LIVIVO - Search results -

Search results

Result 1 - 10 of total 16

Search options

Article ; Online: Lentiviral gene therapy for X-linked chronic granulomatous disease recapitulates endogenous CYBB regulation and expression.

Wong, Ryan L / Sackey, Sarah / Brown, Devin / Senadheera, Shantha / Masiuk, Katelyn / Quintos, Jason P / Colindres, Nicole / Riggan, Luke / Morgan, Richard A / Malech, Harry L / Hollis, Roger P / Kohn, Donald B

Blood

2023 Volume 141, Issue 9, Page(s) 1007–1022

Abstract: X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the CYBB gene, resulting in the inability of phagocytic cells to eliminate infections. To design a lentiviral vector (LV) capable of recapitulating the ... ...

Abstract	X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the CYBB gene, resulting in the inability of phagocytic cells to eliminate infections. To design a lentiviral vector (LV) capable of recapitulating the endogenous regulation and expression of CYBB, a bioinformatics-guided approach was used to elucidate the cognate enhancer elements regulating the native CYBB gene. Using this approach, we analyzed a 600-kilobase topologically associated domain of the CYBB gene and identified endogenous enhancer elements to supplement the CYBB promoter to develop MyeloVec, a physiologically regulated LV for the treatment of X-CGD. When compared with an LV currently in clinical trials for X-CGD, MyeloVec showed improved expression, superior gene transfer to hematopoietic stem and progenitor cells (HSPCs), corrected an X-CGD mouse model leading to complete protection against Burkholderia cepacia infection, and restored healthy donor levels of antimicrobial oxidase activity in neutrophils derived from HSPCs from patients with X-CGD. Our findings validate the bioinformatics-guided design approach and have yielded a novel LV with clinical promise for the treatment of X-CGD.
MeSH term(s)	Animals ; Mice ; Granulomatous Disease, Chronic/genetics ; Granulomatous Disease, Chronic/therapy ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism ; NADPH Oxidase 2/genetics ; Genetic Therapy/methods ; Mutation
Chemical Substances	NADPH Oxidases (EC 1.6.3.-) ; NADPH Oxidase 2 (EC 1.6.3.-) ; Cybb protein, mouse (EC 1.6.3.-)
Language	English
Publishing date	2023-03-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022016074
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uh III Zs.140: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 364: Show issues

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Global and Local Manipulation of DNA Repair Mechanisms to Alter Site-Specific Gene Editing Outcomes in Hematopoietic Stem Cells.

Benitez, Elizabeth K / Lomova Kaufman, Anastasia / Cervantes, Lilibeth / Clark, Danielle N / Ayoub, Paul G / Senadheera, Shantha / Osborne, Kyle / Sanchez, Julie M / Crisostomo, Ralph Valentine / Wang, Xiaoyan / Reuven, Nina / Shaul, Yosef / Hollis, Roger P / Romero, Zulema / Kohn, Donald B

Frontiers in genome editing

2020 Volume 2, Page(s) 601541

Abstract: Monogenic disorders of the blood system have the potential to be treated by autologous stem cell transplantation ... ...

Abstract	Monogenic disorders of the blood system have the potential to be treated by autologous stem cell transplantation of
Language	English
Publishing date	2020-12-10
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-3439
ISSN (online)	2673-3439
DOI	10.3389/fgeed.2020.601541
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.

Morgan, Richard A / Ma, Feiyang / Unti, Mildred J / Brown, Devin / Ayoub, Paul George / Tam, Curtis / Lathrop, Lindsay / Aleshe, Bamidele / Kurita, Ryo / Nakamura, Yukio / Senadheera, Shantha / Wong, Ryan L / Hollis, Roger P / Pellegrini, Matteo / Kohn, Donald B

Molecular therapy. Methods & clinical development

2020 Volume 17, Page(s) 999–1013

Abstract: Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations ... ...

