2024-03-28T10:14:58Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/1964952019-08-30T11:28:23Zcom_10033_196529com_10033_56876col_10033_196534
Iacob, Razvan
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Rüdrich, Urda
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Rothe, Michael
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500
Kirsch, Sarah
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500
Maasoumy, Benjamin
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500
Narain, Nidhi
c10a9c487ab5ea43b0f450924e48b697
500
Verfaillie, Catherine M
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Sancho-Bru, Pau
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Iken, Marcus
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Popescu, Irinel
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Schambach, Axel
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Manns, Michael P
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Bock, Michael
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Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
2011-12-08T14:51:44Z
2011-12-08T14:51:44Z
2011-05
Induction of a mature hepatocyte phenotype in adult liver derived progenitor cells by ectopic expression of transcription factors. 2011, 6 (3):251-61 Stem Cell Res
1876-7753
21474405
10.1016/j.scr.2011.02.002
http://hdl.handle.net/10033/196495
Stem cell research
By ectopic expression of a distinct combination of transcription factors we aimed to induce a mature hepatocyte phenotype in an adult liver derived progenitor cell population (ALDPC).
en
Adult Stem Cells
Animals
Cell Differentiation
Cells, Cultured
Gene Expression
Hepatocytes
Liver
Mice
Mice, Inbred C57BL
Transcription Factors
Induction of a mature hepatocyte phenotype in adult liver derived progenitor cells by ectopic expression of transcription factors.
Article
2018-06-12T22:36:46Z
By ectopic expression of a distinct combination of transcription factors we aimed to induce a mature hepatocyte phenotype in an adult liver derived progenitor cell population (ALDPC).
ORIGINAL
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10033/196495
oai:hzi.openrepository.com:10033/196495
2019-08-30 11:28:23.905
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2094892019-08-30T11:32:17Zcom_10033_196529com_10033_56876col_10033_196534
Wu, Guangming
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500
Liu, Na
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500
Rittelmeyer, Ina
5591739dffacbaaa0b16ce981a891795
500
Sharma, Amar Deep
dc76f27bfc5bc009287ea10740e6d672
500
Sgodda, Malte
b7e6a0e408730a18fcda4f3bfd541c13
500
Zaehres, Holm
dc1d6b379b599755007a177c8608ac02
500
Bleidissel, Martina
18e544a1a1cb074de3a7a7a5f8c59259
500
Greber, Boris
a3245201ade2880b492f7d67b5d5930d
500
Gentile, Luca
2485123b9f47f28ea7c40f5138332a26
500
Han, Dong Wook
35da995c04dc34f38a8343bfdfb7c777
500
Rudolph, Cornelia
20eb9103d3f3ee91c9ab4a092057cfb0
500
Steinemann, Doris
a5bb5f70b0b07d34c7f8cc59b658b7a8
500
Schambach, Axel
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500
Ott, Michael
6b1ad6193d116de643e4166e6ecab12b
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Schöler, Hans R
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Cantz, Tobias
cb862a94e1531235b5a956fc0847fdf5
500
Max-Planck-Institute for Molecular Biomedicine, Münster, Germany.
2012-02-06T15:29:28Z
2012-02-06T15:29:28Z
2011-07
Generation of healthy mice from gene-corrected disease-specific induced pluripotent stem cells. 2011, 9 (7):e1001099 PLoS Biol.
1545-7885
21765802
10.1371/journal.pbio.1001099
http://hdl.handle.net/10033/209489
PLoS biology
Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH⁻/⁻ mice) as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH⁻/⁻-induced pluripotent stem cells (iPS cells) as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH⁻/⁻ iPS cell lines, we aggregated FAH⁻/⁻-iPS cells with tetraploid embryos and obtained entirely FAH⁻/⁻-iPS cell-derived mice that were viable and exhibited the phenotype of the founding FAH⁻/⁻ mice. Then, we transduced FAH cDNA into the FAH⁻/⁻-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell-derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione). Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR)-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV)-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models.
en
Animals
Cell Survival
Cells, Cultured
Chromosomes
Cyclohexanones
Disease Models, Animal
Female
Fetus
Fibroblasts
Gene Therapy
Genetic Complementation Test
Genetic Vectors
Humans
Hydrolases
Induced Pluripotent Stem Cells
Lentivirus
Liver
Mice
Mice, Knockout
Nitrobenzoates
Pregnancy
Promoter Regions, Genetic
Spleen Focus-Forming Viruses
Tetraploidy
Tyrosinemias
Generation of healthy mice from gene-corrected disease-specific induced pluripotent stem cells.
