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| Development of bladder dysfunction in a rat model of dopaminergic brain lesion.
July 1, 2010 at 10:36 AM
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| | Development of bladder dysfunction in a rat model of dopaminergic brain lesion. Neurourol Urodyn. 2010 Jun 29; Authors: Soler R, Füllhase C, Santos C, Andersson KE AIMS: Parkinson's disease (PD) is one of the most common neurological disorders causing lower urinary tract dysfunction. We evaluated the temporal development of bladder dysfunction in rat PD model where urodynamic changes were induced by unilateral injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB). METHODS: Female Sprague-Dawley rats underwent a unilateral stereotaxic injection of 6-OHDA or vehicle (sham group) into the MFB. Cystometry was performed in conscious animals at 3, 14, and 28 days after the injury. Aged-matched unlesioned rats were used as healthy controls. RESULTS: Three days after lesion 6-OHDA rats showed higher threshold (TP), maximum pressures (MP), and spontaneous activity (SA) compared to healthy controls. Sham animals exhibited higher TP. After 14 days 6-OHDA rats had also higher micturition frequency, decreased bladder capacity, micturition volume and bladder compliance (Bcom) compared to sham and healthy controls. Sham animals showed lower Bcom and higher MP and SA. After 28 days, 6-OHDA rats exhibited the same changes as those in 14 days, while sham-operated animals showed parameters similar to those in healthy controls. CONCLUSIONS: These findings suggest that 6-OHDA lesion of the MFB causes bladder dysfunction already after 3 days. A pattern of detrusor overactivity was more clearly defined 14 days after the injection and persisted for 28 days. Cystometry may be a useful tool to study the pathophysiology of bladder dysfunction in PD, and urodynamic parameters may possibly be used to evaluate the effects of therapeutic interventions. Neurourol. Urodyn. (c) 2010 Wiley-Liss, Inc. PMID: 20589898 [PubMed - as supplied by publisher] | | |
| Design of cellular porous biomaterials for wall shear stress criterion.
July 1, 2010 at 10:36 AM
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| | Design of cellular porous biomaterials for wall shear stress criterion. Biotechnol Bioeng. 2010 Jun 29; Authors: Chen Y, Zhou S, Cadman J, Li Q The micro-fluidic environment provided by implanted prostheses has a decisive influence on the viability, proliferation and differentiation of cells. In bone tissue engineering, for instance, experiments have confirmed that a certain level of wall shear stress (WSS) is more advantageous to osteoblastic differentiation. This paper proposes a level-set based topology optimization method to regulate fluidic WSS distribution for design of cellular biomaterials. The topological boundary of fluid phase is represented by a level-set model embedded in a higher dimensional scalar function. WSS is determined by the computational fluid dynamics (CFD) analysis in the scale of cellular base-cells. To achieve a uniform WSS distribution at the solid-fluid interface, the difference between local and target WSS is taken as the design criterion, which determines the speed of the boundary evolution in the level-set model. The examples demonstrate the effectiveness of the presented method and exhibit a considerable potential in the design optimization and fabrication of new prosthetic cellular materials for bioengineering applications. Biotechnol. Bioeng. (c) 2010 Wiley Periodicals, Inc. PMID: 20589850 [PubMed - as supplied by publisher] | | |
| Three-dimensional culture systems for the expansion of pluripotent embryonic stem cells Revised- R2.
July 1, 2010 at 10:36 AM
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| | Three-dimensional culture systems for the expansion of pluripotent embryonic stem cells Revised- R2. Biotechnol Bioeng. 2010 Jun 29; Authors: Storm MP, Orchard CB, Bone HK, Chaudhuri JB, Welham MJ Mouse embryonic stem cell (ESC) lines, and more recently human ESC lines, have become valuable tools for studying early mammalian development. Increasing interest in ESCs and their differentiated progeny in drug discovery and as potential therapeutic agents has highlighted the fact that current two-dimensional (2D) static culturing techniques are inadequate for large-scale production. The culture of mammalian cells in three-dimensional (3D) agitated systems has been shown to overcome many of the restrictions of 2D and is therefore likely to be effective for ESC proliferation. Using murine ESCs as our initial model, we investigated the effectiveness of different 3D culture environments for the expansion of pluripotent ESCs. Solohill Collagen, Solohill FACT and Cultispher-S microcarriers were employed and used in conjunction with stirred bioreactors. Initial seeding parameters, including cell number and agitation conditions, were found to be critical in promoting attachment to microcarriers and minimising the size of aggregates formed. While all microcarriers supported the growth of undifferentiated mESCs, Cultispher-S out-performed the Solohill microcarriers. When cultured for successive passages on Cultispher-S microcarriers, mESCs maintained their pluripotency, demonstrated by self-renewal, expression of pluripotency markers and the ability to undergo multi-lineage differentiation. When these optimised conditions were applied to unweaned human ESCs, Cultispher-S microcarriers supported the growth of hESCs that retained expression of pluripotency markers including SSEA4, Tra-1-60, NANOG and OCT-4. Our study highlights the importance of optimisation of initial seeding parameters and provides proof-of-concept data demonstrating the utility of microcarriers and bioreactors for the expansion of hESCs. Biotechnol. Bioeng. (c) 2010 Wiley Periodicals, Inc. PMID: 20589846 [PubMed - as supplied by publisher] | | |
| Continuous scalable blood filtration device using inertial microfluidics.
