alvarez-Barrientes A, Eiró N, Vizoso F, RodrÃguez C The use of adult stem cells for tissue and organ regeneration constitutes a promising alternative therapy in many human diseases that are currently not treatable. We have isolated a new cell type from mouse adult uterine biopsies (murine adult myometrial precursors or mAMPs) by means of using a simple and non-invasive approach. These cells have been characterized by surface markers, being positive for CD31, CD34, CD44, CD117, Stro-1 and Sca-1. A similar cell population (hAMPs) was isolated from human biopsies. AMPs can differentiate in vitro into a number of mesodermal (smooth and skeletal muscle, osteoblasts and adipocytes) as well as epidermal lineages (all neural lineages). AMPs are unusual adult stem cells as they still express some embryonic antigens and remain undifferentiated through a high number of passages before entering senescence. Importantly, when injected into animal models of muscular disease, AMPs can regenerate new muscle fibers, and promote functional muscular recovery. Moreover, these cells can regenerate the uterine lining after wound healing, reconstructing the uterine muscular architecture. In addition, these cells can form new vessels both in vitro and in vivo. We believe that these cells have superior features to other known adult stem cells and, consequently, their use holds great promise for regenerative medicine, drug development and basic research. PMID: 20668309 [PubMed - in process] | | |
| The wnt signaling pathway as a potential target for therapies to enhance bone repair.
July 30, 2010 at 7:36 AM
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| | The wnt signaling pathway as a potential target for therapies to enhance bone repair. Sci Transl Med. 2010 Jul 28;2(42):42ps36 Authors: Einhorn TA The development of new technologies to enhance skeletal healing after fracture or surgery is an important goal of musculoskeletal regenerative medicine. Although the bone morphogenetic proteins have shown some efficacy in this area, there is a need for more effective and less expensive therapies for bone repair and regeneration. A recent report demonstrating that Wnt signaling could be used to stimulate bone healing may provide a new direction for designing anabolic therapies for the skeleton. The identification of human phenotypes demonstrating robust bone formation as a result of mutations in Wnt signaling provides a strong basis for pursuing this area of investigation. PMID: 20668295 [PubMed - in process] | | |
| Cell-Mediated Neuroprotection in a Mouse Model of Human Tauopathy.
July 30, 2010 at 7:36 AM
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| | Cell-Mediated Neuroprotection in a Mouse Model of Human Tauopathy. J Neurosci. 2010 Jul 28;30(30):9973-9983 Authors: Hampton DW, Webber DJ, Bilican B, Goedert M, Spillantini MG, Chandran S Tau protein in a hyperphosphorylated state makes up the intracellular inclusions of several neurodegenerative diseases, including Alzheimer's disease and cases of frontotemporal dementia. Mutations in Tau cause familial forms of frontotemporal dementia, establishing that dysfunction of tau protein is sufficient to cause neurodegeneration and dementia. Transgenic mice expressing human mutant tau in neurons exhibit the essential features of tauopathies, including neurodegeneration and abundant filaments composed of hyperphosphorylated tau. Here we show that a previously described mouse line transgenic for human P301S tau exhibits an age-related, layer-specific loss of superficial cortical neurons, similar to what has been observed in human frontotemporal dementias. We also show that focal neural precursor cell implantation, resulting in glial cell differentiation, leads to the sustained rescue of cortical neurons. Together with evidence indicating that astrocyte transplantation may be neuroprotective, our findings suggest a beneficial role for glial cell-based repair in neurodegenerative diseases. PMID: 20668182 [PubMed - as supplied by publisher] | | |
| Defining Cell Identity by Comprehensive Gene Expression Profiling.
July 30, 2010 at 7:36 AM
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| | Defining Cell Identity by Comprehensive Gene Expression Profiling. Curr Med Chem. 2010 Jul 29; Authors: Toyoda M, Hamatani T, Okada H, Matsumoto K, Saito H, Umezawa A The human body is composed of 60 trillion cells, which have their origin in a fertilized egg. During development, the potential of a cell or tissue can be achieved by environmental manipulation. Then, what molecular determinants underlie or accompany the potential of the cells? To obtain a broader understanding of these problems, it is important to analyze all transcripts / genes in a wide selection of cell types. The development of microarray technologies, which allow us to undertake parallel analyses of many genes, has led to a new era in medical science. In this review, we show that the global expression data have clearly elucidated discernible major trends of the phenomenon in preimplantation development and epithelial-mesenchymal transition, and of the character of marrow stromal cells, which are attracting a great deal of attention as they represent a valuable source of cells for regenerative medicine. One of the interesting results is obtained from microarray data of marrow stromal cells: OP9 cells that have been recognized as a type of niche-constituting preadipocyte derived from marrow stroma, are found to be chondroblasts. We also describe what effect each type of expression data would bring to reproductive and regenerative medicine, as well as offering an excellent model of cell differentiation in biology. PMID: 20666720 [PubMed - as supplied by publisher] | | |
| Micro-Cavitary Hydrogel Mediating Phase Transfer Cell Culture for Cartilage Tissue Engineering.
