|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Adipose-derived stem cells and their potential to differentiate into the epithelial lineage. Stem Cells Dev. 2011 Apr 17; Authors: Baer PC Adipose-derived stem cells (ASCs) possess a multilineage differentiation potential, can be used from an autologous origin and are, therefore, attractive candidates for clinical applications to repair or regenerate damaged tissues and organs. Adipose tissue as a stem cell source is ubiquitously available and has several advantages compared to other sources. It is easily accessible in large quantities with a minimal invasive harvesting procedure and the isolation of ASCs yields a high amount of stem cells, which is essential for stem cell-based therapies and tissue engineering. Differentiation of ASCs into cell types of mesodermal origin has been shown in a variety of studies. The plasticity of ASCs towards cells of the mesodermal lineage has been shown by their differentiation into chondrocytes, osteoblasts, adipocytes, and myocytes. Their potential to differentiate into lineages with non-mesodermal origin is even more exciting: ASCs are also able to differentiate into cells of ecto- and endodermal origin. Various in vitro and in vivo studies documented the induced differentiation into neural cells, hematopoietic supporting cells, hepatocytes, pancreatic islet cells, endothelial cells, and epithelial cells. Epithelial cells can embryologically arise from each of the three germ layers. This article summarizes and discusses the current knowledge of the potential of ASCs to differentiate into the epithelial lineage. The differentiation of ASCs into different types of epithelial cells including hepatocytes, pancreatic cells and endothelial cells is highlighted together with a view on current clinical trials and future options. PMID: 21495915 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury. Nephrol Dial Transplant. 2010 Dec;25(12):3874-84 Authors: Feng Z, Ting J, Alfonso Z, Strem BM, Fraser JK, Rutenberg J, Kuo HC, Pinkernell K Acute kidney injury (AKI) represents a major clinical problem with high mortality and limited causal treatments. The use of cell therapy has been suggested as a potential modality to improve the course and outcome of AKI. PMID: 20921297 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose-derived stem cells from the brown bear (Ursus arctos) spontaneously undergo chondrogenic and osteogenic differentiation in vitro. Stem Cell Res. 2011 Mar 24; Authors: Fink T, Rasmussen JG, Emmersen J, Pilgaard L, Fahlman A, Brunberg S, Josefsson J, Arnemo JM, Zachar V, Swenson JE, Fröbert O In the den, hibernating brown bears do not develop tissue atrophy or organ damage, despite almost no physical activity. Mesenchymal stem cells could play an important role in tissue repair and regeneration in brown bears. Our objective was to determine if adipose tissue-derived stem cells (ASCs) can be recovered from wild Scandinavian brown bears and characterize their differentiation potential. Following immobilization of wild brown bears 7-10days after leaving the den in mid-April, adipose tissue biopsies were obtained. ASCs were recovered from 6 bears, and shown to be able to undergo adipogenesis and osteogenesis in monolayer cultures and chondrogenesis in pellet cultures. Remarkably, when grown in standard cell culture medium in monolayer cultures, ASCs from yearlings spontaneously formed bone-like nodules surrounded by cartilaginous deposits, suggesting differentiation into osteogenic and chondrogenic lineages. This ability appears to be lost gradually with age. This is the first study to demonstrate stem cell recovery and growth from brown bears, and it is the first report of ASCs spontaneously forming extracellular matrix characteristic of bone and cartilage in the absence of specific inducers. These findings could have implications for the use of hibernating brown bears as a model to study disuse osteoporosis. PMID: 21497574 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose tissue-derived stem cells: can impure cell preparations give pure results? Nephrol Dial Transplant. 2010 Dec;25(12):3805-7 Authors: Reinders ME, Rabelink TJ PMID: 20966189 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Human relevance of pre-clinical studies in stem cell therapy; systematic review and meta-analysis of large animal models of ischemic heart disease. Cardiovasc Res. 2011 Apr 14; Authors: van der Spoel TI, Jansen Of Lorkeers SJ, Agostoni P, van Belle E, Gyöngyösi M, Sluijter JP, Cramer MJ, Doevendans PA, Chamuleau SA Aims Stem cell therapy is a treatment strategy for ischemic heart disease in patients. Meta-analysis of randomized human trials showed <5% improvement in left ventricular ejection fraction (LVEF). Meta-analysis of available pre-clinical data of ischemic heart disease could provide important clues to design human