Article
2018-06-12T20:02:56Z
Using the murine model of tyrosinemia type 1 (fumarylacetoacetate hydrolase [FAH] deficiency; FAH⁻/⁻ mice) as a paradigm for orphan disorders, such as hereditary metabolic liver diseases, we evaluated fibroblast-derived FAH⁻/⁻-induced pluripotent stem cells (iPS cells) as targets for gene correction in combination with the tetraploid embryo complementation method. First, after characterizing the FAH⁻/⁻ iPS cell lines, we aggregated FAH⁻/⁻-iPS cells with tetraploid embryos and obtained entirely FAH⁻/⁻-iPS cell-derived mice that were viable and exhibited the phenotype of the founding FAH⁻/⁻ mice. Then, we transduced FAH cDNA into the FAH⁻/⁻-iPS cells using a third-generation lentiviral vector to generate gene-corrected iPS cells. We could not detect any chromosomal alterations in these cells by high-resolution array CGH analysis, and after their aggregation with tetraploid embryos, we obtained fully iPS cell-derived healthy mice with an astonishing high efficiency for full-term development of up to 63.3%. The gene correction was validated functionally by the long-term survival and expansion of FAH-positive cells of these mice after withdrawal of the rescuing drug NTBC (2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione). Furthermore, our results demonstrate that both a liver-specific promoter (transthyretin, TTR)-driven FAH transgene and a strong viral promoter (from spleen focus-forming virus, SFFV)-driven FAH transgene rescued the FAH-deficiency phenotypes in the mice derived from the respective gene-corrected iPS cells. In conclusion, our data demonstrate that a lentiviral gene repair strategy does not abrogate the full pluripotent potential of fibroblast-derived iPS cells, and genetic manipulation of iPS cells in combination with tetraploid embryo aggregation provides a practical and rapid approach to evaluate the efficacy of gene correction of human diseases in mouse models.
ORIGINAL
Wu et al_final.pdf
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10033/209489
oai:hzi.openrepository.com:10033/209489
2019-08-30 11:32:17.162
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2184112019-08-30T11:37:44Zcom_10033_196529com_10033_56876col_10033_196534
Koenig, S
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Yuan, Q
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Krause, P
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Christiansen, H
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Rave-Fraenk, M
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Kafert-Kasting, S
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Kriegbaum, H
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Schneider, A
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Ott, M
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Meyburg, J
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Department of General and Visceral Surgery, University Medical Centre Goettingen, Goettingen, Germany. skoenig1@gwdg.de
2012-04-13T13:58:21Z
2012-04-13T13:58:21Z
2011
Regional transient portal ischemia and irradiation as preparative regimen for hepatocyte transplantation. 2011, 20 (2):303-11 Cell Transplant
1555-3892
20719089
10.3727/096368910X520074
http://hdl.handle.net/10033/218411
Cell transplantation
Hepatocyte transplantation is regarded as a promising option to correct hereditary metabolic liver disease. This study describes a novel method involving regional transient portal ischemia (RTPI) in combination with hepatic irradiation (IR) as a preparative regimen for hepatocyte transplantation. The right lobules of rat livers (45% of liver mass) were subjected to RTPI of 30-120 min. Liver specimens and serum samples were analyzed for transaminase levels, DNA damage, apoptosis, and proliferation. Repopulation experiments involved livers of dipeptidylpeptidase IV (DPPIV)-deficient rats preconditioned with RTPI (60-90 min) either with or without prior partial hepatic IR (25 Gy). After reperfusion intervals of 1 and 24 h, 12 million wild-type (DPPIV positive) hepatocytes were transplanted into recipient livers via the spleen. RTPI of 60-90 min caused limited hepatic injury through necrosis and induced a distinct regenerative response in the host liver. Twelve weeks following transplantation, small clusters of donor hepatocytes were detected within the portal areas. Quantitative analysis revealed limited engraftment of 0.79% to 2.95%, whereas control animals (sham OP) exhibited 4.16% (determined as relative activity of DPPIV when compared to wild-type liver). Repopulation was significantly enhanced (21.43%) when IR was performed prior to RTPI, optimum preconditioning settings being 90 min of ischemia and 1 h of reperfusion before transplantation. We demonstrate that RTPI alone is disadvantageous to donor cell engraftment, whereas the combination of IR with RTPI comprises an effective preparative regimen for liver repopulation. The method described clearly has potential for clinical application.