July 30, 2010 at 7:36 AM
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| | Micro-Cavitary Hydrogel Mediating Phase Transfer Cell Culture for Cartilage Tissue Engineering. Tissue Eng Part A. 2010 Jul 28; Authors: Gong Y, Su K, Lau TT, Zhou R, Wang DA Hydrogels have been widely used as cell-laden vehicles for therapeutic transplantation in regenerative medicine. Although the advantages of biocompatibility and injectability for in situ grafting have made hydrogel a superior candidate in tissue engineering, there remain challenges in long-term efficacy of tissue development using hydrogel, especially when more sophisticated applications are demanded. The major bottleneck lies in environmental constraints for neo-tissue generation in the gel bulk such as proliferation of encapsulated cells (colonies) per se and also accommodation of their endogenously produced extracellular matrices (ECMs). In this study, we endeavor to develop an innovative tissue engineering system to overcome these drawbacks through a novel micro-cavitary hydrogel (MCG)-based scaffolding technology and a novel phase transfer cell culture (PTCC) strategy to enable phenotypically bona fide neo-tissue formation in an injectable artificial graft. For this purpose, microspherical cavities are created in cell-encapsulating hydrogel bulk via a retarded dissolution of co-encapsulated gelatin microspheres. Based on proliferation and affinity selection, the encapsulated cell colonies adjacent to the gel/cavity interface will spontaneously outgrow the hydrogel phase and sprout into cavities, enabling neo-tissue islets to fill up the voids and further expand throughout the whole system for full tissue regeneration. The design of MCG-PTCC strategy was elicited from an observation of a spontaneous dynamic outgrowth of chondrocytes from the edge of a cell-laden hydrogel construct over prolonged cultivation - a phenomenon named "edge flourish" (EF). This MCG-PTCC strategy potentially introduce a new application to hydrogels in the field of regenerative medicine through elevation of its role as a cell vehicle to a 3D-transplantable growth-guiding platform for further development of newly generated tissues that better fulfill the demanding criteria of scaffolds in therapeutic tissue regeneration. Keywords: Biomaterials; Hydrogel; Tissue Engineering; Phase Transfer Cell Culture; Regenerative Medicine. PMID: 20666616 [PubMed - as supplied by publisher] | | |
| Fluid Shear Stress Promotes an Endothelial-like Phenotype during the Early Differentiation of Embryonic Stem Cells.
July 30, 2010 at 7:36 AM
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| | Fluid Shear Stress Promotes an Endothelial-like Phenotype during the Early Differentiation of Embryonic Stem Cells. Tissue Eng Part A. 2010 Jul 28; Authors: Ahsan T, Nerem RM Stem and progenitor cells are emerging as a potential source for cell-based therapies, in which large homogenous populations of differentiated cells are frequently deemed necessary for efficacy. Methods focused on biochemical cues have not yet yielded the numbers of endothelial cells thought necessary for cardiovascular applications. Interest in alternate methods has prompted the study of physical cues on stem and progenitor cell differentiation. In this study, fluid-based shear stress, at levels comparable to those experienced by endothelial cells in large vessels, was applied during the first few days of mouse embryonic stem cell differentiation. After two days of applied shear stress, there were increases in cell proliferation and in protein expression of endothelial markers (FLK1, VECAD, and PECAM). Furthermore, treatment increased the number of FLK1+ cells from 1% to 40%, which were then capable of forming vessel-like structures in vitro. Thus, shear stress may be used to direct differentiation of embryonic stem cells towards an endothelial-like phenotype, helping to address the cell sourcing issue in cardiovascular regenerative medicine and tissue engineering. PMID: 20666609 [PubMed - as supplied by publisher] | | |
| Central role for Dab2 in mesenchymal stem cardiac protein expression and functional consequences after engraftment in acute myocardial infarction.