July 1, 2010 at 10:36 AM
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| | Continuous scalable blood filtration device using inertial microfluidics. Biotechnol Bioeng. 2010 Jun 29; Authors: Mach AJ, Carlo DD Cell separation is broadly useful for applications in clinical diagnostics, biological research, and potentially regenerative medicine. Recent attention has been paid to label-free size-based techniques that may avoid the costs or clogging issues associated with centrifugation and mechanical filtration. We present for the first time a massively parallel microfluidic device that passively separates pathogenic bacteria cells from diluted blood with macroscale performance. The device was designed to process large sample volumes in a high-throughput, continuous manner using 40 single microchannels placed in a radial array with one inlet and two rings of outlets. Each single channel consists of a short focusing, gradual expansion and collection region and uses unique differential transit times due to size-dependent inertial lift forces as a method of cell separation. The gradual channel expansion region is shown to manipulate cell equilibrium positions close to the microchannel walls, critical for higher efficiency collection. We demonstrate >80% removal of pathogenic bacteria from blood after two passes of the single channel system. The massively parallel device can process 240 mL/hr with a throughput of 400 million cells/min. We expect that this parallelizable, robust, and label-free approach would be useful for filtration of blood as well as for other cell separation and concentration applications from large volume samples. Biotechnol. Bioeng. (c) 2010 Wiley Periodicals, Inc. PMID: 20589838 [PubMed - as supplied by publisher] | | |
| Regenerative medicine for insulin deficiency: creation of pancreatic islets and bioartificial pancreas.
July 1, 2010 at 10:36 AM
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| | Regenerative medicine for insulin deficiency: creation of pancreatic islets and bioartificial pancreas. J Hepatobiliary Pancreat Sci. 2010 Jun 30; Authors: Sumi S Recent advances in pancreas organogenesis have greatly improved the understanding of cell lineage from inner cell mass to fully differentiated beta-cells. Based upon such knowledge, insulin-producing cells similar to beta-cells to a certain extent have been generated from various cell sources including embryonic stem cells (ESCs) and induced pluripotent stem (iPS) cells, although fully differentiated cells comparable to beta-cells are not yet available. The bioartificial pancreas is a therapeutic approach to enable allo- and xenotransplantation of islets without immune suppression. Among several types of bioartificial pancreases (BAPs), micro-encapsulated porcine islets are already in use in clinical trials and may, perhaps, replace islet transplantation in the near future. Some types of bioartificial pancreas such as macro-encapsulation are also useful for keeping transplanted cells enclosed in case retrieval is necessary. Therefore, early clinical applications of artificially generated beta-like cells, especially those from ESCs or iPS cells, will be considered in combination with retrievable BAPs. PMID: 20589399 [PubMed - as supplied by publisher] | | |
| Bone marrow derived stem cells in regenerative medicine as Advanced Therapy Medicinal Products.
July 1, 2010 at 10:36 AM
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| | Bone marrow derived stem cells in regenerative medicine as Advanced Therapy Medicinal Products. Am J Transl Res. 2010;2(3):285-95 Authors: Astori G, Soncin S, Cicero VL, Siclari F, Sürder D, Turchetto L, Soldati G, Moccetti T Bone marrow derived stem cells administered after minimal manipulation represent an important cell source for cellbased therapies. Clinical trial results, have revealed both safety and efficacy of the cell reinfusion procedure in many cardiovascular diseases. Many of these early clinical trials were performed in a period before the entry into force of the US and European regulation on cellbased therapies. As a result, conflicting data have been generated on the effectiveness of those therapies in certain conditions as acute myocardial infarction. As more academic medical centers and private companies move toward exploiting the full potential of cellbased medicinal products, needs arise for the development of the infrastructure necessary to support these investigations. This review describes the regulatory environment surrounding the production of cell based medicinal products and give practical aspects for cell isolation, characterization, production following Good Manufacturing Practice, focusing on the activities associated with the investigational new drug development. PMID: 20589167 [PubMed - in process] | | |
| Urinary Bladder Tissue Engineering Using Natural Scaffolds in a Porcine Model: Role of Toll-Like Receptors and Impact of Biomimetic Molecules.