en
Archived with thanks to Cell transplantation
Alanine Transaminase
Animals
Aspartate Aminotransferases
Biological Assay
Hepatocytes
Ischemia
Liver
Liver Regeneration
Luminescence
Proliferating Cell Nuclear Antigen
Radiation, Ionizing
Rats
Rats, Inbred F344
Time Factors
Transplantation Conditioning
Regional transient portal ischemia and irradiation as preparative regimen for hepatocyte transplantation.
Article
2018-06-12T21:41:28Z
Hepatocyte transplantation is regarded as a promising option to correct hereditary metabolic liver disease. This study describes a novel method involving regional transient portal ischemia (RTPI) in combination with hepatic irradiation (IR) as a preparative regimen for hepatocyte transplantation. The right lobules of rat livers (45% of liver mass) were subjected to RTPI of 30-120 min. Liver specimens and serum samples were analyzed for transaminase levels, DNA damage, apoptosis, and proliferation. Repopulation experiments involved livers of dipeptidylpeptidase IV (DPPIV)-deficient rats preconditioned with RTPI (60-90 min) either with or without prior partial hepatic IR (25 Gy). After reperfusion intervals of 1 and 24 h, 12 million wild-type (DPPIV positive) hepatocytes were transplanted into recipient livers via the spleen. RTPI of 60-90 min caused limited hepatic injury through necrosis and induced a distinct regenerative response in the host liver. Twelve weeks following transplantation, small clusters of donor hepatocytes were detected within the portal areas. Quantitative analysis revealed limited engraftment of 0.79% to 2.95%, whereas control animals (sham OP) exhibited 4.16% (determined as relative activity of DPPIV when compared to wild-type liver). Repopulation was significantly enhanced (21.43%) when IR was performed prior to RTPI, optimum preconditioning settings being 90 min of ischemia and 1 h of reperfusion before transplantation. We demonstrate that RTPI alone is disadvantageous to donor cell engraftment, whereas the combination of IR with RTPI comprises an effective preparative regimen for liver repopulation. The method described clearly has potential for clinical application.
ORIGINAL
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/2514412019-08-30T11:28:51Zcom_10033_196529com_10033_56876col_10033_196534
Waern, Johan M
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Yuan, Qinggong
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Rüdrich, Urda
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Becker, Pablo D
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Schulze, Kai
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http://orcid.org/0000-0003-2286-3416
Strick-Marchand, Helene
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Huntington, Nicholas D
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Zacher, Behrend J
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Wursthorn, Karsten
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Disanto, James P
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Guzman, Carlos A
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Manns, Michael P
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Ott, Michael
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Bock, Michael
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Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany; Medical and Oncology Clinic, Södra Älvsborgs Sjukhus, Borås, Sweden.
2012-11-08T14:47:05Z
2012-11-08T14:47:05Z
2012-10
Ectopic expression of murine CD47 minimizes macrophage rejection of human hepatocyte xenografts in immunodeficient mice. 2012, 56 (4):1479-88 Hepatology
1527-3350
22535707
10.1002/hep.25816
http://hdl.handle.net/10033/251441
Hepatology (Baltimore, Md.)
