Efficacy of cationic liposome-mediated gene transfer to mesangial cells in vitro and in vivo

2001 ◽  
Vol 79 (4) ◽  
pp. 184-189 ◽  
Author(s):  
Henning Madry ◽  
Regina Reszka ◽  
Jürgen Bohlender ◽  
Jürgen Wagner
Keyword(s):  
Gene Transfer ◽  
Mesangial Cells ◽  
Cationic Liposome

Cationic Liposome-Mediated Gene Transfer to Tumor Cells In Vitro and In Vivo

2003 ◽  
pp. 329-338 ◽  
Author(s):  
Kyonghee Son ◽  
Frank Sorgi ◽  
Xiang Gao ◽  
Leaf Huang
Keyword(s):  
Gene Transfer ◽  
Tumor Cells ◽  
Cationic Liposome

scholarly journals An approach for the analysis of relapse and marrow reconstitution after autologous marrow transplantation using retrovirus-mediated gene transfer

Blood ◽  
1992 ◽  
Vol 79 (10) ◽  
pp. 2694-2700 ◽  
Author(s):  
DR Rill ◽  
RC Moen ◽  
M Buschle ◽  
C Bartholomew ◽  
NK Foreman ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Marrow Transplantation ◽  
Residual Disease ◽  
Marker Gene ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Disease Recurrence ◽  
Malignant Cells

Abstract Autologous bone marrow transplantation (ABMT) is widely used as treatment for malignant disease. Although the major cause of treatment failure is relapse, it is unknown if this arises entirely because of residual disease in the patient or whether contaminating cells in the rescuing marrow contribute. Attempts to purge marrow of its putative residual malignant cells may delay hematopoietic reconstitution and are of uncertain efficacy. We now describe how retrovirus-mediated gene transfer may be used to elucidate the source of relapse after ABMT for acute myeloid leukemia and to evaluate the efficacy of purging. Clonogenic myeloid leukemic blast cells in patient marrow can be transduced with the NeoR gene-containing helper-free retrovirus, LNL6, with an efficacy of 0% to 23.5% (mean, 10.5%). Transduced colonies grow in selective media and the presence of the marker gene can be confirmed in individual malignant colonies by polymerase chain reaction. If such malignant cells remain in harvested “remission” marrow, they will therefore be marked after exposure to LNL6. Detection of the marker gene in the malignant cells present at any later relapse would be firm evidence that residual disease contributed to disease recurrence, and would permit rapid subsequent evaluation of purging techniques. The technique also marks normal marrow progenitors from patients with acute myeloblastic leukemia. These colony-forming cells can be detected in long-term marrow cultures at a frequency of 1% to 18% for up to 10 weeks after exposure to the vector. Animal models and analysis of probability tables both suggest that these levels of marking in vitro are sufficient to provide information about the mechanisms of relapse and the biology of marrow regeneration in vivo. These preclinical data form part of the basis for current clinical studies of gene transfer into marrow before ABMT.

scholarly journals Gene transfer of multidrug resistance into a factor-dependent human hematopoietic progenitor cell line: in vivo model for genetically transferred chemoprotection

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2723-2731 ◽  
Author(s):  
P Schwarzenberger ◽  
S Spence ◽  
N Lohrey ◽  
T Kmiecik ◽  
DL Longo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Gene Transfer ◽  
Hematopoietic Progenitor Cells ◽  
Mdr1 Gene ◽  
In Vivo Model ◽  
Hematopoietic Progenitor ◽  
Human Dna

To develop a rapid preclinical in vivo model to study gene transfer into human hematopoietic progenitor cells, MO-7e cells (CD-34+, c-kit+) were infected with multidrug resistance (MDR1)-containing retroviruses and then transplanted into nonobese diabetic severe combined immunodeficient mice (NOD SCID). MO-7e cells infected with a retrovirus encoding the human MDR1 cDNA showed integration, transcription, and expression of the transfered MDR1 gene. This resulted in a 20-fold increase in the resistance of MO-7e cells to paclitaxel in vitro. The expression of the MDR1 gene product was stable over a 6-month period in vitro without selection in colchicine. MO-7e and MDR1-infected MO-7e cells were transplanted into NOD SCID mice to determine whether MDR1 could confer drug resistance in vivo. A sensitive polymerase chain reaction method specific for human sequences was developed to quantitate the level of human cell engraftment in NOD SCID bone marrow (BM) cells. The percentage of human DNA in BM cells from MO-7e- transplanted mice was 10.9% and decreased to 0.7% in mice treated with paclitaxel. The percentage of human DNA in infected-MO-7e transplanted mice was 7.6% and that level was unchanged in mice treated with paclitaxel. These results show that expression of the MDR1 gene in human hematopoietic progenitor cells can confer functional drug resistance in an in vivo model.