July 1, 2010 at 10:36 AM
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| | Urinary Bladder Tissue Engineering Using Natural Scaffolds in a Porcine Model: Role of Toll-Like Receptors and Impact of Biomimetic Molecules. Cells Tissues Organs. 2010 Jun 30; Authors: Evren S, Loai Y, Antoon R, Islam S, Yeger H, Moore K, Wong K, Gorczynski R, Farhat WA Introduction: Natural scaffolds have been shown to induce T helper 2 (TH2)-specific immune responses in host tissues; however, the precise mechanisms that underlie this immune response are unknown. Using a porcine animal model, we evaluated the role of Toll-like receptors (TLRs) and matrix remodelling in the implantation of bladder acellular matrix (ACM) grafts and ACMs fortified with biomimetic materials. Materials and Methods: Bladders were decellularized with detergent and treated in 3 different ways prior to implantation: ACM alone, hyaluronic acid (HA)-ACM and HA-vascular endothelial growth factor (VEGF)-ACM. Animals were sacrificed at 4 or 10 weeks post-implantation and total gene expressions for TH2 (IL-4), TH1 (IFN-gamma), TLR2, TLR4, and TGF-beta1 were analyzed using real-time RT-PCR. Using histology (H&E and Masson's trichrome) and immunohistochemistry (uroplakin, alpha-smooth muscle actin, CD31 and factor VIII) the regenerative capacity was correlated with the gene expression of different proteins. Results: IL-4, TLR2, and TLR4 gene expression were markedly decreased at 4 and 10 weeks in both the HA-ACM group and the HA-VEGF-ACM group compared to ACM alone. IFN-gamma expression was negligible in all groups and time periods. TGF-beta1 expression was highest in the HA- and VEGF-treated grafts. Recellularization was inversely proportional to TLR and TH2 expression but proportional to TGF-beta1. Conclusion: ACM alone grafts demonstrated stronger TLR4 expression which may promote a distinct TH2 immune response and a reduced regenerative capacity in grafts. Treatment of grafts with HA and VEGF may help regulate host immune responses by reducing TLR4 and IL-4 and increasing TGF-beta1. PMID: 20588005 [PubMed - as supplied by publisher] | | |
| The current role of tissue engineering in head and neck reconstruction.
July 1, 2010 at 10:36 AM
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| | The current role of tissue engineering in head and neck reconstruction. Indian J Cancer. 2010 Jul-Sep;47(3):274-9 Authors: Jallali N, James S, Elmiyeh B, Searle A, Ghattaura A, Dwivedi RC, Kazi R, Harris P Tissue engineering is an emerging field that has the potential to revolutionize the field of reconstructive surgery by providing off-the-shelf replacement products. The literature has become replete with tissue engineering studies, and the aim of this article is to review the contemporary application of tissue-engineered products. The use of tissue-engineered cartilage, bone and nerve in head and neck reconstruction is discussed. PMID: 20587902 [PubMed - in process] | | |
| Inconsistent formation and non function of insulin positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.
July 1, 2010 at 10:36 AM
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| | Inconsistent formation and non function of insulin positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats. Am J Physiol Endocrinol Metab. 2010 Jun 29; Authors: Matveyenko AV, Georgia S, Bhushan A, Butler PC Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore beta-cell mass and function in T1DM. Recently group from Novocell reported successful development of glucose-responsive islet like structures after implantation of pancreatic endoderm derived from human embryonic stem cells (hESC) into immune deficient mice. Our objective was to determine whether implantation of hESC derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with pancreatic endoderm (PE) derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 weeks. Blood glucose, weight and human insulin/c-peptide secretion were monitored by weekly blood draws. Graft beta-cell function was assessed by glucose tolerance test and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 weeks post-implantation, epididymal fat-implanted pancreatic endoderm progressed to develop islet like structures in 50% of implants with a mean beta-cell fractional area of 0.8+/-0.3%. Human c-peptide and insulin was detectable, but at very low levels (c-peptide=50+/-26 pmol/l and insulin=15+/-7 pmol/l), however there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human pancreatic endoderm was implanted in the TheraCyte encapsulation devices. These data confirms that islet like structures do develop from hESC differentiated to pancreatic endoderm by the protocol developed by NovoCell. However the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant. PMID: 20587750 [PubMed - as supplied by publisher] | | |
| Transduction of Cell-Penetrating Peptides into Induced Pluripotent Stem Cells.
