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‣ Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

Lobba, A. R. M.; Forni, M. F.; Carreira, A. C. O.; Sogayar, Mari Cleide
Fonte: WILEY-BLACKWELL; HOBOKEN Publicador: WILEY-BLACKWELL; HOBOKEN
Tipo: Artigo de Revista Científica
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The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis on the basis for tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized and relatively rare cell population, which is responsible for tumor initiation, self-renewal, and maintenance, in addition to accumulation of mutation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different genetic markers have been used to isolate breast CSCs, none of which have been correlated with the tumorigenicity or metastatic potential of the cells, limiting their precise characterization and clinical application in the development of therapeutic protocols. Here, we sought for subpopulations of CSCs by analyzing 10 judiciously chosen stem cell markers in a normal breast cell line (MCF10-A) and in four human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and Hs578-T) displaying different degrees of metastatic and invasiveness potential. We were able to identify two markers, which are differentially expressed in nontumorigenic versus tumor cells. The CD90 marker was highly expressed in the malignant cell lines. Interestingly, the CD14 molecule displayed higher expression levels in the nontumorigenic cell line. Therefore...

‣ What do we know about the neurogenic potential of different stem cell types?

Lepski,Guilherme
Fonte: Academia Brasileira de Neurologia - ABNEURO Publicador: Academia Brasileira de Neurologia - ABNEURO
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/07/2012 Português
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Cell therapies, based on transplantation of immature cells, are being considered as a promising tool in the treatment of neurological disorders. Many efforts are being concentrated on the development of safe and effective stem cell lines. Nevertheless, the neurogenic potential of some cell lines, i.e., the ability to generate mature neurons either in vitro or in vivo, is largely unknown. Recent evidence indicate that this potential might be distinct among different cell lines, therefore limiting their broad use as replacement cells in the central nervous system. Here, we have reviewed the latest advancements regarding the electrophysiological maturation of stem cells, focusing our attention on fetal-derived-, embryonic-, and induced pluripotent stem cells. In summary, a large body of evidence supports the biological safety, high neurogenic potential, and in some diseases probable clinical efficiency related to fetal-derived cells. By contrast, reliable data regarding embryonic and induced pluripotent stem cells are still missing.

‣ Establishment of new murine embryonic stem cell lines for the generation of mouse models of human genetic diseases

Sukoyan,M.A.; Kerkis,A.Y.; Mello,M.R.B.; Kerkis,I.E.; Visintin,J.A.; Pereira,L.V.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/05/2002 Português
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Embryonic stem cells are totipotent cells derived from the inner cell mass of blastocysts. Recently, the development of appropriate culture conditions for the differentiation of these cells into specific cell types has permitted their use as potential therapeutic agents for several diseases. In addition, manipulation of their genome in vitro allows the creation of animal models of human genetic diseases and for the study of gene function in vivo. We report the establishment of new lines of murine embryonic stem cells from preimplantation stage embryos of 129/Sv mice. Most of these cells had a normal karyotype and an XY sex chromosome composition. The pluripotent properties of the cell lines obtained were analyzed on the basis of their alkaline phosphatase activity and their capacity to form complex embryoid bodies with rhythmically contracting cardiomyocytes. Two lines, USP-1 and USP-3, with the best in vitro characteristics of pluripotency were used in chimera-generating experiments. The capacity to contribute to the germ line was demonstrated by the USP-1 cell line. This cell line is currently being used to generate mouse models of human diseases.

‣ Bipotential mouse embryonic liver stem cell lines contribute to liver regeneration and differentiate as bile ducts and hepatocytes

Strick-Marchand, Hélène; Morosan, Serban; Charneau, Pierre; Kremsdorf, Dina; Weiss, Mary C.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
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Cell lines have many advantages: they can be manipulated genetically, expanded, and stockpiled for organ transplantation. Freshly isolated hepatocytes, oval cells, pancreatic cells, and hematopoietic stem cells have been shown to repopulate the damaged liver. Here we show that bipotential mouse embryonic liver (BMEL) stem cell lines participate in liver regeneration in albumin–urokinase plasminogen activator/severe combined immunodeficiency disease (Alb-uPA/SCID) transgenic mice. In the liver, BMEL-GFP cells proliferate and differentiate into both hepatocytes and bile ducts, forming small to large clusters detected throughout the 3–8 weeks analyzed after transplantation. Moreover, they respond like host cells to signals for growth, differentiation, and even zonal expression of metabolic enzymes, showing regulated expression of cytokeratins and liver-enriched transcription factors. Immunostaining for MHC class I molecules revealed that cells do not coexpress donor and recipient H-2 haplotypes, as would be the case had cell fusion occurred. This report shows that immortalized stem cell lines not only are competent to participate in the repair of a damaged tissue but also can differentiate into the two major epithelial cell types of a complex organ...