July 30, 2010 at 7:36 AM
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| | Central role for Dab2 in mesenchymal stem cardiac protein expression and functional consequences after engraftment in acute myocardial infarction. Stem Cells Dev. 2010 Jul 28; Authors: Mayorga ME, Dong F, Sundararaman S, Huang Y, Jiang Y, Howe PH, Penn MS Adult mesenchymal stem cells (MSC) have been shown to spontaneously express cardiac proteins (CP) in vitro and to improve cardiac function after transplantation into experimentally induced acute myocardial infarction (AMI). However, if these effects are the result of MSC cardiac differentiation or a mere cooperative cellular interaction is a matter of active debate. Additionally, the molecular mechanisms involved in CP expression by adult stem cells in vitro and its possible benefit for cardiac regeneration and improved function remains unclear. Here we show that although MSC effectively engraft in AMI tissue, this engraftment leads to down-regulation of CP expression in the implanted MSC. We also found that pre-transplantation cardiac specification of MSC by exposure of the cells to TGFbeta1, led to sustained MSC CP expression without altering engraftment efficiency. This increase in CP expression was associated with greater improvement in cardiac function one and four weeks after AMI with TGFbeta1-pretreated MSC. We discovered that the TGFbeta1-enhanced cardiac potential of MSC was mediated by down-regulation of disabled-2 (Dab2) expression; suggesting an inverse correlation between Dab2 levels and CP expression/cardiac functional improvement following MSC engraftment. Our investigations further demonstrate that loss of Dab2 expression was sufficient to induce MSC CP expression and improve cardiac function following MSC engraftment after AMI. In summary, we define a novel role for the TGFbeta1 receptor adaptor protein Dab2 as a regulator of CP expression in MSC and its potential as a molecular target for the enhancement of stem cell cardiac specification for transplantation therapies. PMID: 20666606 [PubMed - as supplied by publisher] | | |
| Autologous chondrocyte implantation in cartilage lesions of the knee: long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique.
July 30, 2010 at 7:36 AM
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| | Autologous chondrocyte implantation in cartilage lesions of the knee: long-term evaluation with magnetic resonance imaging and delayed gadolinium-enhanced magnetic resonance imaging technique. Am J Sports Med. 2010 May;38(5):943-9 Authors: Vasiliadis HS, Danielson B, Ljungberg M, McKeon B, Lindahl A, Peterson L BACKGROUND: Various treatment options are available for articular cartilage lesions, but controversy exists regarding the quality of the repair tissue and the durability of the results posttreatment. Noninvasive techniques are needed for the assessment of the repair tissue. HYPOTHESIS: Magnetic resonance imaging (MRI) with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) can give valuable information regarding the quality and quantity of the repaired cartilage lesion. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Thirty-six knees in 31 patients were assessed 9 to 18 years after treatment with autologous chondrocyte implantation (ACI). All patients had isolated lesions. The knees were clinically evaluated with the Knee injury and Osteoarthritis Outcome Score and the dGEMRIC technique. The T1 value was measured for 2 regions of interest (ROIs), 1 in the repair tissue area (ROI 1) and 1 in the surrounding cartilage (ROI 2), giving information of the content of proteoglycans. RESULTS: The average T1 value in ROI 1 was 467.5 milliseconds and in ROI 2, 495.3 milliseconds, which yielded no significant difference, thus suggesting comparable levels of proteoglycans in the repair tissue and surrounding cartilage. Intralesional osteophytes were in 64% of the lesions, mainly in younger patients with osteochondritis dissecans lesions or a history of subchondral bone surgeries. Medium or large bone marrow edema was found in 14% of the knees and subchondral cysts, in 39%. There was no correlation between the KOOS and any MRI findings. CONCLUSION: Magnetic resonance imaging with dGEMRIC gives valuable information for the macroscopic appearance and micro-molecular quality of the repair tissue after ACI. Nine to 18 years posttreatment, the quality of the repair tissue is similar to the surrounding normal cartilage, although intralesional osteophytes, subchondral cysts, and bone marrow edema were common. The defect area is restored in most patients. However, there was no correlation between the dGEMRIC values and the KOOS outcomes. PMID: 20185841 [PubMed - indexed for MEDLINE] | | | | 
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