July 1, 2010 at 10:36 AM
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| | Transduction of Cell-Penetrating Peptides into Induced Pluripotent Stem Cells. Cell Transplant. 2010 Jun 29; Authors: Yukawa H, Noguchi H, Nakase I, Miyamoto Y, Oishi K, Hamajima N, Futaki S, Hayashi S Induced pluripotent stem (iPS) cells have recently been initially generated by Yamanaka's Group, and then followed by others. iPS cells are expected to have clinical applications including an important role in regenerative medicine. This study focused on the cell-penetrating peptides (CPPs) for differentiation or functional application of iPS cells, because several transduction domains can deliver a large size-independent variety of molecules into cells. Two CPPs, Texas Red-R8 and Rhodamine-TAT, were generated as representative CPPs and these CPPs were tested to determine their ability to penetrate the membrane of iPS cells. Both CPPs were transduced in iPS cells through macropinocytosis classified in endocytosis within 2 hours in a manner consistent with many other cells, and no cytotoxicity and influence on their undifferentiated state was observed. In conclusion, CPPs can be utilized for their differentiation or functional application in iPS cells. PMID: 20587149 [PubMed - as supplied by publisher] | | |
| Evaluation of 28 human embryonic stem cell lines for use as unrelated donors in stem cell therapy: implications of HLA and ABO genotypes.
July 1, 2010 at 10:36 AM
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| | Evaluation of 28 human embryonic stem cell lines for use as unrelated donors in stem cell therapy: implications of HLA and ABO genotypes. Cell Transplant. 2010 Jun 29; Authors: Lee JE, Kang MS, Park MH, Shim SH, Yoon TK, Chung HM, Lee DR For human embryonic stem cells (hESCs) to be used clinically, it is imperative that immune responses evoked by hESCs and their derivates after transplantation should be prevented. Human leukocyte antigens (HLA) and ABO blood group antigens are important histocompatibility factors in graft rejection. HLA matching between recipient and unrelated donors, in particular, is important in improving outcomes in hematopoietic cell transplantation (HCT). We have established and successfully maintained 29 hESC lines and analyzed the HLA and ABO genotypes of these lines. HLA-A, -B, C- and -DR (DRB1) genotyping was performed by polymerase chain reaction (PCR)-sequence based typing and ABO genotyping was carried out by PCR-restriction fragment length polymorphism methods. To determine what proportion of the Korean population would be covered by these cell lines in organ transplantation, 27 cell lines with HLA-A, -B, and -DR data were evaluated for HCT (cord blood) donors and 28 cell lines with HLA-DR and ABO data were evaluated for solid organ (kidney) transplantation donors, and then compared the data with those from 6740 donated cord bloods. When 2 HLA mismatches are allowed for HCT, as currently accepted for cord blood transplantation, it was estimated that about 16% and 25% of the possible recipients can find one or more donor cell lines with </=2 mismatches at A, B, DRB1 allele level and at A, B antigen/DRB1 allele level, respectively. When HLA-DR antigen level matching and ABO compatibility was considered for solid organ (kidney) transplantation, it was estimated that about 29% and 96% of the possible recipients can find one or more ABO compatible donor cell lines with 0 and 1 DR mismatches, respectively. We provided the first report on the HLA and ABO genotypes of hESC lines, and estimated the degree of HLA and ABO matching in organ transplantation for the Korean population. PMID: 20587141 [PubMed - as supplied by publisher] | | |
| Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells.
July 1, 2010 at 10:36 AM
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| | Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells. Stem Cell Res Ther. 2010 Jun 29;1(2):19 Authors: Gimble JM, Guilak F, Bunnell BA ABSTRACT: Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models. This body of work has provided evidence supporting clinical translational applications of adipose-derived cells in safety and efficacy trials. The present article reviews the case reports and phase I-III clinical evidence using autologous adipose-derived cells that have been published, to date, in the fields of gastroenterology, neurology, orthopedics, reconstructive surgery, and related clinical disciplines. Future directions and challenges facing the field are discussed and evaluated. PMID: 20587076 [PubMed - as supplied by publisher] | | |
| Cancerous stem cells: deviant stem cells with cancer-causing misbehavior.