‣ Immune-privileged embryonic Swiss mouse STO and STO cell-derived progenitor cells: major histocompatibility complex and cell differentiation antigen expression patterns resemble those of human embryonic stem cell lines

Koch, Katherine S; Son, Kyung-Hwa; Maehr, Rene; Pellicciotta, Illenia; Ploegh, Hidde L; Zanetti, Maurizio; Sell, Stewart; Leffert, Hyam L
Fonte: Blackwell Publishing Ltd Publicador: Blackwell Publishing Ltd
Tipo: Artigo de Revista Científica
Publicado em 01/09/2006 Português
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Embryonic mouse STO (S, SIM; T, 6-thioguanine resistant; O, ouabain resistant) and 3(8)21-enhanced green fluorescent protein (EGFP) cell lines exhibit long-term survival and hepatic progenitor cell behaviour after xenogeneic engraftment in non-immunosuppressed inbred rats, and were previously designated major histocompatibility complex (MHC) class I- and class II-negative lines. To determine the molecular basis for undetectable MHC determinants, the expression and haplotype of H-2K, H-2D, H-2L and I-A proteins were reassessed by reverse transcriptase–polymerase chain reaction (RT-PCR), cDNA sequencing, RNA hybridization, immunoblotting, quantitative RT-PCR (QPCR), immunocytochemistry and flow cytometry. To detect cell differentiation (CD) surface antigens characteristic of stem cells, apoptotic regulation or adaptive immunity that might facilitate progenitor cell status or immune privilege, flow cytometry was also used to screen untreated and cytokine [interferon (IFN)-γ]-treated cultures. Despite prior PCR genotyping analyses suggestive of H-2q haplotypes in STO, 3(8)21-EGFP and parental 3(8)21 cells, all three lines expressed H-2K cDNA sequences identical to those of d-haplotype BALB/c mice, as well as constitutive and cytokine-inducible H-2Kd determinants. In contrast...

‣ Gene-specific vulnerability to imprinting variability in human embryonic stem cell lines

Kim, Kee-Pyo; Thurston, Alexandra; Mummery, Christine; Ward-van Oostwaard, Dorien; Priddle, Helen; Allegrucci, Cinzia; Denning, Chris; Young, Lorraine
Fonte: Cold Spring Harbor Laboratory Press Publicador: Cold Spring Harbor Laboratory Press
Tipo: Artigo de Revista Científica
Publicado em /12/2007 Português
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Disregulation of imprinted genes can be associated with tumorigenesis and altered cell differentiation capacity and so could provide adverse outcomes for stem cell applications. Although the maintenance of mouse and primate embryonic stem cells in a pluripotent state has been reported to disrupt the monoallelic expression of several imprinted genes, available data have suggested relatively higher imprint stability in the human equivalents. Identification of 202 heterozygous loci allowed us to examine the allelic expression of 22 imprinted genes in 22 human embryonic stem cell lines. Half of the genes examined (IPW, H19, MEG3, MEST isoforms 1 and 2, PEG10, MESTIT1, NESP55, ATP10A, PHLDA2, IGF2) showed variable allelic expression between lines, indicating vulnerability to disrupted imprinting. However, seven genes showed consistent monoallelic expression (NDN, MAGEL2, SNRPN, PEG3, KCNQ1, KCNQ1OT1, CDKN1C). Furthermore, four genes known to be monoallelic or to exhibit polymorphic imprinting in later-developing human tissues (TP73, IGF2R, WT1, SLC22A18) were always biallelic in hESCs. MEST isoform 1, PEG10, and NESP55 showed an association between the variability observed in interline allelic expression status and the DNA methylation of previously identified regulatory regions. Our results demonstrate gene-specific differences in the stability of imprinted loci in human embryonic stem cells and identify disrupted DNA methylation as one potential mechanism. We conclude the prudence of including comprehensive imprinting analysis in the continued characterization of human embryonic stem cell lines.