Macrophages play an important role in the rejection of xenogeneic cells and therefore represent a major obstacle to generating chimeric mice with human xenografts that are useful tools for basic and preclinical medical research. The signal inhibitory regulatory protein α (SIRPα) receptor is a negative regulator of macrophage phagocytic activity and interacts in a species-specific fashion with its ligand CD47. Furthermore, SIRPα polymorphism in laboratory mouse strains significantly affects the extent of human CD47-mediated toleration of human xenotransplants. Aiming to minimize macrophage activity and thus optimize human cell engraftment in immunodeficient mice, we lentivirally transduced murine CD47 (Cd47) into human liver cells. Human HepG2 liver cells expressing Cd47 were less frequently contacted and phagocytosed by murine RAW264.7 macrophages in vitro than their Cd47-negative counterparts. For the generation of human-mouse chimeric livers in immunodeficient BALB-ΔRAG/γ(c) -uPA (urokinase-type plasminogen activator) mice, freshly thawed cryopreserved human hepatocytes were transduced with a lentiviral expression vector for Cd47 using a refined in vitro transduction protocol immediately before transplantation. In vivo, Cd47-positive human primary hepatocytes were selectively retained following engraftment in immunodeficient mice, leading to at least a doubling of liver repopulation efficiencies. Conclusion: We conclude that ectopic expression of murine Cd47 in human hepatocytes selectively favors engraftment upon transplantation into mice, a finding that should have a profound impact on the generation of robust humanized small animal models. Moreover, dominance of ectopically expressed murine Cd47 over endogenous human CD47 should also widen the spectrum of immunodeficient mouse strains suitable for humanization. (HEPATOLOGY 2012).
en
Archived with thanks to Hepatology (Baltimore, Md.)
Ectopic expression of murine CD47 minimizes macrophage rejection of human hepatocyte xenografts in immunodeficient mice.
Article
2013-10-15T00:00:00Z
Macrophages play an important role in the rejection of xenogeneic cells and therefore represent a major obstacle to generating chimeric mice with human xenografts that are useful tools for basic and preclinical medical research. The signal inhibitory regulatory protein α (SIRPα) receptor is a negative regulator of macrophage phagocytic activity and interacts in a species-specific fashion with its ligand CD47. Furthermore, SIRPα polymorphism in laboratory mouse strains significantly affects the extent of human CD47-mediated toleration of human xenotransplants. Aiming to minimize macrophage activity and thus optimize human cell engraftment in immunodeficient mice, we lentivirally transduced murine CD47 (Cd47) into human liver cells. Human HepG2 liver cells expressing Cd47 were less frequently contacted and phagocytosed by murine RAW264.7 macrophages in vitro than their Cd47-negative counterparts. For the generation of human-mouse chimeric livers in immunodeficient BALB-ΔRAG/γ(c) -uPA (urokinase-type plasminogen activator) mice, freshly thawed cryopreserved human hepatocytes were transduced with a lentiviral expression vector for Cd47 using a refined in vitro transduction protocol immediately before transplantation. In vivo, Cd47-positive human primary hepatocytes were selectively retained following engraftment in immunodeficient mice, leading to at least a doubling of liver repopulation efficiencies. Conclusion: We conclude that ectopic expression of murine Cd47 in human hepatocytes selectively favors engraftment upon transplantation into mice, a finding that should have a profound impact on the generation of robust humanized small animal models. Moreover, dominance of ectopically expressed murine Cd47 over endogenous human CD47 should also widen the spectrum of immunodeficient mouse strains suitable for humanization. (HEPATOLOGY 2012).
