| Medaka Oct4 is expressed during early embryo development, and in primordial germ cells and adult gonads.
December 25, 2009 at 11:03 am
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| | Medaka Oct4 is expressed during early embryo development, and in primordial germ cells and adult gonads. Dev Dyn. 2009 Dec 23; Authors: Sánchez-Sánchez AV, Camp E, García-España A, Leal-Tassias A, Mullor JL Oct4 is a crucial transcription factor for controlling pluripotency in embryonic stem cells and the epiblast of mouse embryos. We have characterized the expression pattern of medaka (Oryzias latipes) Ol-Oct4 during embryonic development and in the adult gonads. Genomic analysis showed that Ol-Oct4 is the ortholog of zebrafish spg/pou2. However, their expression patterns are not the same, suggesting that Oct4 may play different roles in zebrafish and medaka. Using specific antibodies for the Ol-Oct4 protein, we showed that Ol-Oct4 is also expressed in primordial germ cells, in the spermatogonia (male germ stem cells), and during different stages of oocyte development. These results suggest that Ol-Oct4 plays a post-embryonic role in the maturing gonads and gametes. The Ol-Oct4 mRNA and protein expression patterns are similar to those of mammalian Oct4 and introduce medaka fish as a valid model for the functional and evolutionary study of pluripotency genes in vivo. Developmental Dynamics, 2010. (c) 2009 Wiley-Liss, Inc. PMID: 20034054 [PubMed - as supplied by publisher] |
| The effect of PKC activation and inhibition on osteogenic differentiation of human mesenchymal stem cells.
December 25, 2009 at 11:03 am
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| | The effect of PKC activation and inhibition on osteogenic differentiation of human mesenchymal stem cells. J Tissue Eng Regen Med. 2009 Dec 23; Authors: Liu J, Someren E, Mentink A, Licht R, Dechering K, van Blitterswijk C, de Boer J Human mesenchymal stem cells (hMSCs) are being considered for several areas of clinical therapy, due to their multipotent nature. For instance, osteogenic hMSCs are applied in bone tissue engineering, but current differentiation protocols need further optimization before they can be clinically applied. Protein kinase C (PKC) family members have been implicated in bone metabolism, which prompted us to use a pharmaceutical approach to manipulate PKC signalling in hMSCs. Inhibition of PKC resulted in a dose-dependent inhibition of dexamethasone-induced osteogenic differentiation. Surprisingly, PKC activation using phorbol 12-myristate 13-acetate (PMA) also resulted in inhibition of osteogenesis, although we observed that inhibition was more pronounced at low than at high concentrations of PMA. Furthermore, we observed that inhibition of PKCdelta blocked alkaline phosphatase (ALP, an early marker of osteogenic differentiation) expression, whereas inhibition of the conventional PKC subfamily and PKCmicro using Gö6976 resulted in an induction of ALP activity, collagen (I) expression and mineralization. In conclusion, inhibition of the conventional PKCs/PKCmicro and activation of PKCdelta could further benefit osteogenic differentiation of hMSCs in vitro and in vivo, which is currently under investigation. Copyright (c) 2009 John Wiley & Sons, Ltd. PMID: 20033927 [PubMed - as supplied by publisher] |
| Mesenchymal stem cell function on hybrid organic/inorganic microparticles in vitro.
December 25, 2009 at 11:03 am
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| | Mesenchymal stem cell function on hybrid organic/inorganic microparticles in vitro. J Tissue Eng Regen Med. 2009 Dec 23; Authors: Champa Jayasuriya A, Bhat A The aim of this study was to investigate mesenchymal stem cell (MSC) function on novel type hybrid organic/inorganic microparticles (MPs) for application to bone regeneration. The MPs were based on chitosan (CS) and consisted of inorganic components, such as dibasic calcium phosphate (CaHPO(4)) or calcium carbonate (CaCO(3)). The MPs were crosslinked using tripolyphosphate. Four types of hybrid MPs were fabricated: CS; CS-10% CaHPO(4); CS-20% CaHPO(4); and CS-10% CaCO(3). The MSCs were attached to all the types of MPs at day 1 and started to spread and proliferate further by days 2 and 7, as analysed by fluorescence microcopy. Cell proliferation was measured at days 7, 14, 21 and 28 by counting the cells attached on the MPs. The number of proliferated cells increased significantly for all types of MPs as time increased. MSC differentiation was analysed using osteoblast (OB) phenotype markers, including alkaline phosphatase activity (ALP), collagen I (COLLI) and osteocalcin (OCN) at days 7, 14, 21 and 28, using quantitative real-time PCR. The normalized mRNA expression of ALP for all MPs was observed only at day 7. The normalized mRNA expression of COLLI and OCN was significantly increased for all types of hybrid MPs at each time point compared to the control samples. Collectively, our results proved that hybrid organic/inorganic MPs were non-cytotoxic and supported MSC attachment, spreading, proliferation and differentiation into the OB phenotype. These hybrid MPs have great potential for application as bone-void fillers or bone tissue engineering scaffolds in bone regeneration. Copyright (c) 2009 John Wiley & Sons, Ltd. PMID: 20033925 [PubMed - as supplied by publisher] |
| Chitosan-based hydrogels do not induce angiogenesis.