Abstract	Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of
Language	English
Publishing date	2020-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2020.04.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 7107: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Integrase-defective lentiviral vectors as a delivery platform for targeted modification of adenosine deaminase locus.

Joglekar, Alok V / Hollis, Roger P / Kuftinec, Gabriela / Senadheera, Shantha / Chan, Rebecca / Kohn, Donald B

Molecular therapy : the journal of the American Society of Gene Therapy

2013 Volume 21, Issue 9, Page(s) 1705–1717

Abstract: We investigated the use of integrase-defective lentiviral vectors (IDLVs) for transient delivery of zinc finger nucleases (ZFNs) and donor templates for site-specific modification of the human adenosine deaminase (hADA) gene. Initially, we constructed ... ...

Abstract	We investigated the use of integrase-defective lentiviral vectors (IDLVs) for transient delivery of zinc finger nucleases (ZFNs) and donor templates for site-specific modification of the human adenosine deaminase (hADA) gene. Initially, we constructed IDLVs carrying ZFN monomers (Single-IDLVs) and found them to be able to deliver their gene-editing payload to K562 cells successfully upon cotransduction, with minimal cytotoxicity. To simplify delivery, we designed an IDLV construct to deliver both ZFN monomers from the same vector (Double-IDLV). However, this construct in its original state was prone to rearrangements of the vector genome, resulting in greatly reduced functionality; this was due to recombination between highly similar ZFN monomers arranged in tandem. We modified the Double-IDLV constructs to reduce recombination and restored simultaneous delivery of both ZFNs. We also tested an IDLV construct for delivery of donor templates and demonstrated its efficacy for gene modification. In summary, we highlighted the importance of modifying vector design for co-delivery of highly similar sequences inherent to genome-editing nucleases, and demonstrated significant improvement in the use of IDLVs for delivery of ZFNs and donor templates for genome modification.
MeSH term(s)	Adenosine Deaminase/genetics ; Endonucleases/genetics ; Endonucleases/metabolism ; Genetic Loci ; Genetic Vectors ; Humans ; Integrases/genetics ; K562 Cells ; Lentivirus/genetics ; Lentivirus/metabolism ; Transduction, Genetic ; Virus Integration ; Zinc Fingers
Chemical Substances	Integrases (EC 2.7.7.-) ; Endonucleases (EC 3.1.-) ; ADA protein, human (EC 3.5.4.4) ; Adenosine Deaminase (EC 3.5.4.4)
Language	English
Publishing date	2013-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1038/mt.2013.106
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5640: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Improved Titer and Gene Transfer by Lentiviral Vectors Using Novel, Small β-Globin Locus Control Region Elements.

Morgan, Richard A / Unti, Mildred J / Aleshe, Bamidele / Brown, Devin / Osborne, Kyle S / Koziol, Colin / Ayoub, Paul G / Smith, Oliver B / O'Brien, Rachel / Tam, Curtis / Miyahira, Eric / Ruiz, Marlene / Quintos, Jason P / Senadheera, Shantha / Hollis, Roger P / Kohn, Donald B

Molecular therapy : the journal of the American Society of Gene Therapy

2019 Volume 28, Issue 1, Page(s) 328–340

Abstract: β-globin lentiviral vectors (β-LV) have faced challenges in clinical translation for gene therapy of sickle cell disease (SCD) due to low titer and sub-optimal gene transfer to hematopoietic stem and progenitor cells (HSPCs). To overcome the challenge of ...