clinical trials. Methods and results Random-effects meta-analysis was performed on pig, dog or sheep studies investigating the effect of cardiac stem cell therapy in ischemic cardiomyopathy (52 studies; N=888 animals). Endpoints were LVEF and death. Ischemia/reperfusion infarction was performed in 23 studies and chronic occlusion in 29 studies. Pooled analysis showed a LVEF difference of 7.5% at follow-up after cell therapy vs. control (95% confidence interval (CI), 6.2% to 8.9%; P<0.001). By exploratory multivariable meta-regression significant predictors of LVEF improvement were: cell type (bone marrow mononuclear cells (BM-MNC) showed less effect than other cell types, e.g. mesenchymal stem cells; P=0.040) and type of infarction (left anterior descending artery 8.0% vs. left circumflex artery 5.8%; P=0.045). Cell therapy was not associated with increased mortality (P=0.68). Sensitivity analysis showed trends towards more improvement with higher cell number (≥10(7)), chronic occlusion models and late injections (>1 week). After follow-up of 8 weeks the effect of cell therapy decreased to 6%. Conclusions This meta-analysis showed that large animal models are valid to predict outcome of clinical trials. Our results showed that cell therapy is safe and led to a preserved LVEF. Future trials should focus on cell types other than BM-MNC, large infarction and strategies to obtain sustained effects overtime. PMID: 21498423 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Advances and Perspectives on Stem Cell Therapy for Human Neurodegenerative Diseases. CNS Neurol Disord Drug Targets. 2011 Apr 18; Authors: Chen LW PMID: 21495958 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem Cell Therapy for Alzheimer's Disease. CNS Neurol Disord Drug Targets. 2011 Apr 18; Authors: Abdel-Salam OM Alzheimer's disease (AD) is a progressive neurodegenerative disorder which impairs the memory and intellectual abilities of the affected individuals. Loss of episodic as well as semantic memory is an early and principal feature. The basal forebrain cholinergic system is the population of neurons most affected by the neurodegenerative process. Extracellular as well as intracellular deposition of beta-amyloid or Abeta (A) protein, intracellular formation of neurofibrillary tangles and neuronal loss are the neuropathological hallmarks of AD. In the last few years, hopes were raised that cell replacement therapy would provide cure by compensating the lost neuronal systems. Stem cells obtained from embryonic as well as adult tissue and grafted into the intact brain of mice or rats were mostly followed by their incorporation into the host parenchyma and differentiation into functional neural lineages. In the lesioned brain, stem cells exhibited targeted migration towards the damaged regions of the brain, where they engrafted, proliferated and matured into functional neurones. Neural precursor cells can be intravenously administered and yet migrate into brain damaged areas and induce functional recovery. Observations in animal models of AD have provided evidence that transplanted stem cells or neural precursor cells (NPCs) survive, migrate, and differentiate into cholinergic neurons, astrocytes, and oligodendrocytes with amelioration of the learning/memory deficits. Besides replacement of lost or damaged cells, stem cells stimulate endogenous neural precursors, enhance structural neuroplasticity, and down regulate proinflammatory cytokines and neuronal apoptotic death. Stem cells could also be genetically modified to express growth factors into the brain. In the last years, evidence indicated that the adult brain of mammals preserves the capacity to generate new neurons from neural stem/progenitor cells. Inefficient adult neurogenesis may contribute to the pathogenesis of AD and other neurodegenerative disorders. An attempt at mobilizing this endogenous pool of resident stem-like cells provides another attractive approach for the treatment of AD. Studies in patients with AD indicated decreased hippocampal volume derived by neurodegeneration. Intriguingly, many drugs including antidepressants, lithium, acetyl cholinesterase inhibitors, and ginkgo biloba, were able to enhance the impaired neurogenesis in this disease process. This paved the way towards exploring the possible pharmacological manipulation of neurogenesis which would offer an alternative approach for the treatment of AD. PMID: 21495961 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Potential Application of Induced Pluripotent Stem Cells in Cell Replacement Therapy for Parkinson's Disease. CNS Neurol Disord Drug Targets. 