December 25, 2009 at 11:03 am
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| | Chitosan-based hydrogels do not induce angiogenesis. J Tissue Eng Regen Med. 2009 Dec 23; Authors: Ahmadi R, Burns AJ, de Bruijn JD The aim of this study was to assess the angiogenic potential of chitosan-glycerol phosphate (GP)-hydroxyethyl cellulose (HEC) binder for injectable bone tissue engineering applications. The angiogenic response of chitosan-GP-HEC combined with and without human bone marrow-derived mesenchymal stem cells (hMSCs) was examined using the chick chorioallantoic membrane (CAM) assay. Chitosan-GP-HEC gel did not show any angiogenic potential, whereas the presence of hMSCs gave rise to an enhanced angiogenic response when placed on the CAM for 3 days. Quantitatively, significantly more blood vessel formation was observed for the stem cell-containing group as compared to all other groups (p < 0.05), except for the b-FGF-positive control. The results indicate that the chitosan-GP-HEC binder does not contribute to enhanced angiogenesis and that the presence of hMSCs enhances angiogenesis. Copyright (c) 2009 John Wiley & Sons, Ltd. PMID: 20033923 [PubMed - as supplied by publisher] |
| Newly established cell lines from mouse oral epithelium regenerate teeth when combined with dental mesenchyme.
December 25, 2009 at 11:03 am
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| | Newly established cell lines from mouse oral epithelium regenerate teeth when combined with dental mesenchyme. In Vitro Cell Dev Biol Anim. 2009 Dec 24; Authors: Takahashi C, Yoshida H, Komine A, Nakao K, Tsuji T, Tomooka Y The present study attempted to examine whether clonal cell lines of the oral epithelium can differentiate into ameloblasts and regenerate tooth when combined with dental germ mesenchyme. Clonal cell lines with a distinct morphology were established from the oral epithelium of p53-deficient fetal mice at embryonic day 18 (E18). The strain of mouse is shown to be a useful source for establishing clonal and immortalized cell lines from various tissues and at various stages of development. Tooth morphogenesis is almost completed and the oral epithelium is segregated from the dental epithelium at E18. In RT-PCR analysis of cell lines, mucosal epithelial markers (cytokeratin 14) were detected, but ameloblast markers such as amelogenin and ameloblastin were not detected when cells were cultured on plastic dish. They formed stratified epithelia and expressed a specific differentiation marker (CK13) in the upper layer when cultured on feeder layer or on collagen gel for 1-3 wk, demonstrating that they are of oral mucosa origin. Next, bioengineered tooth germs were prepared with cell lines and fetal molar mesenchymal tissues and implanted under kidney capsule for 2-3 wk. Five among six cell lines regenerated calcified structures as seen in natural tooth. Our results indicate that some oral epithelial cells at E18 possess the capability to differentiate into ameloblasts. Furthermore, cell lines established in the present study are useful models to study processes in tooth organogenesis and tooth regeneration. PMID: 20033791 [PubMed - as supplied by publisher] |
| Effect of in vitro culture on a chondrocyte-fibrin glue hydrogel for cartilage repair.