Abstract	β-globin lentiviral vectors (β-LV) have faced challenges in clinical translation for gene therapy of sickle cell disease (SCD) due to low titer and sub-optimal gene transfer to hematopoietic stem and progenitor cells (HSPCs). To overcome the challenge of preserving efficacious expression while increasing vector performance, we used published genomic and epigenomic data available through ENCODE to redefine enhancer element boundaries of the β-globin locus control region (LCR) to construct novel ENCODE core sequences. These novel LCR elements were used to design a β-LV of reduced proviral length, termed CoreGA-AS3-FB, produced at higher titers and possessing superior gene transfer to HSPCs when compared to the full-length parental β-LV at equal MOI. At low vector copy number, vectors containing the ENCODE core sequences were capable of reversing the sickle phenotype in a mouse model of SCD. These studies provide a β-LV that will be beneficial for gene therapy of SCD by significantly reducing the cost of vector production and extending the vector supply.
MeSH term(s)	Anemia, Sickle Cell/therapy ; Animals ; Bone Marrow Cells/metabolism ; Disease Models, Animal ; Genetic Therapy/methods ; Genetic Vectors ; HEK293 Cells ; Healthy Volunteers ; Hematopoietic Stem Cells/metabolism ; Humans ; Lentivirus/genetics ; Locus Control Region/genetics ; Mice ; Phenotype ; Transduction, Genetic/methods ; Transfection ; beta-Globins/genetics
Chemical Substances	beta-Globins
Language	English
Publishing date	2019-09-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2019.09.020
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5640: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Highly efficient large-scale lentiviral vector concentration by tandem tangential flow filtration.

Cooper, Aaron R / Patel, Sanjeet / Senadheera, Shantha / Plath, Kathrin / Kohn, Donald B / Hollis, Roger P

Journal of virological methods

2011 Volume 177, Issue 1, Page(s) 1–9

Abstract: Large-scale lentiviral vector (LV) concentration can be inefficient and time consuming, often involving multiple rounds of filtration and centrifugation. This report describes a simpler method using two tangential flow filtration (TFF) steps to ... ...

Abstract	Large-scale lentiviral vector (LV) concentration can be inefficient and time consuming, often involving multiple rounds of filtration and centrifugation. This report describes a simpler method using two tangential flow filtration (TFF) steps to concentrate liter-scale volumes of LV supernatant, achieving in excess of 2000-fold concentration in less than 3h with very high recovery (>97%). Large volumes of LV supernatant can be produced easily through the use of multi-layer flasks, each having 1720 cm(2) surface area and producing ∼560 mL of supernatant per flask. Combining the use of such flasks and TFF greatly simplifies large-scale production of LV. As a demonstration, the method is used to produce a very high titer LV (>10(10)TU/mL) and transduce primary human CD34+ hematopoietic stem/progenitor cells at high final vector concentrations with no overt toxicity. A complex LV (STEMCCA) for induced pluripotent stem cell (iPSC) generation is also concentrated from low initial titer and used to transduce and reprogram primary human fibroblasts with no overt toxicity. Additionally, a generalized and simple multiplexed real-time PCR assay is described for lentiviral vector titer and copy number determination.
MeSH term(s)	Animals ; Antigens, CD34/metabolism ; Cell Culture Techniques ; Cell Line, Tumor ; Centrifugation ; Fibroblasts/metabolism ; Filtration/methods ; Genetic Vectors/isolation & purification ; HT29 Cells ; Hematopoietic Stem Cells/metabolism ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Lentivirus/genetics ; Lentivirus/isolation & purification ; Mice ; Transduction, Genetic
Chemical Substances	Antigens, CD34
Language	English
Publishing date	2011-07-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2011.06.019
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1565: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: The common gamma chain (gamma c) is a required signaling component of the IL-21 receptor and supports IL-21-induced cell proliferation via JAK3.

Habib, Tania / Senadheera, Shantha / Weinberg, Kenneth / Kaushansky, Kenneth

Biochemistry

2002 Volume 41, Issue 27, Page(s) 8725–8731

Abstract: The common cytokine receptor gamma chain (gamma c), an essential component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, is critical for the development and function of lymphocytes. Recently, a novel lymphokine (IL-21) and its receptor (IL-21R ... ...