2011 Apr 18; Authors: Chen LW, Kuang F, Wei LC, Ding YX, Yung KK, Chan YS Parkinson's disease (PD), a common degenerative disease in humans, is known to result from loss of dopamine neurons in the substantia nigra and is characterized by severe motor symptoms of tremor, rigidity, bradykinsia and postural instability. Although levodopa administration, surgical neural lesion, and deep brain stimulation have been shown to be effective in improving parkinsonian symptoms, cell replacement therapy such as transplantation of dopamine neurons or neural stem cells has shed new light on an alternative treatment strategy for PD. While the difficulty in securing donor dopamine neurons and the immuno-rejection of neural transplants largely hinder application of neural transplants in clinical treatment, induced pluripotent stem cells (iPS cells) derived from somatic cells may represent a powerful tool for studying the pathogenesis of PD and provide a source for replacement therapies in this neurodegenerative disease. Yamanaka et al. [2006, 2007] first succeeded in generating iPS cells by reprogramming fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c-Myc in both mouse and human. Animal studies have further shown that iPS cells from fibroblasts could be induced into dopamine neurons and transplantation of these cells within the central nervous system improved motor symptoms in the 6-OHDA model of PD. More interestingly, neural stem cells or fibroblasts from patients can be efficiently reprogrammed and subsequently differentiated into dopamine neurons. Derivation of patient-specific iPS cells and subsequent differentiation into dopamine neurons would provide a disease-specific in vitro model for disease pathology, drug screening and personalized stem cell therapy for PD. This review summarizes current methods and modifications in producing iPS cells from somatic cells as well as safety concerns of reprogramming procedures. Novel reprogramming strategies that deter abnormal permanent genetic and epigenetic alterations are essential for propagating clinically-qualified iPS cells. Future investigations into cell transforming and reprogramming processes are needed to generate the disease-specific iPS cells for personalized regeneration medicine of PD patients by disclosing detailed reprogramming mechanisms. PMID: 21495962 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Towards the creation of decellularized organ constructs using irreversible electroporation and active mechanical perfusion. Biomed Eng Online. 2010;9:83 Authors: Sano MB, Neal RE, Garcia PA, Gerber D, Robertson J, Davalos RV Despite advances in transplant surgery and general medicine, the number of patients awaiting transplant organs continues to grow, while the supply of organs does not. This work outlines a method of organ decellularization using non-thermal irreversible electroporation (N-TIRE) which, in combination with reseeding, may help supplement the supply of organs for transplant. PMID: 21143979 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose-derived stem cells and their potential to differentiate into the epithelial lineage. Stem Cells Dev. 2011 Apr 17; Authors: Baer PC Adipose-derived stem cells (ASCs) possess a multilineage differentiation potential, can be used from an autologous origin and are, therefore, attractive candidates for clinical applications to repair or regenerate damaged tissues and organs. Adipose tissue as a stem cell source is ubiquitously available and has several advantages compared to other sources. It is easily accessible in large quantities with a minimal invasive harvesting procedure and the isolation of ASCs yields a high amount of stem cells, which is essential for stem cell-based therapies and tissue engineering. Differentiation of ASCs into cell types of mesodermal origin has been shown in a variety of studies. The plasticity of ASCs towards cells of the mesodermal lineage has been shown by their differentiation into chondrocytes, osteoblasts, adipocytes, and myocytes. Their potential to differentiate into lineages with non-mesodermal origin is even more exciting: ASCs are also able to differentiate into cells of ecto- and endodermal origin. Various in vitro and in vivo studies documented the induced differentiation into neural cells, hematopoietic supporting cells, hepatocytes, pancreatic islet cells, endothelial cells, and epithelial cells. Epithelial cells can embryologically arise from each of the three germ layers. This article summarizes and discusses the current knowledge of the potential of ASCs to differentiate into the epithelial lineage. The differentiation of ASCs into different types of epithelial cells including hepatocytes, pancreatic cells and endothelial cells is highlighted together with a view on current clinical trials and future options. PMID: 21495915 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor α1 in Mesenchymal Stem Cells. Tohoku J Exp Med. 2011;224(1):7-12 Authors: Huang J, Deng F, Wang L, Xiang XR, Zhou WW, Hu N, Xu L Mesenchymal stem sells (MSCs) have received much attention in the field of bone tissue engineering due to their biological