‣ Chromosome number variation in three mouse embryonic stem cell lines during culture

Rebuzzini, Paola; Neri, Tui; Zuccotti, Maurizio; Redi, Carlo Alberto; Garagna, Silvia
Fonte: Springer Netherlands Publicador: Springer Netherlands
Tipo: Artigo de Revista Científica
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Although mouse embryonic stem cell lines (mESCs) have been established since 1981, systematic studies about chromosomal changes during culture are lacking. In this study, we report the results of a cytogenetic analysis performed on three mESC lines (named UPV02, UPV06 and UPV08) cultured for a period of 3 months. At time intervals, the variation of the chromosome number together with the expression of markers of the undifferentiated status, i.e., OCT-4, SSEA-1, FOM-1 and alkaline phosphatase activity, were determined. The three mESC lines showed a progressive loss of euploid metaphases during the 3 months period of culture. Chromosome abnormalities were accumulated at the latest passages analysed. Metacentric chromosomes were the most frequent chromosome abnormality observed throughout the period of culture. Interestingly, in coincidence with, or few passages after, the drop of euploidy, the alkaline phosphatase activity was partially or totally lost, whereas the OCT-4, SSEA-1 and FOM-1 stem markers were always positive throughout the period of culture. Our results remark the necessity to perform the karyotype analysis during culture in order to develop new culture conditions to maintain the correct chromosome complement in long-term culture of mESC lines.

‣ Regulatory networks define phenotypic classes of human stem cell lines

Müller, Franz-Josef; Laurent, Louise C.; Kostka, Dennis; Ulitsky, Igor; Williams, Roy; Lu, Christina; Park, In-Hyun; Rao, Mahendra S.; Shamir, Ron; Schwartz, Philip H.; Schmidt, Nils O.; Loring, Jeanne F.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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Stem cells are defined as self-renewing cell populations that can differentiate into multiple distinct cell types. However, hundreds of different human cell lines from embryonic, fetal, and adult sources have been called stem cells, even though they range from pluripotent cells, typified by embryonic stem cells, which are capable of virtually unlimited proliferation and differentiation, to adult stem cell lines, which can generate a far more limited repertory of differentiated cell types. The rapid increase in reports of new sources of stem cells and their anticipated value to regenerative medicine1, 2 have highlighted the need for a general, reproducible method for classification of these cells3. We report here the creation and analysis of a database of global gene expression profiles (“Stem Cell Matrix”) that enables the classification of cultured human stem cells in the context of a wide variety of pluripotent, multipotent, and differentiated cell types. Using an unsupervised clustering method4, 5 to categorize a collection of ~150 cell samples, we discovered that pluripotent stem cell lines group together, while other cell types, including brain-derived neural stem cell lines, are very diverse. Using further bioinformatic analysis6 we uncovered a protein-protein network (“PluriNet”) that is shared by the pluripotent cells (embryonic stem cells...

‣ Generation of Induced Pluripotent Stem Cell Lines from Tibetan Miniature Pig*

Esteban, Miguel A.; Xu, Jianyong; Yang, Jiayin; Peng, Meixiu; Qin, Dajiang; Li, Wen; Jiang, Zhuoxin; Chen, Jiekai; Deng, Kang; Zhong, Mei; Cai, Jinglei; Lai, Liangxue; Pei, Duanqing
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
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Induced pluripotent stem cell (iPS) technology appears to be a general strategy to generate pluripotent stem cells from any given mammalian species. So far, iPS cells have been reported for mouse, human, rat, and monkey. These four species have also established embryonic stem cell (ESC) lines that serve as the gold standard for pluripotency comparisons. Attempts have been made to generate porcine ESC by various means without success. Here we report the successful generation of pluripotent stem cells from fibroblasts isolated from the Tibetan miniature pig using a modified iPS protocol. The resulting iPS cell lines more closely resemble human ESC than cells from other species, have normal karyotype, stain positive for alkaline phosphatase, express high levels of ESC-like markers (Nanog, Rex1, Lin28, and SSEA4), and can differentiate into teratomas composed of the three germ layers. Because porcine physiology closely resembles human, the iPS cells reported here provide an attractive model to study certain human diseases or assess therapeutic applications of iPS in a large animal model.