Abstract	The common cytokine receptor gamma chain (gamma c), an essential component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, is critical for the development and function of lymphocytes. Recently, a novel lymphokine (IL-21) and its receptor (IL-21R alpha) were described which profoundly affect the growth and activation state of B, T, and NK cells in concert with other lymphokines or stimuli [Parrish-Novak, J., et al. (2000) Nature 408, 57-63]. In this report, we show that gamma c is also a required signaling component of the IL-21 receptor (IL-21R) using the gamma c-deficient X-linked severe combined immunodeficiency (XSCID) lymphoblastoid cell line JT, and JT cells reconstituted with gamma c (JT/gamma c). Moreover, we demonstrate a functional requirement for both gamma c and the gamma c-associated Janus family tyrosine kinase 3 (JAK3) in IL-21-induced proliferation of pro-B-lymphoid cells engineered to express human IL-21R alpha (BaF3/IL-21R alpha). Retroviral-mediated transduction of wild-type gamma c into XSCID JT cells restored function to the IL-21R, as shown by IL-21-induced tyrosine phosphorylation of JAK1 and JAK3, and downstream activation of STAT5, in JT/gamma c cells as well as BaF3/IL-21R alpha and primary splenic B cells. In contrast, IL-21 failed to activate the JAK-STAT pathway in nonreconstituted JT cells. Monoclonal antibodies specific for the gamma c chain effectively inhibited IL-21-induced growth of BaF3/IL-21R alpha cells, supporting a functional role for this molecule in the IL-21R complex. In addition, the specific JAK3 tyrosine kinase inhibitor WHI-P131 significantly reduced IL-21-induced proliferation of BaF3/IL-21R alpha cells. Taken together, these results definitively demonstrate that IL-21-mediated signaling requires the gamma c chain, and indicate that JAK3 is an essential transducer of gamma c-dependent survival and/or mitogenic signals induced by this cytokine.
MeSH term(s)	Animals ; Cell Division/drug effects ; Interleukin-1/pharmacology ; Interleukin-21 Receptor alpha Subunit ; Janus Kinase 1 ; Mice ; Mice, SCID ; Phosphorylation ; Phosphotyrosine/metabolism ; Protein-Tyrosine Kinases/metabolism ; Receptors, Interleukin/chemistry ; Receptors, Interleukin/physiology ; Receptors, Interleukin-21 ; Signal Transduction
Chemical Substances	IL21R protein, human ; Il21r protein, mouse ; Interleukin-1 ; Interleukin-21 Receptor alpha Subunit ; Receptors, Interleukin ; Receptors, Interleukin-21 ; Phosphotyrosine (21820-51-9) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; JAK1 protein, human (EC 2.7.10.2) ; Jak1 protein, mouse (EC 2.7.10.2) ; Janus Kinase 1 (EC 2.7.10.2)
Language	English
Publishing date	2002-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1108-3
ISSN	1520-4995 ; 0006-2960
ISSN (online)	1520-4995
ISSN	0006-2960
DOI	10.1021/bi0202023
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 217: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: The human ankyrin 1 promoter insulator sustains gene expression in a β-globin lentiviral vector in hematopoietic stem cells.

Romero, Zulema / Campo-Fernandez, Beatriz / Wherley, Jennifer / Kaufman, Michael L / Urbinati, Fabrizia / Cooper, Aaron R / Hoban, Megan D / Baldwin, Kismet M / Lumaquin, Dianne / Wang, Xiaoyan / Senadheera, Shantha / Hollis, Roger P / Kohn, Donald B

Molecular therapy. Methods & clinical development

2015 Volume 2, Page(s) 15012

Abstract: Lentiviral vectors designed for the treatment of the hemoglobinopathies require the inclusion of regulatory and strong enhancer elements to achieve sufficient expression of the β-globin transgene. Despite the inclusion of these elements, the efficacy of ... ...