December 25, 2009 at 11:03 am
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| | Effect of in vitro culture on a chondrocyte-fibrin glue hydrogel for cartilage repair. Knee Surg Sports Traumatol Arthrosc. 2009 Dec 24; Authors: Scotti C, Mangiavini L, Boschetti F, Vitari F, Domeneghini C, Fraschini G, Peretti GM Research in tissue engineering has been focused on articular cartilage repair for more than a decade. Some pioneristic studies involved the use of hydrogels such as alginate and fibrin glue which still possess valuable potential for cartilage regeneration. One of the main issues in cartilage tissue engineering is represented by the ideal maturation of the construct, before in vivo implantation, in order to optimize matrix quality and integration. The present study was focused on the effect of in vitro culture on a fibrin glue hydrogel embedding swine chondrocytes. We performed an evaluation of the immunohistochemical and biochemical composition and of the biomechanical properties of the construct after 1 and 5 weeks of culture. We noticed that chondrocytes survived in the fibrin glue gel and enhanced their synthetic activity. In fact, DNA content remained stable, while all indices of cartilage matrix production increased (GAGs content, immunohistochemistry for collagen II and safranin-o staining). On the other hand, the biomechanical properties remained steady, indicating a gradual substitution of the hydrogel scaffold by cartilaginous matrix. This demonstrates that an optimal preculture could provide the surgeon with a better engineered cartilage for implantation. However, whether this more mature tissue will result in a more efficient regeneration of the articular surface still has to be evaluated in future investigations. PMID: 20033674 [PubMed - as supplied by publisher] |
| Probing Cell Structure Responses Through a Shear and Stretching Mechanical Stimulation Technique.
December 25, 2009 at 11:03 am
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| | Probing Cell Structure Responses Through a Shear and Stretching Mechanical Stimulation Technique. Cell Biochem Biophys. 2009 Dec 22; Authors: Steward RL, Cheng CM, Wang DL, Leduc PR Cells are complex, dynamic systems that respond to various in vivo stimuli including chemical, mechanical, and scaffolding alterations. The influence of mechanics on cells is especially important in physiological areas that dictate what modes of mechanics exist. Complex, multivariate physiological responses can result from multi-factorial, multi-mode mechanics, including tension, compression, or shear stresses. In this study, we present a novel device based on elastomeric materials that allowed us to stimulate NIH 3T3 fibroblasts through uniaxial strip stretching or shear fluid flow. Cell shape and structural response was observed using conventional approaches such as fluorescent microscopy. Cell orientation and actin cytoskeleton alignment along the direction of applied force were observed to occur after an initial 3 h time period for shear fluid flow and static uniaxial strip stretching experiments although these two directions of alignment were oriented orthogonal relative to each other. This response was then followed by an increasingly pronounced cell and actin cytoskeleton alignment parallel to the direction of force after 6, 12, and 24 h, with 85% of the cells aligned along the direction of force after 24 h. These results indicate that our novel device could be implemented to study the effects of multiple modes of mechanical stimulation on living cells while probing their structural response especially with respect to competing directions of alignment and orientation under these different modes of mechanical stimulation. We believe that this will be important in a diversity of fields including cell mechanotransduction, cell-material interactions, biophysics, and tissue engineering. PMID: 20033625 [PubMed - as supplied by publisher] |
| Insulin-producing cells derived from stem/progenitor cells: therapeutic implications for diabetes mellitus.
December 25, 2009 at 11:03 am
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| | Insulin-producing cells derived from stem/progenitor cells: therapeutic implications for diabetes mellitus. Med Mol Morphol. 2009 Dec;42(4):195-200 Authors: Hori Y One of the most common diseases of the pancreas is diabetes mellitus. The current treatment of exogenous insulin supply is not fully capable of achieving tight control of glucose regulation, leading to long-term complications. Hence, recent success in islet transplantation-based therapies for diabetes mellitus and the extreme shortage of pancreatic islets have motivated recent efforts to develop renewable sources of islet-replacement tissue. Of clinical interest, I review the recent progress on stem cell-based strategies for diabetes in view of regenerative medicine. PMID: 20033363 [PubMed - in process] |
| Biophysical mechanisms of single-cell interactions with microtopographical cues.
