135 results match your criteria: "Oregon Stem Cell Center[Affiliation]"
Mol Metab
January 2015
Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR 97239, USA ; Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
Objective: Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high-fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD.
View Article and Find Full Text PDFStem Cell Reports
January 2015
Oregon Stem Cell Center, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
Androgens are widely used for treating Fanconi anemia (FA) and other human bone marrow failure syndromes, but their mode of action remains incompletely understood. Aged Fancd2(-/-) mice were used to assess the therapeutic efficacy of oxymetholone (OXM) and its mechanism of action. Eighteen-month-old Fancd2(-/-) mice recapitulated key human FA phenotypes, including reduced bone marrow cellularity, red cell macrocytosis, and peripheral pancytopenia.
View Article and Find Full Text PDFCell Stem Cell
September 2014
Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Stem Cell Center, L 321, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address:
Facultative liver stem cells have long been thought to be an important source of new hepatocytes during chronic liver injury. This longstanding paradigm is being challenged by two papers discussed herein (Schaub et al., 2014; Yanger et al.
View Article and Find Full Text PDFStem Cell Res
September 2014
Oregon Stem Cell Center, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address:
Pancreatic Lgr5 expression has been associated with organoid-forming epithelial progenitor populations but the identity of the organoid-initiating epithelial cell subpopulation has remained elusive. Injury causes the emergence of an Lgr5(+) organoid-forming epithelial progenitor population in the adult mouse liver and pancreas. Here, we define the origin of organoid-initiating cells from mouse pancreas and liver prior to Lgr5 activation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
June 2014
Department of Molecular and Medical Genetics and
The transcription factor c-MYC is stabilized and activated by phosphorylation at serine 62 (S62) in breast cancer. Protein phosphatase 2A (PP2A) is a critical negative regulator of c-MYC through its ability to dephosphorylate S62. By inactivating c-MYC and other key signaling pathways, PP2A plays an important tumor suppressor function.
View Article and Find Full Text PDFStem Cell Res
July 2014
Division of Transplant Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA. Electronic address:
Hereditary tyrosinemia type I (HT1) is caused by deficiency in fumarylacetoacetate hydrolase (FAH), an enzyme that catalyzes the last step of tyrosine metabolism. The most severe form of the disease presents acutely during infancy, and is characterized by severe liver involvement, most commonly resulting in death if untreated. Generation of FAH(+/-) pigs was previously accomplished by adeno-associated virus-mediated gene knockout in fibroblasts and somatic cell nuclear transfer.
View Article and Find Full Text PDFMol Endocrinol
July 2014
Department of Integrative Physiology and Neuroscience (M.D., M.Z., T.J.L., T.B., I.N.K., S.M.A., G.A.W.), Program in Neuroscience, Washington State University, Pullman, Washington 99164; Oregon Stem Cell Center (S.I.), Oregon Health and Sciences University, Portland, Oregon 97239; and Department of Neurophysiology (T.N.), Graduate School of Medicine, University of Tokyo, Tokyo 113-0033 Japan.
Leptin acts in the hippocampus to enhance cognition and reduce depression and anxiety. Cognitive and emotional disorders are associated with abnormal hippocampal dendritic spine formation and synaptogenesis. Although leptin has been shown to induce synaptogenesis in the hypothalamus, its effects on hippocampal synaptogenesis and the mechanism(s) involved are not well understood.
View Article and Find Full Text PDFPLoS One
December 2014
Dept. of Medicine, Division of GI & Hepatology, Oregon Health & Science Center, Portland, Oregon, United States of America; Oregon Stem Cell Center, Oregon Health & Science Center, Portland, Oregon, United States of America.
Background & Aims: Many signals governing liver regeneration (LR) following 2/3 partial hepatectomy (PH) are recognized, but the primary signal(s) remains unknown. The aim of the study was to confirm that the remnant liver after PH lacks capacity to secrete the BA pool returning via the enterohepatic ciruculation (EHC), which may in turn stimulate LR.
Methods: After standard PH, BA flux was documented and BA signaling (Fgf15) and synthesis (Cyp7a) determined by qPCR.
Blood
July 2014
Division of Hematology/Oncology, Stem Cell Program, and Harvard Medical School, Boston, MA; Harvard Stem Cell Institute, Cambridge, MA.