ORIGINAL
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/3173112019-08-30T11:30:32Zcom_10033_196529com_10033_56876col_10033_196534
Berneman-Zeitouni, Dana
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Molakandov, Kfir
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Mor, Eytan
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Fornoni, Alessia
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Domínguez, Miriam Ramírez
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Kerr-Conte, Julie
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Ott, Michael
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Meivar-Levy, Irit
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Ferber, Sarah
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Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany; Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany
2014-05-22T13:37:30Z
2014-05-22T13:37:30Z
2014
The temporal and hierarchical control of transcription factors-induced liver to pancreas transdifferentiation. 2014, 9 (2):e87812 PLoS ONE
1932-6203
24504462
10.1371/journal.pone.0087812
http://hdl.handle.net/10033/317311
PloS one
Lineage-specific transcription factors (TFs) display instructive roles in directly reprogramming adult cells into alternate developmental fates, in a process known as transdifferentiation. The present study analyses the hypothesis that despite being fast, transdifferentiation does not occur in one step but is rather a consecutive and hierarchical process. Using ectopic expression of Pdx1 in human liver cells, we demonstrate that while glucagon and somatostatin expression initiates within a day, insulin gene expression becomes evident only 2-3 days later. To both increase transdifferentiation efficiency and analyze whether the process indeed display consecutive and hierarchical characteristics, adult human liver cells were treated by three pancreatic transcription factors, Pdx1, Pax4 and Mafa (3pTFs) that control distinct hierarchical stages of pancreatic development in the embryo. Ectopic expression of the 3pTFs in human liver cells, increased the transdifferentiation yield, manifested by 300% increase in the number of insulin positive cells, compared to each of the ectopic factors alone. However, only when the 3pTFs were sequentially supplemented one day apart from each other in a direct hierarchical manner, the transdifferentiated cells displayed increased mature β-cell-like characteristics. Ectopic expression of Pdx1 followed by Pax4 on the 2(nd) day and concluded by Mafa on the 3(rd) day resulted in increased yield of transdifferentiation that was associated by increased glucose regulated c-peptide secretion. By contrast, concerted or sequential administration of the ectopic 3pTFs in an indirect hierarchical mode resulted in the generation of insulin and somatostatin co-producing cells and diminished glucose regulated processed insulin secretion. In conclusion transcription factors induced liver to pancreas transdifferentiation is a progressive and hierarchical process. It is reasonable to assume that this characteristic is general to wide ranges of tissues. Therefore, our findings could facilitate the development of cell replacement therapy modalities for many degenerative diseases including diabetes.
en
Archived with thanks to PloS one
The temporal and hierarchical control of transcription factors-induced liver to pancreas transdifferentiation.
Article
2018-06-13T15:36:24Z
Lineage-specific transcription factors (TFs) display instructive roles in directly reprogramming adult cells into alternate developmental fates, in a process known as transdifferentiation. The present study analyses the hypothesis that despite being fast, transdifferentiation does not occur in one step but is rather a consecutive and hierarchical process. Using ectopic expression of Pdx1 in human liver cells, we demonstrate that while glucagon and somatostatin expression initiates within a day, insulin gene expression becomes evident only 2-3 days later. To both increase transdifferentiation efficiency and analyze whether the process indeed display consecutive and hierarchical characteristics, adult human liver cells were treated by three pancreatic transcription factors, Pdx1, Pax4 and Mafa (3pTFs) that control distinct hierarchical stages of pancreatic development in the embryo. Ectopic expression of the 3pTFs in human liver cells, increased the transdifferentiation yield, manifested by 300% increase in the number of insulin positive cells, compared to each of the ectopic factors alone. However, only when the 3pTFs were sequentially supplemented one day apart from each other in a direct hierarchical manner, the transdifferentiated cells displayed increased mature β-cell-like characteristics. Ectopic expression of Pdx1 followed by Pax4 on the 2(nd) day and concluded by Mafa on the 3(rd) day resulted in increased yield of transdifferentiation that was associated by increased glucose regulated c-peptide secretion. By contrast, concerted or sequential administration of the ectopic 3pTFs in an indirect hierarchical mode resulted in the generation of insulin and somatostatin co-producing cells and diminished glucose regulated processed insulin secretion. In conclusion transcription factors induced liver to pancreas transdifferentiation is a progressive and hierarchical process. It is reasonable to assume that this characteristic is general to wide ranges of tissues. Therefore, our findings could facilitate the development of cell replacement therapy modalities for many degenerative diseases including diabetes.