capability to differentiate into osteogenic lineage cells. Hypoxia-inducible factor 1alpha (HIF-1α) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfα1) is a transcription regulator that is involved in the chondrocyte differentiation and ossification. In the present study, we investigated the effects of hypoxia on biological capability of MSCs. MSCs were isolated from adult rabbit bone marrow, and were cultured in vitro under normoxia (air with 5% CO(2)) or hypoxia (5% CO(2) and 95% N(2)). The proliferation of MSCs, alkaline phosphatase (ALP) activity, and production of collagens type I and type III (Col I/III) were examined. The expression levels of HIF-1α and Cbfα1 were measured by real-time PCR and western blot analyses. We found that hypoxia significantly induced the proliferation of MSCs and increased ALP activity and the production of Col I/III. Moreover, hypoxia increased the expression of Cbfα1 mRNA after 12 h, whereas the expression of HIF-1α mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1α expression with a small interfering RNA significantly increased the expression levels of Cbfα1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfα1 may be negatively regulated by HIF-1α. PMID: 21498965 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Enzyme-assisted purification of denatured atelocollagen, using pronase as scavenging agent. Rev Med Chir Soc Med Nat Iasi. 2010 Oct-Dec;114(4):1232-9 Authors: Maier SS, Maier V, Popa M, Ignat CM Collagen liquid-crystal characteristics can be exploited in advanced applications, like microelectromechanical systems (MEMS), collagen-silica biohybrids or intelligent substrates for tissue engineering. Such applications necessarily require high purity of the collagen colloidal solutions, in terms of macromolecular unitary composition, which is equivalent to almost zero poydispersity. In this work a protocol for the enzyme-assisted removal of non-triple helical polypeptide entities in atelocollagen solutions was conceived, using pronase as scavenger, in the presence of poly(ethyleneglycol) (PEG 10000) as a crowding agent, trimethylamine-N-oxide dihydrate, (TMAO) as kosmotropic agent and anhydrous sodium sulfate as anti-chaotrope salt. Unusually high enzyme concentration (3 : 100 w/w 5 U/mg Pronase : total dry protein) imposes the triple-helix integrity protection, which was achieved by means of protective adjuvants. The adjuvant agents mixture comprising the crowder, the kosmotrope and the anti-chaotropic salt, was formulated according to the Design of Experiments (DOE) principles. The crowding agent represents the key factor in modulating pronase hydrolytic action upon atelocollagen substrate. The optimal adjuvant mixture tested in order to confirm the model validity had the composition: 0.675 PEG, 0.200 TMAO, 0.125 Na2SO4 (mass fractions). The proposed protocol is suitable for purifying medium and large quantities of atelocollagen previously solubilized through an alkali-enzyme technique. PMID: 21495461 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Substrate stiffness influences high resolution printing of living cells with an ink-jet system. J Biosci Bioeng. 2011 Apr 14; Authors: Tirella A, Vozzi F, De Maria C, Vozzi G, Sandri T, Sassano D, Cognolato L, Ahluwalia A The adaptation of inkjet printing technology for the realisation of controlled micro- and nano-scaled biological structures is of great potential in tissue and biomaterial engineering. In this paper we present the Olivetti BioJet system and its applications in tissue engineering and cell printing. BioJet, which employs a thermal inkjet cartridge, was used to print biomolecules and living cells. It is well known that high stresses and forces are developed during the inkjet printing process. When printing living particles (i.e., cell suspensions) the mechanical loading profile can dramatically damage the processed cells. Therefore computational models were developed to predict the velocity profile and the mechanical load acting on a droplet during the printing process. The model was used to investigate the role of the stiffness of the deposition substrate during droplet impact and compared with experimental investigations on cell viability after printing on different materials. The computational model and the experimental results confirm that impact forces are highly dependent on the deposition substrate and that soft and viscous surfaces can reduce the forces acting on the droplet, preventing cell damage. These results have high relevance for cell bioprinting; substrates should be designed to have a good compromise between substrate stiffness to conserve spatial patterning without droplet coalescence but soft enough to absorb the kinetic energy of droplets in order to maintain cell viability. PMID: 21497548 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | 3D tumour models: novel in vitro approaches to cancer studies. J Cell Commun Signal. 