December 25, 2009 at 11:03 am
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| | Biophysical mechanisms of single-cell interactions with microtopographical cues. Biomed Microdevices. 2009 Dec 22; Authors: Patel AA, Thakar RG, Chown M, Ayala P, Desai TA, Kumar S Biophysical cues encoded in the extracellular matrix (ECM) are increasingly being explored to control cell behavior in tissue engineering applications. Recently, we showed that cell adhesion to microtopographical structures ("micropegs") can suppress proliferation in a manner that may be blunted by inhibiting cellular contractility, suggesting that this effect is related to altered cell-scaffold mechanotransduction. We now directly investigate this possibility at the microscale through a combination of live-cell imaging, single-cell mechanics methods, and analysis of gene expression. Using time-lapse imaging, we show that when cells break adhesive contacts with micropegs, they form F-actin-filled tethers that extend and then rupture at a maximum, critical length that is greater than trailing-edge tethers observed on topographically flat substrates. This critical tether length depends on myosin activation, with inhibition of Rho-associated kinase abolishing topography-dependent differences in tether length. Using cellular de-adhesion and atomic force microscopy indentation measurements, we show that the micropegs enhance cell-scaffold adhesive interactions without changing whole-cell elasticity. Moreover, micropeg adhesion increases expression of specific mechanotransductive genes, including RhoA GTPase and myosin heavy chain II, and, in myoblasts, the functional marker connexin 43. Together, our data support a model in which microtopographical cues alter the local mechanical microenvironment of cells by modulating adhesion and adhesion-dependent mechanotransductive signaling. PMID: 20033299 [PubMed - as supplied by publisher] |
| Delayed but excellent myogenic stem cell response of regenerating geriatric skeletal muscles in mice.
December 25, 2009 at 11:03 am
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| | Delayed but excellent myogenic stem cell response of regenerating geriatric skeletal muscles in mice. Biogerontology. 2009 Dec 24; Authors: Shavlakadze T, McGeachie J, Grounds MD The ability of very old animals to make new muscle after injury remains controversial. This issue has major implications for the regenerative potential of damaged geriatric human muscle, to age-related loss of muscle mass (sarcopenia) and to the proposed need for muscle stem cell therapy for the aged. To further address issues of inherent myogenic capacity and the role of host systemic factors in new muscle formation, whole muscle grafts were transplanted between geriatric (aged 27-29 months) and young (3 months) C57Bl/6J mice and compared with autografts in geriatric and young mice. Grafts were sampled at 5 and 10 days for histological analysis. Inflammation and formation of new myotubes was strikingly impaired at 5 days in the geriatric muscle autografts. However, there was a strong inflammatory response by the geriatric hosts to young muscle grafts and geriatric muscles provoked an inflammatory response by young hosts at 5 days. At 10 days, extensive myotube formation in geriatric muscle autografts (equivalent to that seen in young autografts and both other groups) confirmed excellent intrinsic capacity of myogenic (stem) cells to proliferate and fuse. The key conclusion is that a weaker chemotactic stimulus by damaged geriatric muscle, combined with a reduced inflammatory response of old hosts, results in delayed inflammation in geriatric muscle autografts. This delay is transient. Once inflammation occurs, myogenesis can proceed. The presence of well developed myotubes in old muscle autografts at 10 days confirms a very good inherent myogenic response of geriatric skeletal muscle. PMID: 20033288 [PubMed - as supplied by publisher] |
| Tissue engineering in endodontics.
December 25, 2009 at 11:03 am
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| | Tissue engineering in endodontics. J Oral Sci. 2009 Dec;51(4):495-507 Authors: Saber Sel-D Tissue engineering is the science of design and manufacture of new tissues to replace impaired or damaged ones. The key ingredients for tissue engineering are stem cells, the morphogens or growth factors that regulate their differentiation, and a scaffold of extracellular matrix that constitutes the microenvironment for their growth. Recently, there has been increasing interest in applying the concept of tissue engineering to endodontics. The aim of this study was to review the body of knowledge related to dental pulp stem cells, the most common growth factors, and the scaffolds used to control their differentiation, and a clinical technique for the management of immature non-vital teeth based on this novel concept. (J Oral Sci 51, 495-507, 2009). PMID: 20032600 [PubMed - in process] |
| Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation.
December 25, 2009 at 11:03 am
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| | Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood. 2009 Dec 23; Authors: Tarte K, Gaillard J, Lataillade JJ, Fouillard L, Becker M, Mossafa H, Tchirkov A, Rouard H, Henry C, Splingard M, Dulong J, Monnier D, Gourmelon P, Gorin NC, Sensebe L Clinical-grade human mesenchymal stromal cells (MSCs) have been expanded in vitro for tissue engineering or immunoregulatory purposes without standardized culture conditions or release criteria. Although human MSCs show poor susceptibility for oncogenic transformation, two recent studies described their capacity to accumulate chromosomal instability and to give rise to carcinoma in immunocompromised mice after long-term culture. We thus investigated the immunological and genetic features of MSCs expanded with fetal calf serum and fibroblast growth factor or with platelet lysate in 4 cell-therapy units during 2 multicenter clinical trials. Cultured MSCs showed a moderate expression of HLA-DR without alteration of their low immunogenicity or their immunomodulatory capacity. Moreover, some transient and donor-dependant recurring aneuploidy was detected in vitro, independently of the culture process. However, MSCs with or without chromosomal alterations showed progressive growth arrest and entered senescence without evidence of transformation either in vitro or in vivo. PMID: 20032501 [PubMed - as supplied by publisher] |
| Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration.