ORIGINAL
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2019-08-30 11:30:32.171
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/3251702020-06-30T13:26:39Zcom_10033_196529com_10033_56876col_10033_196534
Straub, Beate K
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Rickelt, Steffen
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Zimbelmann, Ralf
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Grund, Christine
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Kuhn, Caecilia
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Iken, Marcus
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Ott, Michael
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Franke, Werner W
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2014-08-25T13:08:29Z
2014-08-25T13:08:29Z
2011-11-28
E-N-cadherin heterodimers define novel adherens junctions connecting endoderm-derived cells. 2011, 195 (5):873-87 J. Cell Biol.
1540-8140
22105347
10.1083/jcb.201106023
http://hdl.handle.net/10033/325170
The Journal of cell biology
Intercellular junctions play a pivotal role in tissue development and function and also in tumorigenesis. In epithelial cells, decrease or loss of E-cadherin, the hallmark molecule of adherens junctions (AJs), and increase of N-cadherin are widely thought to promote carcinoma progression and metastasis. In this paper, we show that this "cadherin switch" hypothesis does not hold for diverse endoderm-derived cells and cells of tumors derived from them. We show that the cadherins in a major portion of AJs in these cells can be chemically cross-linked in E-N heterodimers. We also show that cells possessing E-N heterodimer AJs can form semistable hemihomotypic AJs with purely N-cadherin-based AJs of mesenchymally derived cells, including stroma cells. We conclude that these heterodimers are the major AJ constituents of several endoderm-derived tissues and tumors and that the prevailing concept of antagonistic roles of these two cadherins in developmental and tumor biology has to be reconsidered.
en
Archived with thanks to The Journal of cell biology
Adherens Junctions
Animals
Cadherins
Cattle
Cell Adhesion
Endoderm
Humans
Mice
Rats
Swine
Tumor Cells, Cultured
E-N-cadherin heterodimers define novel adherens junctions connecting endoderm-derived cells.
Article
2018-06-12T22:01:10Z
Intercellular junctions play a pivotal role in tissue development and function and also in tumorigenesis. In epithelial cells, decrease or loss of E-cadherin, the hallmark molecule of adherens junctions (AJs), and increase of N-cadherin are widely thought to promote carcinoma progression and metastasis. In this paper, we show that this "cadherin switch" hypothesis does not hold for diverse endoderm-derived cells and cells of tumors derived from them. We show that the cadherins in a major portion of AJs in these cells can be chemically cross-linked in E-N heterodimers. We also show that cells possessing E-N heterodimer AJs can form semistable hemihomotypic AJs with purely N-cadherin-based AJs of mesenchymally derived cells, including stroma cells. We conclude that these heterodimers are the major AJ constituents of several endoderm-derived tissues and tumors and that the prevailing concept of antagonistic roles of these two cadherins in developmental and tumor biology has to be reconsidered.
ORIGINAL
Straub et al_final.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5504892020-06-30T13:26:39Zcom_10033_196529com_10033_56876col_10033_196534
Cantz, Tobias
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Sharma, Amar Deep
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Ott, Michael
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TWINCORE, Centre for Experimental and Clinical Infection Research, Feodor-Lynen Str. 7, 30625, Hannover, Germany.
2015-04-23T09:35:22Z
2015-04-23T09:35:22Z
2015-04
Concise review: cell therapies for hereditary metabolic liver diseases-concepts, clinical results, and future developments. 2015, 33 (4):1055-62 Stem Cells
1549-4918
25524146
10.1002/stem.1920
http://hdl.handle.net/10033/550489
Stem cells (Dayton, Ohio)
The concept of cell-based therapies for inherited metabolic liver diseases has been introduced for now more than 40 years in animal experiments, but controlled clinical data in humans are still not available. In the era of dynamic developments in stem cell science, the "right" cell for transplantation is considered as an important key for successful treatment. Do we aim to transplant mature hepatocytes or do we consider the liver as a stem/progenitor-driven organ and replenish the diseased liver with genetically normal stem/progenitor cells? Although conflicting results from cell tracing and transplantation experiments have recently emerged about the existence and role of stem/progenitor cells in the liver, their overall contribution to parenchymal cell homeostasis and tissue repair is limited. Accordingly, engraftment and repopulation efficacies of extrahepatic and liver-derived stem/progenitor cell types are considered to be lower compared to mature hepatocytes. On the basis of these results, we will discuss the current clinical cell transplantation programs for inherited metabolic liver diseases and future developments in liver cell therapy. Stem Cells 2015;33:1055-1062.