2011 Apr 16; Authors: Nyga A, Cheema U, Loizidou M 3D in vitro models have been used in cancer research as a compromise between 2-dimensional cultures of isolated cancer cells and the manufactured complexity of xenografts of human cancers in immunocompromised animal hosts. 3D models can be tailored to be biomimetic and accurately recapitulate the native in vivo scenario in which they are found. These 3D in vitro models provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations. Approaches to create more biomimetic 3D models of cancer include, but are not limited to, (i) providing the appropriate matrix components in a 3D configuration found in vivo, (ii) co-culturing cancer cells, endothelial cells and other associated cells in a spatially relevant manner, (iii) monitoring and controlling hypoxia- to mimic levels found in native tumours and (iv) monitoring the release of angiogenic factors by cancer cells in response to hypoxia. This article aims to overview current 3D in vitro models of cancer and review strategies employed by researchers to tackle these aspects with special reference to recent promising developments, as well as the current limitations of 2D cultures and in vivo models. 3D in vitro models provide an important alternative to both complex in vivo whole organism approaches, and 2D culture with its spatial limitations. Here we review current strategies in the field of modelling cancer, with special reference to advances in complex 3D in vitro models. PMID: 21499821 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bioreactor systems for bone tissue engineering. Tissue Eng Part B Rev. 2011 Apr 17; Authors: Rauh J, Milan F, Günther KP, Stiehler M Bone graft material is often required for the treatment of osseous defects. However, due to limitations and risks associated with autologous as well as allogenic bone grafting procedures, alternative strategies are needed. In this context, ex vivo tissue engineering strategies for de novo generation of bone tissue include the combined use of autologous bone-forming cells and 3D porous scaffold materials serving as structural support for the cells. 3D cultivation of osteoprogenitor cells presents several challenges, e.g. insufficient nutrient and oxygen transport to and removal of waste products from the cells at the interior of the scaffold. By providing physical stimulation of tissue-engineered constructs and resolving mass transport limitations bioreactor systems denote key components for bone tissue engineering strategies. A variety of dynamic 3D bioreactor concepts mimicking the native microenvironment in bone tissue, e.g. spinner flasks, rotating wall vessel constructs, perfusion bioreactors and systems based on mechanical or electromagnetic stimulation of cell/scaffold composites, have been developed. These techniques differ considerably with respect to ease of use, cost-effectiveness, and degree of additional osteogenic stimuli, as well as monitoring and manipulation options. This review provides an overview of the concepts, advantages, challenges, and potential future applications associated with current bioreactor systems for bone tissue engineering. PMID: 21495897 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adhesion, proliferation and differentiation of pluripotent stem cells on multi-walled carbon nanotubes. IET Nanobiotechnol. 2011 Jun;5(2):41 Authors: Holy J, Perkins E, Yu X This article studies the adhesion, growth and differentiation of stem cells on carbon nanotube matrices. Glass coverslips were coated with multi-walled carbon nanotube (MWNT) thin films using layer-by-layer self-assembling techniques. Pluripotent P19 mouse embryonal carcinoma stem cells were seeded onto uncoated or MWNT-coated glass coverslips and either maintained in an undifferentiated state or induced to differentiate by the addition of retinoic acid. The authors found that cell adhesion was increased on the MWNT-coated glass surfaces, and that the expression patterns of some differentiation markers were altered in cells grown on MWNTs. The results suggest that MWNTs will be useful in directing pluripotent stem cell differentiation for tissue engineering purposes. PMID: 21495779 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Electrospun chitosan-graft-poly (ɛ-caprolactone)/poly (ɛ-caprolactone) nanofibrous scaffolds for retinal tissue engineering. Int J Nanomedicine. 