‣ Derivation of 30 human embryonic stem cell lines—improving the quality

Ström, Susanne; Holm, Frida; Bergström, Rosita; Strömberg, Anne-Marie; Hovatta, Outi
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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We have derived 30 human embryonic stem cell lines from supernumerary blastocysts in our laboratory. During the derivation process, we have studied new and safe method to establish good quality lines. All our human embryonic stem cell lines have been derived using human foreskin fibroblasts as feeder cells. The 26 more recent lines were derived in a medium containing serum replacement instead of fetal calf serum. Mechanical isolation of the inner cell mass using flexible metal needles was used in deriving the 10 latest lines. The lines are karyotypically normal, but culture adaptation in two lines has been observed. Our human embryonic stem cell lines are banked, and they are available for researchers.

‣ Analysis of long-term culture properties and pluripotent character of two sibling human embryonic stem cell lines derived from discarded embryos

Venu, Parvathy; Chakraborty, Sanjukta; Inamdar, Maneesha S.
Fonte: Springer-Verlag Publicador: Springer-Verlag
Tipo: Artigo de Revista Científica
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We had earlier reported the derivation and characterization of two new sibling human embryonic stem cell lines BJNhem19 and BJNhem20, from discarded grade III embryos of Indian origin. We report here the characteristics of the two sibling cell lines after long-term continuous culture for over 2 yr during which they have been passaged over 200 times. We show that both cell lines adapt well to culture on various mouse and human feeders as well as in feeder-free conditions. The cells show normal diploid karyotype and continue to express all pluripotency markers. Both cell lines differentiate to derivatives of all three germ layers in vitro. However as reported earlier, BJNhem19 is unable to generate teratomas in nude or SCID mice or differentiate to beating cardiomyocytes when tested over several passages during long-term stable culture. On the other hand, the cardiac differentiation capacity of BJNhem20 is greatly increased, and it can generate beating cardiomyocytes that proliferate when isolated and cultured further. In conclusion, the two cell lines have maintained a stable phenotype for over 2 yr and are indeed immortal. Their derivation from grade III embryos does not seem to have any adverse effect on their long-term phenotype. The cells can be obtained for research purposes from the UK Stem Cell Bank and from the authors.

‣ PI3 K/Akt/mTOR-Mediated Translational Control Regulates Proliferation and Differentiation of Lineage-Restricted RoSH Stem Cell Lines

Que, Jianwen; Lian, Qizhou; El Oakley, Reida M; Lim, Sai-Kiang; Lim, Bing
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
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Background: We have previously derived highly similar lineage-restricted stem cell lines, RoSH and E-RoSH cell lines from mouse embryos and CD9hi SSEA-1- differentiated mouse embryonic stem cells, respectively. These cell lines are not pluripotent and differentiate readily into endothelial cells in vitro and in vivo. Results: We investigated the signaling pathway that maintains proliferation of these cells in an undifferentiated state, and demonstrate that PI3 K/Akt/mTOR, but not Raf/MEK/Erk, signaling in these cells was active during proliferation and was downregulated during endothelial differentiation. Inhibition of PI3 K/Akt/mTOR signaling, but not Raf/MEK/Erk, reduced proliferation and induced expression of endothelial specific proteins. During differentiation or inhibition of PI3 K/Akt/mTOR signaling, cyclinD2 transcript abundance in ribosome-enriched RNA but not in total RNA was reduced with a corresponding reduction in protein level. In contrast, transcript abundance of endothelial-specific genes e.g. Kdr, Tek and Pdgfrα in ribosome-enriched RNA fraction was not reduced and their protein levels were increased. Together these observations suggested that translational control mediated by PI3K/Akt/mTOR signaling was critical in regulating proliferation and endothelial differentiation of lineage-restricted RoSH-like stem cell lines. Conclusion: This study highlights translation regulation as a critical regulatory mechanism during proliferation and differentiation in stem cells.

