Insulin-secreting immortalized liver cell line modified by...

Details Insulin-secreting immortalized liver cell line modified by... Insulin-secreting immortalized liver cell line modified by...

2007-12-25

2007-12-25

Woitach, Joseph (Department: 1633)

Chemistry: molecular biology and microbiology

Animal cell, per se ; composition thereof; process of...

C424S093100, C424S093210

Reexamination Certificate

active

10432592

ABSTRACT:
The present invention provides a cell line which can be substituted for β cells in human mature pancreatic islets and express insulin in a glucose-concentration dependent manner, and enables the easy obtainment of the number of cells which meets the demand. The present invention also provides a therapeutical cell preparation for treating diabetes. The cell lines of the present invention can be obtained by integrating both a nucleotide sequence encoding tamoxifen-induced Cre recombinase and a nucleotide sequence encoding insulin regulated by glucose-sensitive promoter into the chromosome in a human immortalized hepatic cell line FERM BP-7498 containing the TERT gene inserted in between a pair of LoxP sequences.

REFERENCES:
patent: 6194176 (2001-02-01), Newgard et al.
patent: 7033744 (2006-04-01), Kobayashi et al.
patent: WO 99/35245 (1999-07-01), None
patent: WO 00/04171 (2000-01-01), None
patent: WO 00/18239 (2000-04-01), None
Totsugaya, T. et al., Establishment of hTERT-immortalized human hepatocytes as a source for a hybrid bioartificial liver., Hepatology, 2001, vol. 34, No. 4, Pt. 2, pp. 305A, 531.
Lee, H.C. et al., Remission in models ofo type 1 diabetes by gene therapy using a single-chain insulin analogue., nature, 2000, vol. 408, No. 23, p. 483-8.
Cai, J. et al., Construction of a non-tumorigenic rat hepatocyte cell line for transplantation: reversal of hepatocyte immortalization by site-specific excision of the SV40 T antigen., J Hepatol, 2000, vol. 33, No. 5, p. 701-8.
Davies, E. L. et al, Glucose-sensitive insulin-secreting AtT20 cells: A model for insulin delivery by somatic cell gene therapy, Diabetologia, 1996, vol. 39, suppl. 1, pA137, 518.

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