July 1, 2010 at 10:36 AM
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| | Cancerous stem cells: deviant stem cells with cancer-causing misbehavior. Stem Cell Res Ther. 2010;1(2):13 Authors: Chandler JM, Lagasse E ABSTRACT : Stem cells maintain homeostasis in adult tissues via self-renewal and generation of terminally differentiated cells. Alterations in this intricate balance can result in disease. It has become increasingly evident that cancer can be initiated at the level of stem cells. Therefore, understanding what causes stem cells to become cancerous may lead to new therapeutic approaches. Multiple signaling pathways ultimately affect stem cell survival and proliferation, thus maintaining homeostasis in the gut. Changes in these pathways could perturb normal stem cell behavior, leading to cancerous stem cells. In addition, cancerous stem cells show resistance to current therapies and may lead to a dangerous selection process resulting in recurrence and metastasis. Genomic instability, the driving force of mutation and resistance, may give cancerous stem cells an adaptive advantage, especially when subjected to cancer therapies. Targeting the unique characteristics of cancerous stem cells to promote either terminal differentiation or destruction would effectively eradicate cancer and improve patient care and survival. PMID: 20587011 [PubMed - in process] | | |
| Engineered heart tissue graft derived from somatic-cell-nuclear-transferred embryonic stem cells improve myocardial performance in infarcted rat heart.
July 1, 2010 at 10:36 AM
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| | Engineered heart tissue graft derived from somatic-cell-nuclear-transferred embryonic stem cells improve myocardial performance in infarcted rat heart. J Cell Mol Med. 2010 Jun 25; Authors: Lü S, Li Y, Liu S, Wang H, He W, Zhou J, Liu Z, Zhang Y, Lin Q, Duan C, Yang X, Gao S, Wang C Abstract The concept of regenerating diseased myocardium by implanting engineered heart tissue (EHT) is intriguing. Yet it was limited by immune rejection and difficulties to be generated at a size with contractile properties. Somatic cell nuclear transfer (SCNT) is proposed as a practical strategy for generating autologous histocompatible stem (NT-ES) cells to treat diseases. Nevertheless, it is controversial as NT-ES cells may pose risks in their therapeutic application. EHT from NT-ES cells derived cardiomyocytes was generated through a series of improved techniques in a self-made mold to keep the EHTs from contraction and provide static stretch simultaneously. After 7 days of static and mechanical stretching respectively, the EHTs were implanted to the infarcted rat heart. Four weeks after transplantation, the suitability of EHT in heart muscle repair after myocardial infarction was evaluated by histological examination, echocardiography, and multielectrode array (MEA) measurement. The results showed that large (thickness/diameter, 2-4 mm/10 mm) spontaneously contracting EHTs was generated successfully. The EHTs, which were derived from NT-ES cells, integrated and electrically coupled to host myocardium and exerted beneficial effects on the left ventricular function of infarcted rat heart. No teratoma formation was observed in the rat heart implanted with EHTs for 4 weeks. NT-ES cells can be used as a source of seeding cells for cardiac tissue engineering. Large contractile EHT grafts can be constructed in vitro with the ability to survive after implantation and improve myocardial performance of infarcted rat hearts. PMID: 20586830 [PubMed - as supplied by publisher] | | |
| Generation of easily accessible human kidney tubules on two-dimensional surfaces in vitro.
July 1, 2010 at 10:36 AM
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| | Generation of easily accessible human kidney tubules on two-dimensional surfaces in vitro. J Cell Mol Med. 2010 Jun 25; Authors: Zhang H, Lau SF, Heng BF, Teo PY, Alahakoon PK, Ni M, Tasnim F, Ying JY, Zink D Abstract The generation of tissue-like structures in vitro is of major interest for various fields of research including in vitro toxicology, regenerative therapies and tissue engineering. Usually three-dimensional (3D) matrices are used to engineer tissue-like structures in vitro, and for the generation of kidney tubules, 3D gels are employed. Kidney tubules embedded within 3D gels are difficult to access for manipulations and imaging. Here we show how large and functional human kidney tubules can be generated in vitro on two-dimensional (2D) surfaces, without the use of 3D matrices. The mechanism used by human primary renal proximal tubule cells for tubulogenesis on 2D surfaces appears to be distinct from the mechanism employed in 3D gels, and tubulogenesis on 2D surfaces involves interactions between epithelial and mesenchymal cells. The process is induced by transforming growth factor-beta1, and enhanced by a 3D substrate architecture. However, after triggering the process, the formation of renal tubules occurs with remarkable independence from the substrate architecture. Human proximal tubules generated on 2D surfaces typically have a length of several millimeters, and are easily accessible for manipulations and imaging, which makes them attractive for basic research and in vitro nephrotoxicology. The experimental system described also allows for in vitro studies on how primary human kidney cells regenerate renal structures after organ disruption. The finding that human kidney cells organize tissue-like structures independently from the substrate architecture has important consequences for kidney tissue engineering, and it will be important, for instance, to inhibit the process of tubulogenesis on 2D surfaces in bioartificial kidneys. PMID: 20586829 [PubMed - as supplied by publisher] | | |
| Intrinsic properties and external factors determine differentiation bias of human embryonic stem cell lines.