2011;6:453-61 Authors: Chen H, Fan X, Xia J, Chen P, Zhou X, Huang J, Yu J, Gu P A promising therapy for retinal diseases is to employ biodegradable scaffolds to deliver retinal progenitor cells (RPCs) for repairing damaged or diseased retinal tissue. In the present study, cationic chitosan-graft-poly(ɛ-caprolactone)/polycaprolactone (CS-PCL/PCL) hybrid scaffolds were successfully prepared by electrospinning. Characterization of the obtained nanofibrous scaffolds indicated that zeta-potential, fiber diameter, and the content of amino groups on their surface were closely correlated with the amount of CS-PCL in CS-PCL/PCL scaffolds. To assess the cell-scaffold interaction, mice RPCs (mRPCs) were cultured on the electrospun scaffolds for 7 days. In-vitro proliferation assays revealed that mRPCs proliferated faster on the CS-PCL/PCL (20/80) scaffolds than the other electrospun scaffolds. Scanning electron microscopy and the real-time quantitative polymerase chain reaction results showed that mRPCs grown on CS-PCL/PCL (20/80) scaffolds were more likely to differentiate towards retinal neurons than those on PCL scaffolds. Taken together, these results suggest that CS-PCL/PCL(20/80) scaffolds have potential application in retinal tissue engineering. PMID: 21499434 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Fibroblast growth factor 9 delivery during angiogenesis produces durable, vasoresponsive microvessels wrapped by smooth muscle cells. Nat Biotechnol. 2011 Apr 17; Authors: Frontini MJ, Nong Z, Gros R, Drangova M, O'Neil C, Rahman MN, Akawi O, Yin H, Ellis CG, Pickering JG The therapeutic potential of angiogenic growth factors has not been realized. This may be because formation of endothelial sprouts is not followed by their muscularization into vasoreactive arteries. Using microarray expression analysis, we discovered that fibroblast growth factor 9 (FGF9) was highly upregulated as human vascular smooth muscle cells (SMCs) assemble into layered cords. FGF9 was not angiogenic when mixed with tissue implants or delivered to the ischemic mouse hind limb, but instead orchestrated wrapping of SMCs around neovessels. SMC wrapping in implants was driven by sonic hedgehog-mediated upregulation of PDGFRβ. Computed tomography microangiography and intravital microscopy revealed that microvessels formed in the presence of FGF9 had enhanced capacity to receive flow and were vasoreactive. Moreover, the vessels persisted beyond 1 year, remodeling into multilayered arteries paired with peripheral nerves. This mature physiological competency was attained by targeting mesenchymal cells rather than endothelial cells, a finding that could inform strategies for therapeutic angiogenesis and tissue engineering. PMID: 21499246 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Synthesis of fluorapatite-hydroxyapatite nanoparticles and toxicity investigations. Int J Nanomedicine. 2011;6:197-201 Authors: Montazeri N, Jahandideh R, Biazar E In this study, calcium phosphate nanoparticles with two phases, fluorapatite (FA; Ca(10)(PO(4))(6)F(2)) and hydroxyapatite (HA; Ca(10)(PO(4))(6)(OH)(2)), were prepared using the solgel method. Ethyl phosphate, hydrated calcium nitrate, and ammonium fluoride were used, respectively, as P, Ca, and F precursors with a Ca:P ratio of 1:72. Powders obtained from the sol-gel process were studied after they were dried at 80°C and heat treated at 550°C. The degree of crystallinity, particle and crystallite size, powder morphology, chemical structure, and phase analysis were investigated by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and Zetasizer experiments. The results of XRD analysis and FTIR showed the presence of hydroxyapatite and fluorapatite phases. The sizes of the crystallites estimated from XRD patterns using the Scherrer equation and the crystallinity of the hydroxyapatite phase were about 20 nm and 70%, respectively. Transmission electron microscope and SEM images and Zetasizer experiments showed an average size of 100 nm. The in vitro behavior of powder was investigated with mouse fibroblast cells. The results of these experiments indicated that the powders were biocompatibile and would not cause toxic reactions. These compounds could be applied for hard-tissue engineering. PMID: 21499417 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Liver fibrogenic cells. Best Pract Res Clin Gastroenterol. 2011 Apr;25(2):207-17 Authors: Forbes SJ, Parola M Liver fibrogenic cells are a heterogenous population of cells that include α-smooth muscle actin positive myofibroblasts (MFs). MFs promote the progression of chronic liver diseases (CLDs) towards cirrhosis. MFs are highly proliferative and contractile and promote fibrogenesis by means of their multiple phenotypic responses to injury. These include: excess deposition and altered remodelling of extracellular matrix; the synthesis and release of growth factor which sustain and perpetuate fibrogenesis; chronic inflammatory response and neo-angiogenesis. MFs mainly originate from hepatic stellate cells or portal fibroblasts through activation and transdifferentiation. MFs may also potentially differentiate from bone marrow-derived stem cells. It has been suggested that MFs can be derived from hepatocytes or cholangiocytes through a process of epithelial to mesenchymal transition in the liver, however this is controversial. Hepatic MFs may also modulate the immune responses to hepatocellular carcinomas and metastatic cancers through cross talk with hepatic progenitor and tumour cells. PMID: 21497739 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Neuroprotective effects of the beta-catenin stabilization in an oxygen- and glucose-deprived human neural progenitor cell culture system. Int J Dev Neurosci. 