Abstract	Lentiviral vectors designed for the treatment of the hemoglobinopathies require the inclusion of regulatory and strong enhancer elements to achieve sufficient expression of the β-globin transgene. Despite the inclusion of these elements, the efficacy of these vectors may be limited by transgene silencing due to the genomic environment surrounding the integration site. Barrier insulators can be used to give more consistent expression and resist silencing even with lower vector copies. Here, the barrier activity of an insulator element from the human ankyrin-1 gene was analyzed in a lentiviral vector carrying an antisickling human β-globin gene. Inclusion of a single copy of the Ankyrin insulator did not affect viral titer, and improved the consistency of expression from the vector in murine erythroleukemia cells. The presence of the Ankyrin insulator element did not change transgene expression in human hematopoietic cells in short-term erythroid culture or in vivo in primary murine transplants. However, analysis in secondary recipients showed that the lentiviral vector with the Ankyrin element preserved transgene expression, whereas expression from the vector lacking the Ankyrin insulator decreased in secondary recipients. These studies demonstrate that the Ankyrin insulator may improve long-term β-globin expression in hematopoietic stem cells for gene therapy of hemoglobinopathies.
Language	English
Publishing date	2015-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1038/mtm.2015.12
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 7107: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Expansion of liver cancer stem cells during aging in methionine adenosyltransferase 1A-deficient mice.

Rountree, C Bart / Senadheera, Shantha / Mato, Jose M / Crooks, Gay M / Lu, Shelly C

Hepatology (Baltimore, Md.)

2008 Volume 47, Issue 4, Page(s) 1288–1297

Abstract: Unlabelled: Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the biosynthesis of S-adenosylmethionine. Hepatic MAT activity falls in chronic liver diseases, and mice lacking Mat1a are predisposed to liver injury and develop ... ...

Abstract	Unlabelled: Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the biosynthesis of S-adenosylmethionine. Hepatic MAT activity falls in chronic liver diseases, and mice lacking Mat1a are predisposed to liver injury and develop hepatocellular carcinoma (HCC) spontaneously by 18 months. The current work examined the hypothesis that liver cancer stem cells contribute to HCC in this model. Livers from 6- and 18-month-old Mat1a-knockout (KO) mice and their wild-type (WT) littermates were fractionated and isolated by flow cytometry. CD45- nonparenchymal (NP) cells were cultured using liver stem cell conditions. Cells were analyzed by real-time PCR and fluorescent immunohistochemistry (FIHC). Tumor formation was assessed by injecting 1 x 10(6) CD133+CD49f+ cells intraperitoneally into immune-deficient mice. The proportion of CD49f+ and CD133+ cells in the CD45-NP fraction increased 4.5- to 5.5-fold from 6 to 18 months in KO mice but not in their WT littermates. Compared to CD49f- cells from old KO mice, CD49f+ cells from the same animals had a markedly increased expression of several oncogenes. CD133+ cells with CD49f coexpression were selected in vitro and exhibited rapid growth, with the expression of biliary cytokeratins, alpha-fetoprotein, and c-Met by FIHC. Clonal expansion of single CD133+CD49f+ cells revealed maintenance of bipotency. After CD133+CD49f+ cells were injected into immune-deficient mice, 3 of the 8 mice developed tumors of liver epithelial cells after 6-8 weeks. Conclusion: Mat1a(-/-) mice have expansion of liver stem cells as they age. These cells have increased expression of several oncogenes and are tumorigenic in vivo. This is the first demonstration of adult liver stem cells possessing tumorigenic potential without the use of a carcinogen or manipulation of tumor-suppressor or oncogene expression.
MeSH term(s)	AC133 Antigen ; Aging/physiology ; Animals ; Antigens, CD/metabolism ; Biomarkers/metabolism ; Carcinoma, Hepatocellular/metabolism ; Cell Proliferation ; Flow Cytometry ; Glycoproteins/metabolism ; Integrin alpha6/metabolism ; Leukocyte Common Antigens/metabolism ; Liver Neoplasms/metabolism ; Methionine Adenosyltransferase/deficiency ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Neoplastic Stem Cells/physiology ; Oncogene Proteins/metabolism ; Peptides/metabolism
Chemical Substances	AC133 Antigen ; Antigens, CD ; Biomarkers ; Glycoproteins ; Integrin alpha6 ; Oncogene Proteins ; Peptides ; Prom1 protein, mouse ; Mat1a protein, mouse (EC 2.5.1.6) ; Methionine Adenosyltransferase (EC 2.5.1.6) ; Leukocyte Common Antigens (EC 3.1.3.48) ; Ptprc protein, mouse (EC 3.1.3.48)
Language	English
Publishing date	2008-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604603-4
ISSN	1527-3350 ; 0270-9139
ISSN (online)	1527-3350
ISSN	0270-9139
DOI	10.1002/hep.22141
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1660: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: A CD133-expressing murine liver oval cell population with bilineage potential.