July 1, 2010 at 10:36 AM
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| | Intrinsic properties and external factors determine differentiation bias of human embryonic stem cell lines. Cell Biol Int. 2010 Jun 30; Authors: Mehta A, Mathew S, Viswanathan C, Sen Majumdar A A major goal of human embryonic stem cell (hESC) research is to regulate differentiation through external means to generate specific cell types with high purity for regenerative medicine applications. Although all hESC lines express pluripotency-associated genes, their differentiation ability to various lineages differs considerably. In this report, we compared spontaneous differentiation propensity of two hESC lines, RelicellhES1 and BG01. Spontaneous differentiation of hESC lines grown in different media conditions, followed by differentiation using two methods was performed. Kinetic data generated by real time gene expression studies for differentiated cell types were analyzed, and further confirmed at protein levels. Both cell lines showed up regulation of genes associated with the three germ layers although stark contrast was evident in the magnitude of up regulation of lineage specific genes. Furthermore, a distinct difference was noticed in the rate at which the pluripoteny factors, Oct-4 and Nanog were down regulated during differentiation. Once differentiation was initiated, both Oct-4 and Nanog gene expression drastically reduced in RelicellhES1 while gradual decrease of these was observed in BG01. Our findings show a clear trend for RelicellhES1 to differentiate into neuroectodermal and mesenchymal lineages whereas BG01 cells are more prone to mesoderm and endoderm development. In addition, for certain types of differentiated cells, suspension versus plated method of culture significantly influenced the outcome of differentiation. Results obtained by spontaneous differentiation of hESCs were further amplified by induced differentiation. Thus, differential rate of down regulation of pluripotency markers along with culture conditions seems to play important role in determining the developmental bias of human ES cell lines. PMID: 20586725 [PubMed - as supplied by publisher] | | |
| A Collagen-Chitosan Hydrogel for Endothelial Differentiation and Angiogenesis( * ).
July 1, 2010 at 10:36 AM
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| | A Collagen-Chitosan Hydrogel for Endothelial Differentiation and Angiogenesis( * ). Tissue Eng Part A. 2010 Jun 29; Authors: Deng C, Zhang P, Vulesevic B, Kuraitis D, Li F, Yang AF, Griffith M, Ruel M, Suuronen EJ Cell therapy for the treatment of cardiovascular disease has been hindered by low cell engraftment, poor survival, and inadequate phenotype and function. In this study, we added chitosan to a previously developed injectable collagen matrix, with the aim of improving its properties for cell therapy and neovascularization. Different ratios of collagen and chitosan were mixed and chemically crosslinked to produce hydrogels. Swell and degradation assays showed that chitosan improved the stability of the collagen hydrogel. In culture, endothelial cells formed significantly more vascular-like structures on collagen-chitosan than collagen-only matrix. While the differentiation of circulating progenitor cells to CD31(+) cells was equal on all matrices, vascular endothelial-cadherin expression was increased on the collagen-chitosan matrix, suggesting greater maturation of the endothelial cells. In addition, the collagen-chitosan matrix supported a significantly greater number of CD133(+) progenitor cells than the collagen-only matrix. In vivo, subcutaneously implanted collagen-chitosan matrices stimulated greater vascular growth and recruited more von Willebrand factor (vWF(+)) and CXCR4(+) endothelial/angiogenic cells than the collagen-only matrix. These results indicate that the addition of chitosan can improve the physical properties of collagen matrices, and enhance their ability to support endothelial cells and angiogenesis for use in cardiovascular tissue engineering applications. PMID: 20586613 [PubMed - as supplied by publisher] | | |
| A rolled sheet of collagen gel with cultured Schwann cells: model of nerve conduit to enhance neurite growth.