2011 Apr 7; Authors: Skardelly M, Gaber K, Schwarz J, Milosevic J β-Catenin stabilization achieved either via GSK-3β specific inhibition or involving canonical Wnt signalling pathway, contributes to neuroprotection in an oxygen-glucose deprivation (4h OGD) in vitro hypoxia model performed on human cortical neural progenitor cells previously differentiated into neurons and glia. Neuroprotection mechanisms include both acquiring tolerance to injury throughout preconditioning (72h prior to OGD) or being pro-survival during 24h reoxygenation after the insult. Four hours of OGD induced apoptotic cell death elevation to 73±1% vs. 12% measured in control and the LDH level, indicative of necrotic cell injury, elevation by 67±7% (set to 100%). A significant reduction in apoptosis occurred at 24h reoxygenation with indirubin supplement which was 49±6% at 2.5μM BIO while LDH level was only 47±5% of OGD. Kenpaullone was efficient in reducing both cell deaths at 5μM (apoptosis 38±1% and necrosis 33±3% less than in OGD). Wnt agonist reduced apoptosis to 45±3% at 0.01μM, while LDH value was decreased to a level of 53±5% of control. Our findings suggest that GSK-3beta inhibitors/β-catenin stabilizers may ultimately be useful drugs in neuroprotection and neuroregeneration therapies in vivo. PMID: 21497193 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Decreased expression of p63, a regulator of epidermal stem cells, in the chronic laminitic equine hoof. Equine Vet J. 2011 Mar 11; Authors: Carter RA, Engiles JB, Megee SO, Senoo M, Galantino-Homer HL Reasons for performing study: Abnormal epidermal stem cell regulation may contribute to the pathogenesis of equine chronic laminitis. Objective: To analyse the involvement of p63, a regulator of epidermal stem cell proliferative potential, in chronic laminitis. Methods: Epidermal tissues from skin, coronet and lamellae of the dorsal foot were harvested from 5 horses with chronic laminitis and 5 control horses. Tissues were analysed using histopathology, immunofluorescence microscopy and quantitative immunoblotting Results: Hoof lamellae of laminitic horses had a lower frequency of p63 positive cells than control lamellae, particularly in the distal region. Quantitative immunoblotting confirmed reduced p63 expression in the laminitic distal lamellar region. The decreased p63 expression in laminitic epidermal lamellae was most apparent in the abaxial region adjacent to the hoof wall and highly associated with the formation of terminally differentiated, dysplastic and hyperkeratotic epidermis in this region, whereas lamellae from control horses maintained high p63 expression throughout the axial-abaxial axis. Conclusions: Expression of p63 in equine skin resembles that reported in other species, including man and rodents, suggesting that p63 can serve as a marker for the proliferative potential of equine epidermal stem cells. p63 expression was significantly lower in the chronic laminitic hoof than in that of control horses, suggesting laminitic hoof epithelium has more limited proliferative potential with a shift towards differentiation. This may reflect reduced activity of epidermal stem cells in laminitic hoof. It is proposed that p63 contributes to the maintenance of hoof lamellae and that misregulation of p63 expression may lead to epidermal dysplasia during lamellar wedge formation. Potential relevance: This study suggests that loss of epidermal stem cells contributes to the pathogenesis of equine laminitis. Autologous transplantation of p63-positive epidermal stem cells from unaffected regions may have regenerative therapeutic potential for laminitic horses. PMID: 21496086 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Generation of LIF and bFGF-Dependent Induced Pluripotent Stem Cells from Canine Adult Somatic Cells. Stem Cells Dev. 2011 Apr 17; Authors: Luo J, Suhr S, Chang EA, Wang K, Ross PJ, Nelson L, Venta P, Knott J, Cibelli JB For more than thirty years, the dog has been used as a model for human diseases. Despite efforts made to develop canine embryonic stem cells, success has been elusive. Here, we report the generation of canine induced pluripotent stem cells (ciPSCs) from canine adult fibroblasts, which we accomplished by introducing human OCT4, SOX2, c-MYC, and KLF4. The ciPSCs expressed critical pluripotency markers and showed evidence of silencing the viral vectors and normal karyotypes. Microsatellite analysis indicated that the ciPSCs showed the