Pearson marrow pancreas syndrome (PS) is a multisystem disorder caused by mitochondrial DNA (mtDNA) deletions. Diamond-Blackfan anemia (DBA) is a congenital hypoproliferative anemia in which mutations in ribosomal protein genes and GATA1 have been implicated. Both syndromes share several features including early onset of severe anemia, variable nonhematologic manifestations, sporadic genetic occurrence, and occasional spontaneous hematologic improvement.
View Article and Find Full Text PDFNat Biotechnol
June 2014
1] David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3] Harvard-MIT Division of Health Sciences & Technology, Cambridge, Massachusetts, USA. [4] Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
We demonstrate CRISPR-Cas9-mediated correction of a Fah mutation in hepatocytes in a mouse model of the human disease hereditary tyrosinemia. Delivery of components of the CRISPR-Cas9 system by hydrodynamic injection resulted in initial expression of the wild-type Fah protein in ∼1/250 liver cells. Expansion of Fah-positive hepatocytes rescued the body weight loss phenotype.
View Article and Find Full Text PDFMol Cancer Res
June 2014
Authors' Affiliations: Departments of Molecular and Medical Genetics,
Unlabelled: Pancreatic cancer is a deadly disease that is usually diagnosed in the advanced stages when few effective therapies are available. Given the aggressive clinical course of this disease and lack of good treatment options, the development of new therapeutic agents for the treatment of pancreatic cancer is of the upmost importance. Several pathways that have shown to contribute to pancreatic cancer progression are negatively regulated by the tumor suppressor protein phosphatase 2A (PP2A).
View Article and Find Full Text PDFBlood
May 2014
Vollum Institute, Howard Hughes Medical Institute, Portland, OR.
The corepressor Rcor1 has been linked biochemically to hematopoiesis, but its function in vivo remains unknown. We show that mice deleted for Rcor1 are profoundly anemic and die in late gestation. Definitive erythroid cells from mutant mice arrest at the transition from proerythroblast to basophilic erythroblast.
View Article and Find Full Text PDFLeukemia
October 2014
Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health & Sciences University, Portland, OR.
Nucleic Acids Res
April 2014
Department of Pediatrics, Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR 97239, USA, Department of Surgery/Surgical Oncology, Oregon Health & Science University, Portland, OR 97239, USA, Center for Biomedical Education and Research, Institute of Cell Biology, University of Witten/Herdecke, Witten 58453, Germany, Oregon Stem Cell Center, Oregon Health & Science University, Portland, OR 97239, USA and Department of Cell & Developmental Biology Oregon Health & Science University, Portland, OR 97239, USA.
Insertional oncogene activation and aberrant splicing have proved to be major setbacks for retroviral stem cell gene therapy. Integrase-deficient human immunodeficiency virus-1-derived vectors provide a potentially safer approach, but their circular genomes are rapidly lost during cell division. Here we describe a novel lentiviral vector (LV) that incorporates human ß-interferon scaffold/matrix-associated region sequences to provide an origin of replication for long-term mitotic maintenance of the episomal LTR circles.
View Article and Find Full Text PDFJ Neurosci
January 2014
Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington 99164, Department of Molecular Biosciences, University of California, Davis, California 95616, and Oregon Stem Cell Center, Oregon Health and Science University, Portland, Oregon 97239.
Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) are widespread environmental contaminants linked to neuropsychological dysfunction in children. NDL PCBs increase spontaneous Ca(2+) oscillations in neurons by stabilizing ryanodine receptor (RyR) calcium release channels in the open configuration, which results in CREB-dependent dendritic outgrowth. In this study, we address the question of whether activation of CREB by NDL PCBs also triggers dendritic spine formation.
View Article and Find Full Text PDFNature
February 2014
Stanford University, School of Medicine, Departments of Pediatrics and Genetics, 269 Campus Drive, Stanford, California 94305, USA.
Biol Blood Marrow Transplant
January 2014
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon. Electronic address:
Human cytomegalovirus (HCMV) infection, including primary infection resulting from transmission from a seropositive donor to a seronegative recipient (D(+)/R(-)), remains a significant problem in the setting of peripheral blood stem cell transplantation (PBSCT). The lack of a suitable animal model for studying HCMV transmission after PBSCT is a major barrier to understanding this process and, consequently, developing novel interventions to prevent HCMV infection. Our previous work demonstrated that human CD34(+) progenitor cell-engrafted NOD-scid IL2Rγc(null) (NSG) mice support latent HCMV infection after direct inoculation and reactivation after treatment with granulocyte colony-stimulating factor.