en
Concise review: cell therapies for hereditary metabolic liver diseases-concepts, clinical results, and future developments.
Article
2018-06-12T23:38:04Z
The concept of cell-based therapies for inherited metabolic liver diseases has been introduced for now more than 40 years in animal experiments, but controlled clinical data in humans are still not available. In the era of dynamic developments in stem cell science, the "right" cell for transplantation is considered as an important key for successful treatment. Do we aim to transplant mature hepatocytes or do we consider the liver as a stem/progenitor-driven organ and replenish the diseased liver with genetically normal stem/progenitor cells? Although conflicting results from cell tracing and transplantation experiments have recently emerged about the existence and role of stem/progenitor cells in the liver, their overall contribution to parenchymal cell homeostasis and tissue repair is limited. Accordingly, engraftment and repopulation efficacies of extrahepatic and liver-derived stem/progenitor cell types are considered to be lower compared to mature hepatocytes. On the basis of these results, we will discuss the current clinical cell transplantation programs for inherited metabolic liver diseases and future developments in liver cell therapy. Stem Cells 2015;33:1055-1062.
ORIGINAL
Cantz, Sharma and Ott_final.pdf
Cantz, Sharma and Ott_final.pdf
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TEXT
Cantz, Sharma and Ott_final.pdf.txt
Cantz, Sharma and Ott_final.pdf.txt
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THUMBNAIL
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Cantz, Sharma and Ott_final.pdf.jpg
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oai:repository.helmholtz-hzi.de:10033/550489
2020-06-30 13:26:39.521
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/5969252019-08-30T11:37:00Zcom_10033_196529com_10033_56876col_10033_196534
Klett-Tammen, Carolina J
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Krause, Gerard
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Seefeld, Linda
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Ott, Jördis J
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2016-02-22T14:20:09Z
2016-02-22T14:20:09Z
2016
Determinants of tetanus, pneumococcal and influenza vaccination in the elderly: a representative cross-sectional study on knowledge, attitude and practice (KAP). 2016, 16 (1):121 BMC Public Health
1471-2458
26846202
10.1186/s12889-016-2784-8
http://hdl.handle.net/10033/596925
BMC public health
Severity and incidence of vaccine-preventable infections with influenza viruses, s. pneumoniae and c. tetani increase with age. Furthermore, vaccine coverage in the elderly is often insufficient. The aim of this study is to identify socio-economic and knowledge-, attitude- and practice- (KAP)-related determinants of vaccination against influenza, pneumococcal disease and tetanus in the older German population.
en
Determinants of tetanus, pneumococcal and influenza vaccination in the elderly: a representative cross-sectional study on knowledge, attitude and practice (KAP).
Article
2018-06-13T07:24:15Z
Severity and incidence of vaccine-preventable infections with influenza viruses, s. pneumoniae and c. tetani increase with age. Furthermore, vaccine coverage in the elderly is often insufficient. The aim of this study is to identify socio-economic and knowledge-, attitude- and practice- (KAP)-related determinants of vaccination against influenza, pneumococcal disease and tetanus in the older German population.
ORIGINAL
Klett-Tammen et al.pdf
Klett-Tammen et al.pdf
Open Access publication
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TEXT
Klett-Tammen et al.pdf.txt
Klett-Tammen et al.pdf.txt
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THUMBNAIL
Klett-Tammen et al.pdf.jpg
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6199942020-06-30T13:26:39Zcom_10033_196529com_10033_56876col_10033_196534
Yang, Dakai
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Balakrishnan, Asha
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Bantel, Heike
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Klusmann, Jan-Henning
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Manns, Michael P
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Ott, Michael
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Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.