December 25, 2009 at 11:03 am
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| | Slug deficiency enhances self-renewal of hematopoietic stem cells during hematopoietic regeneration. Blood. 2009 Dec 23; Authors: Sun Y, Shao L, Bai H, Wang ZZ, Wu WS Both extrinsic and intrinsic mechanisms tightly govern HSC decisions of self-renewal and differentiation. However, transcription factors that can selectively regulate HSC self-renewal division after stress remain to be identified. Slug is an evolutionarily-conserved zinc-finger transcription factor that is highly expressed in primitive hematopoietic cells and is critical for the radioprotection of these key cells. We studied the effect of Slug in the regulation of HSCs in Slug-deficient mice under normal and stress conditions by using serial functional assays. Here, we show that Slug deficiency does not disturb hematopoiesis or alter HSC homeostasis and differentiation in bone marrow, but increases the numbers of primitive hematopoietic cells in the extramedullary spleen site. Deletion of Slug enhances HSC repopulating potential but not its homing and differentiation ability. Furthermore, Slug deficiency increases HSC proliferation and repopulating potential in vivo after myelosuppression and accelerates HSC expansion during in vitro culture. Therefore, we propose that Slug is essential for controlling the transition of HSCs from relative quiescence under steady-state condition to rapid proliferation under stress conditions. Our data suggest that inhibition of Slug in HSCs may present a novel strategy for accelerating hematopoietic recovery, thus providing therapeutic benefits for patients after clinical myelosuppressive treatment. PMID: 20032500 [PubMed - as supplied by publisher] |
| Engineering cardiac tissue in vivo from human adipose-derived stem cells.
December 25, 2009 at 11:03 am
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| | Engineering cardiac tissue in vivo from human adipose-derived stem cells. Biomaterials. 2009 Dec 21; Authors: Choi YS, Matsuda K, Dusting GJ, Morrison WA, Dilley RJ Cardiac tissue engineering offers promise as a surgical approach to cardiac repair, but requires an adequate source of cardiomyocytes. Here we evaluate the potential for generating human cardiac muscle cells in vivo from adipose-derived stem cells (ASC) by co-implanting in a vascularised tissue engineering chamber with inducing rat cardiomyocytes (rCM). Co-implantation (ASC-rCM) was compared with rCM or ASC controls alone after 6 weeks. Immunostaining using human nucleus specific antibody and cardiac markers revealed several fates for ASC in the chamber; (1) differentiation into cardiomyocytes and integration with co-implanted rCM; (2) differentiation into smooth muscle cells and recruitment into vascular structures; (3) adipogenic differentiation. ASC-rCM and ASC groups grew larger tissue constructs than rCM alone (212+/-25mul, 171+/-16mul vs. 137+/-15mul). ASC-rCM and rCM groups contracted spontaneously at up to 140bpm and generated a 10-15-fold larger volume of cardiac muscle (14.5+/-4.8mul and 18.5+/-2.6mul) than ASC alone group (1.3+/-0.5mul). Vascular volume in ASC-rCM group was twice that of the rCM group (28.7+/-5.0mul vs. 14.8+/-1.8mul). The cardiac tissue engineered by co-implanting human ASC with neonatal rCM showed in vivo plasticity of ASC and their cardiomyogenic potential in tissue engineering. ASC contribution to vascularisation also promoted the growth of engineered tissue, confirming their utility in this setting. PMID: 20031204 [PubMed - as supplied by publisher] |
| [Immunoregulatory function of mesenchymal stem cells and application of mesenchymal stem cells in therapy of autoimmune disease.]