July 1, 2010 at 10:36 AM
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| | A rolled sheet of collagen gel with cultured Schwann cells: model of nerve conduit to enhance neurite growth. J Biosci Bioeng. 2010 May;109(5):512-8 Authors: Goto E, Mukozawa M, Mori H, Hara M We prepared a rolled sheet of collagen gel with cultured mouse Schwann cells (SCs) as a nerve conduit (a medical device for neurosurgeons to repair an injured peripheral nerve). PC12 cells and dorsal root ganglion (DRG) cells were used as neuronal cells for evaluating the neurite growth-promoting activity of the device. As a control, we compared the rolled device with a rod device. Those neuronal cells inoculated at the terminal part of the rolled device migrated into the central part along the inter-layer space of the collagen gel layer, and then differentiated into neurons, extending many neurites for 3-12 days in culture. Significantly, this migration of neuronal cells into the device and their subsequent neurite growth was not observed in the absence of the SCs. We conclude that our rolled sheet of collagen gel with SCs was well designed and very effective to promote neurite growth, and is a promising candidate for the nerve conduit. PMID: 20347776 [PubMed - indexed for MEDLINE] | | |
| AAA stent-grafts: past problems and future prospects.
July 1, 2010 at 10:36 AM
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| | AAA stent-grafts: past problems and future prospects. Ann Biomed Eng. 2010 Apr;38(4):1259-75 Authors: Desai M, Eaton-Evans J, Hillery C, Bakhshi R, You Z, Lu J, Hamilton G, Seifalian AM Endovascular aneurysm repair (EVAR) has quickly gained popularity for infrarenal abdominal aortic aneurysm repair during the last two decades. The improvement of available EVAR devices is critical for the advancement of patient care in vascular surgery. Problems are still associated with the grafts, many of which can necessitate the conversion of the patient to open repair, or even result in rupture of the aneurysm. This review attempts to address these problems, by highlighting why they occur and what the failings of the currently available stent grafts are, respectively. In addition, the review gives critical appraisal as to the novel methods required for dealing with these problems and identifies the new generation of stent grafts that are being or need to be designed and constructed in order to overcome the issues that are associated with the existing first- and second-generation devices. PMID: 20162359 [PubMed - indexed for MEDLINE] | | |
| The effect of intermittent static biaxial tensile strains on tissue engineered cartilage.
July 1, 2010 at 10:36 AM
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| | The effect of intermittent static biaxial tensile strains on tissue engineered cartilage. Ann Biomed Eng. 2010 Apr;38(4):1672-82 Authors: Fan JC, Waldman SD Mechanical stimulation of engineered cartilage constructs is a commonly applied method used to accelerate tissue formation and improve the mechanical properties of the developed tissue. While the effects of compression and shear have been widely studied, the effect of tension has received relatively little attention. As articular cartilage in vivo is subjected to a degree of static tension (pre-tension) even in the absence of externally applied loads, the purpose of this study was to investigate the effect of intermittent static biaxial tensile strains (BTS) on chondrocyte metabolism and resultant tissue formation. Using a custom-design loading fixture to apply BTS, the optimal conditions for stimulating extracellular matrix synthesis were under average magnitudes of 3.8% radial and 2.1% circumferential tensile strains for 30 min. Tissue constructs subjected to tensile strain stimulation 3 times/week for a period of 4 weeks displayed increased thickness (35 +/- 18%) and proteoglycan content (22 +/- 7%) without an associated change in mechanical properties. In contrast, constructs stimulated daily over the same time period exhibited negligible effects in terms of ECM accumulation suggesting that the frequency of stimulation needs to be precisely controlled. The results of this study demonstrate that while tension can be used as potential biomechanical stimulus to improve tissue formation, further optimization of this process needs to be conducted to improve ECM accumulation and tissue mechanical properties after long-term exposure to tensile stimuli. PMID: 20087771 [PubMed - indexed for MEDLINE] | | |
| Numerical analysis of ischemia- and compression-induced injury in tissue-engineered skeletal muscle constructs.