same profile as the donor fibroblasts but differed from cells taken from other dogs. Under culture condition favoring differentiation, the ciPSCs could form cell derivatives from the ectoderm, mesoderm, and endoderm. Further, the ciPSCs required leukemia inhibitory factor and basic fibroblast growth factor to survive, proliferate, and maintain pluripotency. Our results demonstrate an efficient method for deriving canine pluripotent stem cells, providing a powerful platform for the development of new models for regenerative medicine, as well as for the study of the onset, progression, and treatment of human and canine genetic diseases. PMID: 21495906 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Using High-Throughput Immunoblotting to Identify Proteins Involved in the Differentiation of ES Cells along the Hair Follicle Lineage in Vitro. Stem Cell Rev. 2011 Apr 16; Authors: Troy TC, Turksen K The hair follicles develop from a stem cell population in the surface ectoderm that feeds a complexe terminal differentiation pathway. We have developed a two-step high density culture scheme in which pluripotent mouse ES cells are induced first to ectoderm phenotype and then give rise to morphologically three dimensional nodule-like structures that express hair keratin in the center of them suggesting that they are progressing along the terminal differentiation program of the hair follicle in vitro. Using this model system we have now analyzed the protein expression profile using a high throughput western blotting method (BP Power Blot). This protocol provides an invaluable system in which to study both the mechanisms that direct stem cells along the hair follicle pathway as well as those that influence their subsequent epidermal differentiation in vitro. PMID: 21499705 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Wilms tumor-a renal stem cell malignancy? Pediatr Nephrol. 2011 Apr 16; Authors: Pode-Shakked N, Dekel B Wilms' tumor (WT; nephroblastoma) is the most common pediatric renal malignancy and rated fourth in overall incidence among childhood cancers. It is viewed as a prototype of differentiation failure in human neoplasia as it recapitulates the histology of the nephrogenic zone of the growing fetal kidney. The cellular origin of WT is unclear. However, recent genomic, genetic and epigenetic studies point to an early renal stem/progenitor cell that undergoes malignant transformation as the source for WT. In this context, classical WT shares genes and pathways activated in progenitors committed to the renal lineage. However, direct proof and characterization of the WT initiating cell have remained elusive. Novel methodologies recently adopted from the cancer stem cell scientific field, including the analysis of sorted single human tumor cells, have been applied to WT. These have enabled the identification of cell sub-populations that show similarities-in terms of molecular marker expression-to human fetal kidney progenitors and are, therefore, likely to be derivatives of the same lineage. Further elucidation of the WT cancer stem cell or the cell of origin in human tumors and in transgenic mouse models that generate murine tumors may not only provide novel therapeutic targets but also shed light on the normal kidney stem cell. PMID: 21499773 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Stem cell market in Hungary]. Lege Artis Med. 2010 Dec;20(12):866-71 Authors: Tóth B PMID: 21469293 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Allorecognition in a Basal Chordate Consists of Independent Activating and Inhibitory Pathways. Immunity. 2011 Apr 14; Authors: McKitrick TR, Muscat CC, Pierce JD, Bhattacharya D, De Tomaso AW Histocompatibility in the basal chordate Botryllus schlosseri is controlled by the polymorphisms of a single gene: the fuhc. A polymorphic candidate receptor (fester) appeared to play roles in both initiating the reaction and discriminating between fuhc alleles. Here we report the characterization of a related protein, uncle fester. uncle fester is not polymorphic, and although coexpressed with fester, has different functional properties. Loss-of-function studies demonstrate that uncle fester was required for incompatible reactions but has no role in interactions between compatible individuals. Furthermore, stimulation with monoclonal antibodies could initiate a rejection phenotype on a single colony, and in both assays the severity of the rejection could be manipulated. These findings suggest that allorecognition in Botryllus consists of independent pathways that control compatible and incompatible outcomes that are integrated within the interacting cells, and may provide insight into basal processes conserved in allorecognition responses throughout the metazoa. PMID: 21497115 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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