December 25, 2009 at 11:03 am
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| | [Immunoregulatory function of mesenchymal stem cells and application of mesenchymal stem cells in therapy of autoimmune disease.] Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Dec;17(6):1605-8 Authors: Kong WX, Jiang XX, Mao N Mesenchymal stem cells (MSCs) are multipotent cells derived from many adult tissues, which can differentiate into cells of the mesodermal lineage, such as adipocyte, osteocyte and chondrocyte, as well as cells of other embryonic lineages. They are a promising tool for tissue engineering. In addition, MSC interacts with immune system, suppressing T cell, B cell and NK cell function and dendritic cell activities. MSC migrates to injured tissue to promote the survival of damaged cells and induces peripheral immune tolerance. The role of MSC in reducing the incidence and severity of graft versus host disease (GVHD) clinically has recently been reported. The immunoregulatory function of MSCs also shows a growing promise in the therapeutic application in autoimmune diseases. This review discusses the mechanism of MSC immunomodulatory ability and its therapeutic potential in autoimmune diseases. PMID: 20030957 [PubMed - in process] |
| Human Induced Pluripotent Stem Cells Produced Under Xeno-Free Conditions.
December 25, 2009 at 11:03 am
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| | Human Induced Pluripotent Stem Cells Produced Under Xeno-Free Conditions. Stem Cells Dev. 2009 Dec 23; Authors: Ross PJ, Suhr S, Rodriguez RM, Chang EA, Wang K, Siripattarapravat K, Ko T, Cibelli JB Induced Pluripotent Stem Cells (iPSCs) have radically advanced the field of regenerative medicine by making possible the production of patient specific pluripotent stem cells from adult individuals. While cell differentiation protocols are been successfully developed, and animal models of human disease have proved that these cells have the potential to treat human diseases and conditions produced as a consequence of aging, degeneration, injury and birth defects, logistical issues still remain unsolved and hamper the possibility of testing these cells in human clinical trials. Among them is the widely spread use of animal products for the generation and culture of iPSCs. We report here a xeno-free iPSC generation system that addresses all the steps of iPSCs production including the isolation and culture of adult skin fibroblasts, and iPSCs generation, expansion, and maintenance. iPSCs generated with a polycistronic lentiviral vector under xeno-free conditions displayed markers of pluripotency and gave rise to embryoid bodies displaying indicators of the three primary germ layers. Xeno-free IPSCs injected into nude mice produced classic teratomas, and teratoma explants cultured under conditions favoring fibroblastic cells gave rise to cells morphologically indistinguishable from input cells. Protocols here described will facilitate the implementation of new cellular therapies for pre-clinical and clinical studies, potentially reducing the regulatory burden without compromising the differentiation potential of the cells. PMID: 20030562 [PubMed - as supplied by publisher] |
| [Cell therapy for Parkinson disease]
December 25, 2009 at 11:03 am
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| | [Cell therapy for Parkinson disease] Rinsho Shinkeigaku. 2009 Nov;49(11):890-2 Authors: Muramatsu S Advances in the field of stem cell research have raised hopes of creating novel cell replacement therapies for Parkinson disease (PD), although double-blinded clinical trials have met with controversial success in patients implanted with fetal midbrain tissue and autopsy results have shown that some of the grafted fetal neurons displayed pathological changes typical of PD. Dopaminergic neurons have been efficiently derived from stem cells using various methods, and beneficial effects after transplantation have been demonstrated in animal models of PD. Some obstacles remain to be overcome before stem cell therapy can be routinely and safely used to treat PD in humans. A widely used prodrug/suicide gene therapy would be applied to stem cells to reduce risk of tumor formation. Since grafts were transplanted ectopically into the striatum instead of the substantia nigra in most current protocols, surviving dopaminergic neurons would not have to be the same subtype as the nigral cells. If the main mechanism underlying any functional recovery achieved by cell therapies is restoration of dopaminergic neurotransmission, then viral vector-mediated gene delivery of dopamine-synthesizing enzymes represents a more straightforward approach. Future targets for cell therapy should include some types of Parkinsonism with degeneration of striatal neurons. PMID: 20030240 [PubMed - in process] |
| [Future of stem cell therapy for neuronal regeneration]
December 25, 2009 at 11:03 am
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| | [Future of stem cell therapy for neuronal regeneration] Rinsho Shinkeigaku. 2009 Nov;49(11):834-6 Authors: Takahashi J Embryonic stem (ES) cells are expected as promising donor cells for cell transplantation therapy. For example, mouse or monkey ES cell-derived dopamine (DA) neurons can survive in the brain and relieve Parkinson's disease (PD) symptoms in rat or monkey models. In 2001 and 2003, the results of a double-blind trial of the transplantation of human embryonic DA neurons into patients with PD were reported. These results teach us two things. First, cell transplantation has been clinically proven to be effective as a treatment for PD, although the effects are still far from optimal. Second, several problems remain to be solved, including patient selection, optimal donor cell volume, targeting of injection, immunosuppression, and control of dyskinesia. DA neurons have also been generated from several human ES cell lines. Furthermore, functional recovery of rat PD models after transplantation was observed. One of the major problems in ES cell transplantation is tumor formation, which is caused by a small fraction of undifferentiated ES cells in the graft. So, it is essential for undifferentiated ES cells to be eliminated from the graft for clinical application. These efforts will lead to clinical application of ES cell transplantation to the patients with PD. PMID: 20030224 [PubMed - in process] |
| Clinical implication of endothelial progenitor cells.