View Article and Find Full Text PDFPediatr Blood Cancer
April 2014
Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon.
Fanconi anemia (FA) patients suffer from progressive bone marrow failure and often develop cancers. Previous studies showed that antioxidants tempol and resveratrol (RV) delayed tumor onset and reduced hematologic defects in FA murine models, respectively. Here we tested whether antioxidants N-acetylcysteine (NAC) or RV could delay cancer in tumor prone Fancd2(-/-) /Trp53(+/-) mice.
View Article and Find Full Text PDFGut
September 2014
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Background And Aims: The cyclin-dependent kinase inhibitor p21 has been implicated as a tumour suppressor. Moreover, recent genetic studies suggest that p21 might be a potential therapeutic target to improve regeneration in chronic diseases. The aim of this study was to delineate the role of p21 in chronic liver injury and to specify its role in hepatocarcinogenesis in a mouse model of chronic cholestatic liver injury.
View Article and Find Full Text PDFGastroenterology
December 2013
Oregon Stem Cell Center, Department of Pediatrics, Oregon Health & Science University, Portland, Oregon. Electronic address:
Animal models are used to study many aspects of human disease and to test therapeutic interventions. However, some very important features of human biology cannot be replicated in animals, even in nonhuman primates or transgenic rodents engineered with human genes. Most human microbial pathogens do not infect animals and the metabolism of many xenobiotics is different between human beings and animals.
View Article and Find Full Text PDFStem Cell Res
November 2013
Papé Family Pediatric Research Institute, Oregon Stem Cell Center, Department of Pediatrics, Portland, OR, USA.
Endothelial cells (ECs) are an essential component of the hematopoietic microenvironment, which maintains and regulates hematopoietic stem cells (HSCs). Although ECs can support the regeneration of otherwise lethally-irradiated HSCs, the mechanisms are not well understood. To further understand this phenomenon, we studied HSC regeneration from irradiated bone marrow using co-culture with human aortic ECs (HAECs).
View Article and Find Full Text PDFStem Cell Res
September 2013
Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA.
Fanconi anemia patients suffer from progressive bone marrow failure. An overactive p53 response to DNA damage contributes to the progressive elimination of Fanconi anemia hematopoietic stem and progenitor cells (HSPC), and hence presents a potential target for therapeutic intervention. To investigate whether the cell cycle regulatory protein p21 is the primary mediator of the p53-dependent stem cell loss, p21/Fancd2 double-knockout mice were generated.
View Article and Find Full Text PDFStem Cell Res
July 2013
Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health & Science University, Portland, OR 97203, USA.
Cell replacement is an emerging therapy for type 1 diabetes. Pluripotent stem cells have received a lot of attention as a potential source of transplantable β-cells, but their ability to form teratomas poses significant risks. Here, we evaluated the potential of primary mouse gall bladder epithelial cells (GBCs) as targets for ex vivo genetic reprogramming to the β-cell fate.
View Article and Find Full Text PDFMol Ther
October 2012
Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
Although recombinant adeno-associated viral (rAAV) vectors are promising tools for gene therapy of genetic disorders, they remain mostly episomal and hence are lost during cell replication. For this reason, rAAV vectors capable of chromosomal integration would be desirable. Ribosomal DNA (rDNA) repeat sequences are overrepresented during random integration of rAAV.
View Article and Find Full Text PDFMol Ther
October 2012
Oregon Stem Cell Center, Oregon Health and Science University, Portland, Oregon 97203, USA.
Genetic fumarylacetoacetate hydrolase (Fah) deficiency is unique in that healthy gene-corrected hepatocytes have a strong growth advantage and can repopulate the diseased liver. Unfortunately, similar positive selection of gene-corrected cells is absent in most inborn errors of liver metabolism and it is difficult to reach the cell replacement index required for therapeutic benefit. Therefore, methods to transiently create a growth advantage for genetically modified hepatocytes in any genetic background would be advantageous.
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