July 1, 2010 at 10:36 AM
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| | Numerical analysis of ischemia- and compression-induced injury in tissue-engineered skeletal muscle constructs. Ann Biomed Eng. 2010 Mar;38(3):570-82 Authors: Ceelen KK, Gawlitta D, Bader DL, Oomens CW Pressure-related deep tissue injury may develop in skeletal muscle tissue which is subjected to prolonged compression. For early detection, it is important to understand the underlying damage processes. Gawlitta et al. [Gawlitta, D., C. W. J. Oomens, D. L. Bader, F. P. T. Baaijens, and C. V. C. Bouten. Temporal differences in the influence of ischemic factors and deformation on the metabolism of engineered skeletal muscle. J. Appl. Physiol. 103(2):464-473, 2007b] subjected tissue-engineered muscle constructs to ischemia and deformation to study their effects on viability. Contrary to previous findings, no decrease in viability was found due to compression. However, the nature of their measurement method complicated interpretation of the results, particulary when deformation was involved. Changes in the constructs were assessed by measurements in the surrounding medium. The theoretical model developed in the present study describes metabolism, diffusion, and cell death in the experiments, and accounts for reduced diffusion due to compression. It was demonstrated that the lack of effect of compression on tissue viability, as measured in the experiments, could be explained by the compression-induced decrease in diffusivity. Compression did lead to considerable cell death but this could not be measured by Gawlitta et al. [Gawlitta, D., C. W. J. Oomens, D. L. Bader, F. P. T. Baaijens, and C. V. C. Bouten. Temporal differences in the influence of ischemic factors and deformation on the metabolism of engineered skeletal muscle. J. Appl. Physiol. 103(2):464-473, 2007b] because diffusion of the cell death marker to the medium was limited. This study shows that a proper description of transport processes is essential for a correct interpretation of experiments in which indirect measurement methods are used. PMID: 20013157 [PubMed - indexed for MEDLINE] | | |
| Effect of endothelium mimicking self-assembled nanomatrices on cell adhesion and spreading of human endothelial cells and smooth muscle cells.
July 1, 2010 at 10:36 AM
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| | Effect of endothelium mimicking self-assembled nanomatrices on cell adhesion and spreading of human endothelial cells and smooth muscle cells. Nanomedicine. 2010 Apr;6(2):289-97 Authors: Andukuri A, Minor WP, Kushwaha M, Anderson JM, Jun HW The goal of this study is to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles (PAs) through a solvent evaporation technique. Three PAs, one containing the Tyr-Ile-Gly-Ser-Arg (YIGSR) ligand, the second containing the Val-Ala-Pro-Gly (VAPG) ligand, and a third without cell adhesive ligands, were developed. Cell adhesion and spreading were evaluated by a PicoGreen-DNA assay and live/dead assay, respectively. Our results show that PA-YIGSR significantly enhances HUVEC adhesion (26,704 +/- 2708), spreading (84 +/- 8%), and proliferation (50 +/- 2%) compared with that of other PAs. PA-VAPG and PA-YIGSR showed significantly greater AoSMC adhesion compared with that of PA-S. PA-VAPG also showed significantly greater spreading of AoSMCs (63 +/- 11%) compared with that of other PAs. Also, all the PAs showed significantly reduced platelet adhesion compared with that of collagen I (control). These findings would facilitate the development of novel vascular grafts, heart valves, and cell-based therapies for cardiovascular diseases. FROM THE CLINICAL EDITOR: The goal of this study was to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles through a solvent evaporation technique. The findings are expected to facilitate the development of novel vascular grafts, heart valves, and cell based therapies for cardiovascular diseases. PMID: 19800987 [PubMed - indexed for MEDLINE] | | |
| A comparison of the effects of fibre alignment of smooth and textured fibres in electrospun membranes on fibroblast cell adhesion.
July 1, 2010 at 5:36 AM
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| | A comparison of the effects of fibre alignment of smooth and textured fibres in electrospun membranes on fibroblast cell adhesion. Biomed Mater. 2010 Apr;5(2):25005 Authors: Truong YB, Glattauer V, Lang G, Hands K, Kyratzis IL, Werkmeister JA, Ramshaw JA A polyester polycaprolactone-based polyurethane elastomer (PU) and poly-(l-lactide) (PLLA), two common biomaterials, were electrospun to produce membranes with fibres either randomly orientated or aligned. PU was used to produce membranes consisting of smooth fibres. PLLA was used to prepare fibres with a textured surface. Contact angle measurements of the PU and PLLA cast films reveal that they were both below 90 degrees and fully wetted in less than 60 s. These membranes were investigated for the effect of fibre topography and fibre alignment on cell adhesion, using mouse L929 fibroblasts. It was found that the alignment of electrospun fibres controls the directional spreading of fibroblast independent of fibre being smooth or textured. PMID: 20308775 [PubMed - indexed for MEDLINE] | | | | 
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