December 25, 2009 at 11:03 am
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| | Clinical implication of endothelial progenitor cells. Expert Rev Mol Diagn. 2010 Jan;10(1):89-105 Authors: Foresta C, De Toni L, Ferlin A, Di Mambro A The exact origin and functional definition of endothelial progenitor cells (EPCs) remains rather controversial, but many authors agree that the main feature of EPCs is the ability to directly participate in vessel growth by differentiation into endothelial cells in vivo. The majority of these cells originate from the hematopoietic stem cells of the bone marrow and, under specific signals, differentiate and shift into the systemic circulation, contributing to the neoangiogenic process and repair of the damaged endothelial monolayer. Recently, it has been demonstrated that the number and function of EPCs is positively linked with an improved endothelial function or regeneration but inversely correlated with cardiovascular risk factors: a reduced number of EPCs is an independent predictor of morbidity and mortality of cardiovascular diseases and of atherosclerotic disease progression. Owing to their role in endogenous maintenance and repair of damaged endothelium, EPCs have been examined for therapeutic potential in ischemic diseases and there are evidence-based perspectives regarding their use for vascular regenerative medicine. PMID: 20030028 [PubMed - in process] |
| Discussion. Long-term persistence of tissue-engineered adipose flaps in a murine model to 1 year: an update.
December 25, 2009 at 11:03 am
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| | Discussion. Long-term persistence of tissue-engineered adipose flaps in a murine model to 1 year: an update. Plast Reconstr Surg. 2009 Oct;124(4):1085-6 Authors: Pu LL PMID: 19935291 [PubMed - indexed for MEDLINE] |
| Expansion and differentiation of neural progenitors derived from the human adult enteric nervous system.
December 25, 2009 at 11:03 am
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| | Expansion and differentiation of neural progenitors derived from the human adult enteric nervous system. Gastroenterology. 2009 Dec;137(6):2063-2073.e4 Authors: Metzger M, Bareiss PM, Danker T, Wagner S, Hennenlotter J, Guenther E, Obermayr F, Stenzl A, Koenigsrainer A, Skutella T, Just L BACKGROUND & AIMS: Neural stem and progenitor cells from the enteric nervous system have been proposed for use in cell-based therapies against specific neurogastrointestinal disorders. Recently, enteric neural progenitors were generated from human neonatal and early postnatal (until 5 years after birth) gastrointestinal tract tissues. We investigated the proliferation and differentiation of enteric nervous system progenitors isolated from human adult gastrointestinal tract. METHODS: Human enteric spheroids were generated from adult small and large intestine tissues and then expanded and differentiated, depending on the applied cell culture conditions. For implantation studies, spheres were grafted into fetal slice cultures and embryonic aganglionic hindgut explants from mice. Differentiating enteric neural progenitors were characterized by 5-bromo-2-deoxyuridine labeling, in situ hybridization, immunocytochemistry, quantitative real-time polymerase chain reaction, and electrophysiological studies. RESULTS: The yield of human neurosphere-like bodies was increased by culture in conditional medium derived from fetal mouse enteric progenitors. We were able to generate proliferating enterospheres from adult human small or large intestine tissues; these enterospheres could be subcultured and maintained for several weeks in vitro. Spheroid-derived cells could be differentiated into a variety of neuronal subtypes and glial cells with characteristics of the enteric nervous system. Experiments involving implantation into organotypic intestinal cultures showed the differentiation capacity of neural progenitors in a 3-dimensional environment. CONCLUSIONS: It is feasible to isolate and expand enteric progenitor cells from human adult tissue. These findings offer new strategies for enteric stem cell research and future cell-based therapies. PMID: 19549531 [PubMed - indexed for MEDLINE] | | | 
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