2016-09-08T09:45:44Z
2016-09-08T09:45:44Z
2016
MicroRNA-125b-5p mimic inhibits acute liver failure. 2016, 7:11916 Nat Commun
2041-1723
27336362
10.1038/ncomms11916
http://hdl.handle.net/10033/619994
Nature communications
The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
MicroRNA-125b-5p mimic inhibits acute liver failure.
Article
2018-06-12T16:58:14Z
The lack of broad-spectrum anti-acute liver failure (ALF) therapeutic agents contributes to ALF-related mortality. MicroRNAs (miRNAs) are suggested to be potent serum biomarkers for ALF, but their functional and therapeutic relevance in ALF are unclear. Here we show an unbiased approach, using two complementary miRNA screens, to identify miRNAs that can attenuate ALF. We identify miR-125b-5p as a regulator of cell death that attenuates paracetamol-induced and FAS-induced toxicity in mouse and human hepatocytes. Importantly, administration of miR-125b-5p mimic in mouse liver prevents injury and improves survival in models of ALF. Functional studies show that miR-125b-5p ameliorates ALF by directly regulating kelch-like ECH-associated protein 1, in turn elevating expression of nuclear factor-E2-related factor 2, a known regulator in ALF. Collectively, our findings establish miR-125b-5p as an important regulator of paracetamol-induced and FAS-induced cell death. Thus, miR-125b-5p mimic may serve as a broad-spectrum therapeutic attenuator of cell death during ALF.
ORIGINAL
Yang et al.pdf
Yang et al.pdf
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2020-06-30 13:26:39.593
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/6213362020-06-30T13:26:39Zcom_10033_196529com_10033_56876com_10033_6839col_10033_196534col_10033_621495
Junge, Norman
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Yuan, Qinggong
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Vu, Thu Huong
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Krooss, Simon
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Bednarski, Christien
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Balakrishnan, Asha
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Cathomen, Toni
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Manns, Michael P
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Baumann, Ulrich
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Sharma, Amar Deep
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TWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
2018-04-05T11:55:04Z
2018-04-05T11:55:04Z
2018-02-27
Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model. 2018, 10 (2):277-286 World J Hepatol
1948-5182
29527263
10.4254/wjh.v10.i2.277
http://hdl.handle.net/10033/621336
World journal of hepatology
To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout (Fah-/-)mice by homologous-recombination-mediated targeted addition of theFahgene.
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
Homologous recombination mediates stable Fah gene integration and phenotypic correction in tyrosinaemia mouse-model.
Article
2018-05-23T10:55:13Z
To stably correct tyrosinaemia in proliferating livers of fumarylacetoacetate-hydrolase knockout (Fah-/-)mice by homologous-recombination-mediated targeted addition of theFahgene.
ORIGINAL
Junge et al.pdf
Junge et al.pdf
Open Access article
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Helmholtz Zentrum für Infektionsforschung Repository
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oai:repository.helmholtz-hzi.de:10033/6218402019-08-30T11:26:09Zcom_10033_196529com_10033_56876col_10033_196534
Ott, Michael
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Castell, Jose V
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TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.
2019-07-02T13:00:25Z
2019-07-02T13:00:25Z
2019-06-01
J Hepatol. 2019 Jun;70(6):1049-1050. doi: 10.1016/j.jhep.2019.03.022. Epub 2019 Apr 17.
1600-0641
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10.1016/j.jhep.2019.03.022
http://hdl.handle.net/10033/621840
Journal of Hepatology
Editorial
Elsevier
Attribution-NonCommercial-ShareAlike 4.0 International
http://creativecommons.org/licenses/by-nc-sa/4.0/
Hepatocyte transplantation, a step forward?
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Journal of hepatology
THUMBNAIL
2020-06-06
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TEXT
2020-06-06
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Helmholtz Zentrum für Infektionsforschung Repository
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