‣ Ovarian Cancer Spheroid Cells with Stem Cell-Like Properties Contribute to Tumor Generation, Metastasis and Chemotherapy Resistance through Hypoxia-Resistant Metabolism

Liao, Jianqun; Qian, Feng; Tchabo, Nana; Mhawech-Fauceglia, Paulette; Beck, Amy; Qian, Zikun; Wang, Xinhui; Huss, Wendy J.; Lele, Shashikant B.; Morrison, Carl D.; Odunsi, Kunle
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
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Cells with sphere forming capacity, spheroid cells, are present in the malignant ascites of patients with epithelial ovarian cancer (EOC) and represent a significant impediment to efficacious treatment due to their putative role in progression, metastasis and chemotherapy resistance. The exact mechanisms that underlie EOC metastasis and drug resistance are not clear. Understanding the biology of sphere forming cells may contribute to the identification of novel therapeutic opportunities for metastatic EOC. Here we generated spheroid cells from human ovarian cancer cell lines and primary ovarian cancer. Xenoengraftment of as few as 2000 dissociated spheroid cells into immune-deficient mice allowed full recapitulation of the original tumor, whereas >105 parent tumor cells remained non-tumorigenic. The spheroid cells were found to be enriched for cells with cancer stem cell-like characteristics such as upregulation of stem cell genes, self-renewal, high proliferative and differentiation potential, and high aldehyde dehydrogenase (ALDH) activity. Furthermore, spheroid cells were more aggressive in growth, migration, invasion, scratch recovery, clonogenic survival, anchorage-independent growth, and more resistant to chemotherapy in vitro. 13C-glucose metabolic studies revealed that spheroid cells route glucose predominantly to anaerobic glycolysis and pentose cycle to the detriment of re-routing glucose for anabolic purposes. These metabolic properties of sphere forming cells appear to confer increased resistance to apoptosis and contribute to more aggressive tumor growth. Collectively...

‣ Dissecting Molecular Similarities and Differences Between Pluripotent Stem Cell Lines

Choi, Jiho
Fonte: Harvard University Publicador: Harvard University
Tipo: Thesis or Dissertation; text Formato: application/pdf
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Traditionally, pluripotent stem cells are derived from preimplantation embryos and fetal germ cells, which give rise to embryonic stem cells (ESCs) and embryonic germ cells (EGCs), respectively, In contrast, induced pluripotent stem cells (iPSCs) are derived from somatic cells upon overexpression of defined transcription factors such as Oct4, Sox2, Klf4 and c-Myc. Despite their origin from different cell types, all of these pluripotent stem cell lines share the ability to self-renew indefinitely in culture while retaining the capacity to differentiate into derivatives of all three germ layers. Because pluripotent cells provide a useful tool in basic research and cell therapy, it is critical to understand the molecular similarities and differences between ESCs, EGCs and iPSCs. The studies presented in this thesis aim to address the equivalence of different pluripotent cell types. In the first study, we performed a systematic comparison of DNA methylation and gene expression patterns between isogenic mouse ESCs and EGCs. Surprisingly, we found that global DNA methylation patterns were indistinguishable between ESC and EGC lines of the same sex, while female cell lines exhibited global hypomethylation compared to male cell lines. Mechanistically...

‣ Establishment and characterization of several liver cell lines as tools for the study of physio-pathological cellular interplay

COSTA, VIVIANA
Fonte: La Sapienza Universidade de Roma Publicador: La Sapienza Universidade de Roma
Tipo: Tese de Doutorado
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Establishment and characterization of cell lines as tools for the study of physio-pathological liver cellular interplay The liver is the largest internal organ of the body, constituting approximately 2% to 5% of body weight in the adult and 5% in the neonate. This organ plays a central role in metabolic homeostasis and it is responsible for the synthesis, storage and redistribution of nutrients, carbohydrates, fats and vitamins. The liver has a peculiar and fascinating ability: it is able to regenerate itself after loss of parenchyma for surgical resection or injury caused by drugs, toxins or acute viral disease. Considering the variety of liver functions, it is not surprising that a large number of cell types and cell–cell interactions are required for its functionality. Most of the liver functions are carried out by the hepatocytes (about 70-75% of hepatic cells); these, together with cholangiocytes (10-5 %), both of endodermal derivation, constitute the hepatic parenchyma. The other 20% made up of non-parenchymal cells, includes: 1) Kupffer cells, essential for the phagocytosis of foreign particles as well as for the cytokines production, 2) stellate cells, that store vitamin A and produce extra-cellular matrix (ECM) components...