Rountree, C Bart / Barsky, Lora / Ge, Shundi / Zhu, Judy / Senadheera, Shantha / Crooks, Gay M

Stem cells (Dayton, Ohio)

2007 Volume 25, Issue 10, Page(s) 2419–2429

Abstract: Although oval cells are postulated to be adult liver stem cells, a well-defined phenotype of a bipotent liver stem cell remains elusive. The heterogeneity of cells within the oval cell fraction has hindered lineage potential studies. Our goal was to ... ...

Abstract	Although oval cells are postulated to be adult liver stem cells, a well-defined phenotype of a bipotent liver stem cell remains elusive. The heterogeneity of cells within the oval cell fraction has hindered lineage potential studies. Our goal was to identify an enriched population of bipotent oval cells using a combination of flow cytometry and single cell gene expression in conjunction with lineage-specific liver injury models. Expression of cell surface markers on nonparenchymal, nonhematopoietic (CD45-) cells were characterized. Cell populations were isolated by flow cytometry for gene expression studies. 3,5-Diethoxycarbonyl-1,4-dihydrocollidine toxic injury induced cell cycling and expansion specifically in the subpopulation of oval cells in the periportal zone that express CD133. CD133+CD45- cells expressed hepatoblast and stem cell-associated genes, and single cells coexpressed both hepatocyte and cholangiocyte-associated genes, indicating bilineage potential. CD133+CD45- cells proliferated in response to liver injury. Following toxic hepatocyte damage, CD133+CD45- cells demonstrated upregulated expression of the hepatocyte gene Albumin. In contrast, toxic cholangiocyte injury resulted in upregulation of the cholangiocyte gene Ck19. After 21-28 days in culture, CD133+CD45- cells continued to generate cells of both hepatocyte and cholangiocyte lineages. Thus, CD133 expression identifies a population of oval cells in adult murine liver with the gene expression profile and function of primitive, bipotent liver stem cells. In response to lineage-specific injury, these cells demonstrate a lineage-appropriate genetic response. Disclosure of potential conflicts of interest is found at the end of this article.
MeSH term(s)	1-Naphthylisothiocyanate/toxicity ; AC133 Antigen ; Animals ; Antigens, CD/analysis ; Biomarkers ; Bone Marrow Transplantation ; Carbon Tetrachloride Poisoning/pathology ; Cell Division ; Cell Lineage ; Cells, Cultured/metabolism ; Chemical and Drug Induced Liver Injury/pathology ; Dicarbethoxydihydrocollidine/toxicity ; Gene Expression Profiling ; Glycoproteins/analysis ; Immunophenotyping ; Liver/cytology ; Liver Regeneration/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Mice, Transgenic ; Peptides/analysis ; Radiation Chimera
Chemical Substances	AC133 Antigen ; Antigens, CD ; Biomarkers ; Glycoproteins ; Peptides ; Prom1 protein, mouse ; 1-Naphthylisothiocyanate (551-06-4) ; Dicarbethoxydihydrocollidine (632-93-9)
Language	English
Publishing date	2007-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1143556-2
ISSN	1549-4918 ; 1066-5099
ISSN (online)	1549-4918
ISSN	1066-5099
DOI	10.1634/stemcells.2007-0176
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1894: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito