scholarly journals Radiologic Differences between Bone Marrow Stromal and Hematopoietic Progenitor Cell Lines from Fanconi Anemia (Fancd2–/–) Mice

2014 ◽  
Vol 181 (1) ◽  
pp. 76 ◽  
Author(s):  
Hebist Berhane ◽  
Michael W. Epperly ◽  
Julie Goff ◽  
Ronny Kalash ◽  
Shaonan Cao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Fanconi Anemia ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor

scholarly journals Growth hormone exerts hematopoietic growth-promoting effects in vivo and partially counteracts the myelosuppressive effects of azidothymidine

Blood ◽  
1992 ◽  
Vol 80 (6) ◽  
pp. 1443-1447
Author(s):  
WJ Murphy ◽  
G Tsarfaty ◽  
DL Longo
Keyword(s):  
Immune Deficiency ◽  
Bone Marrow ◽  
Growth Hormone ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Cell Content ◽  
Cell Counts ◽  
Growth Promoting

Recombinant human growth hormone (rhGH) was administered to mice to determine its effect on hematopoiesis. BALB/c mice and mice with severe combined immune deficiency (SCID), which lack T cells and B cells, were administered intraperitoneal injections of rhGH for 7 days. Upon analysis, both strains of mice exhibited an increase in splenic and bone marrow hematopoietic progenitor cell content and cellularity, indicating that rhGH can act as a hematopoietic growth factor. C57BL/6 mice were then placed on azidothymidine (AZT). AZT is a reverse transcriptase inhibitor currently used as a treatment for acquired immune deficiency syndrome (AIDS), but which also produces significant myelotoxic effects. Treatment of mice with rhGH partially counteracted the myelosuppressive properties of AZT. Bone marrow cellularity, hematocrit values, white blood cell counts, and splenic hematopoietic progenitor cell content were all significantly increased if rhGH (20 micrograms injected intraperitoneally every other day) was concurrently administered with AZT. Administration of ovine GH (ovGH), which, unlike rhGH, has no effect on murine prolactin receptors, also prevented the erythroid-suppressive effects of AZT in mice, but had no significant effect on granulocyte counts. Thus, the effects of GH are mediated at least in part through GH receptors in vivo. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of ovGH resulted in an increase in splenic hematopoietic progenitor cells. No significant pathologic effects were observed in mice receiving either repeated rhGH or ovGH injections. Thus, GH exerts significant direct hematopoietic growth-promoting effects in vivo and may be of potential clinical use to promote hematopoiesis in the face of myelotoxic therapy.

Functional Correction of Fanconi Anemia Group A Hematopoietic Cells by Retroviral Gene Transfer

Blood ◽  
1997 ◽  
Vol 90 (9) ◽  
pp. 3296-3303 ◽  
Author(s):  
Kai-Ling Fu ◽  
Jerome R. Lo Ten Foe ◽  
Hans Joenje ◽  
Kathleen W. Rao ◽  
Johnson M. Liu ◽  
...  
Keyword(s):  
Cell Growth ◽  
Progenitor Cells ◽  
Fanconi Anemia ◽  
Progenitor Cell ◽  
Hematopoietic Cells ◽  
Retroviral Vectors ◽  
Retroviral Vector ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Increased Risk

Abstract Fanconi anemia (FA) is an autosomal recessive genetic disorder characterized by a variety of physical anomalies, bone marrow failure, and an increased risk for malignancy. FA cells exhibit chromosomal instability and are hypersensitive to DNA cross-linking agents such as mitomycin C (MMC). FA is a clinically heterogeneous disorder and can be functionally divided into at least five different complementation groups (A-E). We previously described the use of a retroviral vector expressing the FAC cDNA in the complementation of mutant hematopoietic cells from FA-C patients. This vector is currently being tested in a clinical trial of ex vivo hematopoietic progenitor cell transduction. The FA-A group accounts for over 65% of all FA cases, and the FAA cDNA was recently identified by both expression and positional cloning techniques. We report here the transduction and phenotypic correction of lymphoblastoid cell lines from four unrelated FA-A patients, using two amphotropic FAA retroviral vectors. Expression of the FAA transgene was adequate to normalize cell growth, cell-cycle kinetics, and chromosomal breakage in the presence of MMC. We then analyzed the effect of retroviral vector transduction on hematopoietic progenitor cell growth. After FAA transduction of mutant progenitor cells, either colony number or colony size increased in the presence of MMC. In addition, FAA but not FAC retroviral transduction markedly improved colony growth of progenitor cells derived from an unclassified FA patient. FAA retroviral vectors should be useful for both complementation studies and clinical trials of gene transduction.

Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After High-Dose Therapy With Autologous Hematopoietic Progenitor-Cell Support for Lymphoid Malignancies

2000 ◽  
Vol 18 (5) ◽  
pp. 947-947 ◽  
Author(s):  
Ivana N. M. Micallef ◽  
Debra M. Lillington ◽  
John Apostolidis ◽  
John A. L. Amess ◽  
Michael Neat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cell ◽  
Myelogenous Leukemia ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Progenitor ◽  
Acute Myelogenous ◽  
Cell Support

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q−, 15 had −7/7q−, seven had −18/18q−, seven had −13/13q−, and four had −20/20q−. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P = .009) and older age (P = .02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P = .05 and .07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.

scholarly journals Targeted gene transfer to human hematopoietic progenitor cell lines through the c-kit receptor

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 472-478 ◽  
Author(s):  
P Schwarzenberger ◽  
SE Spence ◽  
JM Gooya ◽  
D Michiel ◽  
DT Curiel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Cell Lines ◽  
Progenitor Cell ◽  
Gene Transfection ◽  
Luciferase Reporter ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor ◽  
Hematopoietic Stem ◽  
Covalently Linked

In this report, we describe a novel gene therapy approach for hematopoietic stem/progenitor cells using a specific receptor-mediated gene transfection procedure to target c-kit+ cell lines. The vector consists of plasmid DNA containing a luciferase reporter gene that is condensed by electrostatic forces with polylysine (PL) covalently linked to streptavidin (binds biotinylated ligand) and PL covalently linked to adenovirus (AD; to achieve endosomal lysis) with the final addition of biotinylated steel factor (SLF-biotin). Targeted transfection of growth factor-dependent hematopoietic progenitor cell lines that express c-kit showed specific luciferase gene expression over cell lines that did not express c-kit. This effect was dependent on the dose of SLF-biotin and was competed by excess SLF or with monoclonal antibodies that recognize c-kit and block the binding of SLF to its receptor. Maximum transfection efficiency (> 90%) requires a 2- hour incubation period of the vector with the cells, and maximum gene expression occurred 30 hours later. Removal of the endosomalytic agent, AD, from the vector resulted in the loss of gene expression. Vector targeting was versatile and could be changed by the addition of other biotinylated ligands. In principle, this vector should be broadly applicable to deliver genes to hematopoietic stem/progenitor cells in vitro and in vivo.

Long-term “in vitro” proliferating mouse hematopoietic progenitor cell lines

2010 ◽  
Vol 130 (1-2) ◽  
pp. 32-35 ◽  
Author(s):  
Patricia Vegh ◽  
Jana Winckler ◽  
Fritz Melchers
Keyword(s):  
Cell Lines ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
Hematopoietic Progenitor
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