Prospects for insulin delivery by ex-vivo somatic cell gene therapy

1999 ◽  
Vol 77 (1) ◽  
pp. 244-249 ◽  
Author(s):  
C. J. Bailey ◽  
Emma L. Davies ◽  
Kevin Docherty
Keyword(s):  
Gene Therapy ◽  
Somatic Cell ◽  
Ex Vivo ◽  
Insulin Delivery ◽  
Somatic Cell Gene Therapy ◽  
Cell Gene

Insulin delivery by somatic cell gene therapy

1993 ◽  
Vol 11 (3) ◽  
pp. 335-341 ◽  
Author(s):  
C Stewart ◽  
N A Taylor ◽  
K Docherty ◽  
C J Bailey
Keyword(s):  
Gene Therapy ◽  
Somatic Cell ◽  
Insulin Release ◽  
Human Insulin ◽  
Outer Region ◽  
Insulin Delivery ◽  
Control Group ◽  
C Peptide ◽  
Somatic Cell Gene Therapy ◽  
Cell Gene

ABSTRACT The feasibility of somatic cell gene therapy as a method of insulin delivery has been studied in mice. Murine pituitary AtT20 cells were transfected with a human preproinsulin DNA in a plasmid containing a metallothionein promoter and a gene conferring resistance to the antibiotic G418. The AtT20MtIns-1·4 clone of cells was selected because of its higher insulin-releasing activity compared with other clones. After culturing for 24 h in Dulbecco's medium containing 10 mM glucose, the AtT20MtIns-1·4 cells released human insulin at about 5 ng/106 cells per 24 h. Insulin release was not significantly altered by raised concentrations of glucose, potassium or calcium, but insulin release was increased by 20 mm arginine, 5 mm isomethylbutylxanthine and 90 μm zinc. AtT20MtIns-1·4 cells (2 × 106) were implanted intraperitoneally into non-diabetic athymic nude (nu/nu) mice, and the mice were made diabetic by injection of streptozotocin after 7 days. Release of human insulin in vivo was assessed using a specific plasma human C-peptide assay. Human C-peptide concentrations were maintained at about 01 pmol/ml throughout the 29 days of the study. The development of streptozotocin-induced hyperglycaemia was delayed in recipients of the cells releasing human insulin, compared with a control group receiving an implant of non-transfected cells. At autopsy the implanted AtT20MtIns-1·4 cells in each recipient had formed a tumour-like aggregation, with an outer region of insulin-containing cells. The study suggests that somatic cell gene therapy offers a feasible approach to insulin delivery.

Insulin-releasing pituitary cells as a model for somatic cell gene therapy in diabetes mellitus

1994 ◽  
Vol 142 (2) ◽  
pp. 339-343 ◽  
Author(s):  
C Stewart ◽  
N A Taylor ◽  
I C Green ◽  
K Docherty ◽  
C J Bailey
Keyword(s):  
Diabetes Mellitus ◽  
Gene Therapy ◽  
Somatic Cell ◽  
Human Insulin ◽  
Insulin Delivery ◽  
Pituitary Cells ◽  
C Peptide ◽  
Metallothionein Promoter ◽  
Somatic Cell Gene Therapy ◽  
Cell Gene

Abstract Insulin delivery by somatic cell gene therapy was evaluated using murine pituitary AtT20MtIns-1.4 cells. These cells have been stably transfected to release human insulin by the introduction of a recombinant plasmid bearing a human preproinsulin cDNA under the control of a zinc-sensitive metallothionein promoter. 6 × 107 AtT20MtIns-1.4 cells were implanted subcutaneously into streptozotocin-diabetic mice immunosuppressed with cyclosporin A. Release of human insulin was assessed using a specific plasma human C-peptide assay. On days 1 and 2 after implantation human C-peptide concentrations were about 0·02 pmol/ml. Consumption of zinc sulphate solution (500 mg/l) as drinking fluid for days 3–5 increased plasma human C-peptide concentrations to 0·11 ±0·01 pmol/ml (mean±s.e.m.), n=11, P<0·01, and concentrations declined when zinc was discontinued. The extent of hyperglycaemia was slightly lower (P<0·05) than in a group implanted with non-transfected AtT20 cells. The study was terminated after 9 days, and tumour-like aggregations of implanted cells were identified at autopsy. These comprised a large necrotic core with insulin-containing cells at the periphery. The study provides support for the view that somatic cell gene therapy offers a potential approach to insulin delivery in diabetes mellitus. Journal of Endocrinology (1994) 142, 339–343

Optimizing Ribozymes for Somatic Cell Gene Therapy

1998 ◽  
Vol 6 (1) ◽  
pp. 78-83 ◽  
Author(s):  
Andrea D. Branch ◽  
Paul E. Klotman
Keyword(s):  
Gene Therapy ◽  
Somatic Cell ◽  
Somatic Cell Gene Therapy ◽  
Cell Gene

Development of Methods for Somatic Cell Gene Therapy Directed Against Viral Diseases, Using Retroviral Vectors Carrying the Murine or Human Interferon-β Coding Sequence: Establishment of the Antiviral State in Human Cells

1993 ◽  
Vol 4 (5) ◽  
pp. 567-577 ◽  
Author(s):  
Evelyne Lauret ◽  
Isabelle Riviere ◽  
Véronique Rousseau ◽  
Vincent Vieillard ◽  
Jaqueline De Maeyer-Guignard ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Somatic Cell ◽  
Retroviral Vectors ◽  
Human Cells ◽  
Viral Diseases ◽  
Human Interferon ◽  
Interferon Β ◽  
Coding Sequence ◽  
Somatic Cell Gene Therapy ◽  
Cell Gene

scholarly journals A murine model for B-lymphocyte somatic cell gene therapy.

1994 ◽  
Vol 91 (19) ◽  
pp. 8875-8879 ◽  
Author(s):  
N. Sutkowski ◽  
M. L. Kuo ◽  
A. Varela-Echavarria ◽  
J. P. Dougherty ◽  
Y. Ron
Keyword(s):  
Gene Therapy ◽  
Somatic Cell ◽  
Murine Model ◽  
B Lymphocyte ◽  
Somatic Cell Gene Therapy ◽  
Cell Gene

Epidermal Keratinocytes: Opportunities and Applications in Somatic Cell Gene Therapy

2018 ◽  
pp. 73-90
Author(s):  
Brian J. Aneskievich ◽  
Anthony G. Letai ◽  
Elaine Fuchs
Keyword(s):  
Gene Therapy ◽  
Somatic Cell ◽  
Epidermal Keratinocytes ◽  
Somatic Cell Gene Therapy ◽  
Cell Gene

Transkaryotic implantation and the somatic cell gene therapy of diabetes

1990 ◽  
Vol 3 (1) ◽  
pp. 93
Author(s):  
Richard F. Selden ◽  
Mary Ellen Rowe ◽  
Howard M. Goodman
Keyword(s):  
Gene Therapy ◽  
Somatic Cell ◽  
Somatic Cell Gene Therapy ◽  
Cell Gene
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