‣ Induced pluripotent stem cell lines derived from human gingival fibroblasts and periodontal ligament fibroblasts

Wada, N.; Wang, B.; Lin, N.H.; Laslett, A.; Gronthos, S.; Bartold, P.
Fonte: Blackwell Munksgaard Publicador: Blackwell Munksgaard
Tipo: Artigo de Revista Científica
Publicado em //2011 Português
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Background and Objective: Human induced pluripotent stem (iPS) cells, which have similar properties to human embryonic stem (hES) cells, have been generated from neonatal and adult human dermal fibroblasts by reprogramming. iPS cells have high pluripotency and differentiation potential, and may be a potential autologous stem cell source for future regenerative therapy. Material and Methods: iPS cell lines from human gingival fibroblasts and, for the first time, from periodontal ligament fibroblasts, were generated by reprogramming using a retroviral transduction cocktail of OCT3/4, SOX2, KLF4 and c-MYC. iPS induction was investigated through expression of the embryonic stem cell markers SSEA4, OCT4, NANOG, GCTM-2, TG30 and TRA-1-60. Following in vitro differentiation, the expression of genes for differentiation markers for ectoderm (SOX1, PAX6), mesoderm [RUNX1, T(Brachyury)] and endoderm (GATA4, AFP) was assessed by real-time RT-PCR. The ability to form teratomas following implantation into mouse testes was assessed by histology. Results: Human gingival fibroblast- and periodontal ligament fibroblast-derived iPS cells showed similar characteristics to hES cells. Both sets of iPS cells displayed colony morphology comparable to that of hES cells and expressed the hES cell-associated cell-surface antigens...

‣ Untersuchungen zur antikörper-abhängigen zellvermittelten antileukämischen Aktivität (ADCC) bei Kindern nach allogener Stammzelltransplantation; Investigations of antibody dependent cellular mediated cytotoxicity in children after allogenic stem cell transplantation

Stanojevic, Stanoje
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
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Die Haupttodesursache nach allogener Stammzelltransplantation stellt das Rezidiv dar. Ursache hierfür ist das Persistieren von residuellen Leukämiezellen im Knochenmark, der sogenannten "Minimal Residual Disease" (MRD). Ziel immuntherapeutischer Ansätze ist es, derartige "Minimal Residual Disease"-Zellen nach allogener Stammzelltransplantation spezifisch zu eliminieren. Eine Möglichkeit um dieses Ziel zu erreichen, ist die Ausnutzung der antikörper-abhängigen zellvermittelten Zytotoxizität (ADCC). Im Rahmen der vorliegenden Dissertation wurde untersucht, ob Kinder, die allogen mit positiv-angereicherten CD34-positiven Stammzellen transplantiert worden sind, zur Ausübung der ADCC fähig sind. Dazu wurden mononukleäre Zellen aus dem peripheren Blut (PBMNC) allogen transplantierter Kinder isoliert und deren zytotoxische Fähigkeit beziehungsweise ADCC in vitro mittels des BATDA-Release-Assays überprüft. Für die ADCC wurde ein gegen das CD20 Antigen gerichteter chimärer Antikörper (Rituximab) verwendet. Außerdem wurde versucht, die ADCC mittels Interleukin-2 Stimulation (IL-2) zu steigern. In vitro konnte in der vorliegenden Arbeit gezeigt werden, daß 12 von 18 untersuchten Patienten (67 Prozent) in der Lage waren, ohne Interleukin-2 Aktivierung eine ADCC gegen die Tumorzellinien Raji oder MHH-CALL-4 auszuüben. Darüber hinaus wurden dann 94 Prozent der selben untersuchten Patienten durch Stimulation mit Interleukin-2 in die Lage versetzt...

‣ Generation of functional mesenchymal stem cells from different induced pluripotent stem cell lines

Hynes, K.; Menicanin, D.; Mrozik, K.; Gronthos, S.; Bartold, P.M.
Fonte: Mary Ann Liebert Publicador: Mary Ann Liebert
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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The therapeutic potential of mesenchymal stem cells (MSC) has highlighted the need for identifying easily accessible and reliable sources of these cells. An alternative source for obtaining large populations of MSC is through the controlled differentiation of induced pluripotent stem cells (iPSC). In the present study, colonies of iPSC were cultured in MSC culture media for 2 weeks. Serial passaging then selected for fast growing MSC-like cells with a typical fibroblastic morphology and the capacity to proliferate on standard culture flasks without feeder cells. MSC-like cells were developed from iPSC lines arising from three different somatic tissues: gingiva, periodontal ligament (PDL), and lung. The iPSC-MSC like cells expressed key MSC-associated markers (CD73, CD90, CD105, CD146, and CD166) and lacked expression of pluripotent markers (TRA160, TRA181, and alkaline phosphatase) and hematopoietic markers (CD14, CD34, and CD45). In vitro iPSC-MSC-like cells displayed the capacity to differentiate into osteoblasts, adipocytes, and chondrocytes. In vivo subcutaneous implantation of the iPSC-MSC-like cells into NOD/SCID mice demonstrated that only the PDL-derived iPSC-MSC-like cells exhibited the capacity to form mature mineralized structures which were histologically similar to mature bone. These findings demonstrate that controlled induction of iPSC into fibroblastic-like cells that phenotypically and functionally resemble adult MSC is an attractive approach to obtain a readily available source of progenitor cells for orthopedic and dental-related tissue-engineering applications. However...

‣ Culture Condition Difference for Establishment of New Embryonic Stem Cell Lines from the C57BL/6 and BALB/c Mouse Strains

Baharvand, Hossein; Matthaei, Klaus
Fonte: Society for In Vitro Biology Publicador: Society for In Vitro Biology
Tipo: Artigo de Revista Científica
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Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. These cells are appropriate for creation of animal models of human genetic diseases, the study of gene function in vivo and differentiation into specific types as potential therapeutic agents for several human diseases. We describe here, the production of new ES cell lines from blastocysts recovered from the C57BL/6 and BALB/c mouse strains by changing the concentration of leukemia inhibitory factor (LIF) and primary culture conditions. The established cell lines were analyzed by simple karyotype, C banding, alkaline phosphatase activity, and Oct-4 expression as well as for the presence of the SRY gene. Two ES cell lines from C57BL/6 and three from the BALB/c were produced. The two C57BL/6 ES cell lines were established with either 1000 or 5000 IU LIF, whereas the BALB/c ES cell lines required 5000 IU LIF. Four of the ES cell lines had a normal karyotype. C banding and sex-determining region of Y chromosome-polymerase chain reaction showed that all cell lines had an XY sex chromosome composition. All five of the cell lines expressed alkaline phosphatase activity and Oct-4. One of the BALB/c ES cell lines, when injected into C57BL/6 blastocysts...

‣ The Attack of the Clones: Patent Law and Stem Cell Research

Rimmer, Matthew
Fonte: The Law Book Company Publicador: The Law Book Company
Tipo: Artigo de Revista Científica
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This article considers the integral role played by patent law in respect of stem cell research. It highlights concerns about commercialization, access to essential medicines and bioethics. The article maintains that there is a fundamental ambiguity in the Patents Act 1990 (Cth) as to whether stem cell research is patentable subject matter. There is a need to revise the legislation in light of the establishment of the National Stem Cell Centre and the passing of the Research Involving Embryos Act 2002 (Cth). The article raises concerns about the strong patent protection secured by the Wisconsin Alumni Research Foundation and Geron Corporation in respect of stem cell research in the United States. It contends that a number of legal reforms could safeguard access to stem cell lines, and resulting drugs and therapies. Finally, this article explores how ethical concerns are addressed within the framework of the European Biotechnology Directive. It examines the decision of the European Patent Office in relation to the so-called "Edinburgh patent", and the inquiry of the European Group on Ethics in Science and New Technologies into "The Ethical Aspects of Patenting Involving Human Stem Cells".