Highly efficient cell-mediated gene transfer using non-viral vectors and FuGene™6: in vitro and in vivo studies

2000 ◽  
Vol 57 (8) ◽  
pp. 1326-1333 ◽  
Author(s):  
I. Hellgren* ◽  
V. Drvota ◽  
R. Pieper ◽  
S. Enoksson ◽  
P. Blomberg ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Viral Vectors ◽  
In Vivo Studies ◽  
Highly Efficient

scholarly journals Insulin induces rapid and specific rearrangement of the cytoskeleton of rat mesangial cells in vitro.

1996 ◽  
Vol 44 (2) ◽  
pp. 91-101 ◽  
Author(s):  
A K Berfield ◽  
G J Raugi ◽  
C K Abrass
Keyword(s):  
Mesangial Cells ◽  
Focal Adhesions ◽  
Cytoskeletal Proteins ◽  
Direct Effects ◽  
Ligand Effects ◽  
Igf I ◽  
Induced Changes ◽  
Secondary Ligand

Mesangial cells (MCs) grown without supplemental insulin (SI-MCs) express a quiescent phenotype and extracellular matrix (ECM) composition similar to MCs in vivo. In contrast, MCs routinely propagated in insulin (SI+MCs) are stimulated to proliferate, change their phenotype, and produce large amounts of collagens I and III. These effects of insulin may in part be mediated through cytoskeletal rearrangement. Differences in cytoskeletal arrangement were compared between SI-MCs and SI+MCs and 1 hr after addition of insulin (1 nM) or IGF-1 (100 nM) to SI-MCs. Cells were examined by light microscopy, electron microscopy, and immunostaining for specific cytoskeletal proteins and fibronectin. Insulin induced rapid rearrangement of stress fibers. Surface ruffling, actin aggregation, vimentin retraction, rearrangement of vinculin in focal adhesions, and fibronectin extraction were apparent. These direct effects of insulin on the SI-MC cytoskeleton occurred before insulin-induced changes in ECM composition. IGF-I induced cytoskeletal reorganization distinct from insulin. These observations demonstrate that insulin and IGF-I have unique effects on the MC cytoskeleton, which is turn may mediate secondary ligand effects on MCs.

P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function

2002 ◽  
Vol 82 (1) ◽  
pp. 131-185 ◽  
Author(s):  
Richard J. Roman
Keyword(s):  
Arachidonic Acid ◽  
Angiotensin Ii ◽  
Vascular Tone ◽  
Mesangial Cells ◽  
Cardiovascular Function ◽  
Tubuloglomerular Feedback ◽  
Peripheral Vasculature ◽  
Therapeutic Benefits

Recent studies have indicated that arachidonic acid is primarily metabolized by cytochrome P-450 (CYP) enzymes in the brain, lung, kidney, and peripheral vasculature to 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatrienoic acids (EETs) and that these compounds play critical roles in the regulation of renal, pulmonary, and cardiac function and vascular tone. EETs are endothelium-derived vasodilators that hyperpolarize vascular smooth muscle (VSM) cells by activating K+channels. 20-HETE is a vasoconstrictor produced in VSM cells that reduces the open-state probability of Ca2+-activated K+channels. Inhibitors of the formation of 20-HETE block the myogenic response of renal, cerebral, and skeletal muscle arterioles in vitro and autoregulation of renal and cerebral blood flow in vivo. They also block tubuloglomerular feedback responses in vivo and the vasoconstrictor response to elevations in tissue Po2both in vivo and in vitro. The formation of 20-HETE in VSM is stimulated by angiotensin II and endothelin and is inhibited by nitric oxide (NO) and carbon monoxide (CO). Blockade of the formation of 20-HETE attenuates the vascular responses to angiotensin II, endothelin, norepinephrine, NO, and CO. In the kidney, EETs and 20-HETE are produced in the proximal tubule and the thick ascending loop of Henle. They regulate Na+transport in these nephron segments. 20-HETE also contributes to the mitogenic effects of a variety of growth factors in VSM, renal epithelial, and mesangial cells. The production of EETs and 20-HETE is altered in experimental and genetic models of hypertension, diabetes, uremia, toxemia of pregnancy, and hepatorenal syndrome. Given the importance of this pathway in the control of cardiovascular function, it is likely that CYP metabolites of arachidonic acid contribute to the changes in renal function and vascular tone associated with some of these conditions and that drugs that modify the formation and/or actions of EETs and 20-HETE may have therapeutic benefits.

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