Formation of functional tissue from transplanted adrenocortical cells expressing telomerase reverse transcriptase

• Published in: Nature biotechnology 2000-01, Vol.18 (1), p.39-42
• Main Authors: Hornsby, Peter J, Thomas, Michael, Yang, Lianqing
• Format: Article
• Language: English
• Subjects: Adrenal Cortex - cytology; Adrenal Cortex - enzymology; Adrenal Cortex - metabolism; adrenocortical cells; Agriculture; Animals; Antigens; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Cattle; Cell cycle; Cell division; Cell Division - genetics; Cell Transformation, Neoplastic - genetics; Cell Transplantation; Cells, Cultured; Cellular Senescence - genetics; Chimera - genetics; Clone Cells - metabolism; Cloning; corticosterone; cortisone; Cytomegalovirus; Deoxyribonucleic acid; DNA; DNA Probes - genetics; Fundamental and applied biological sciences. Psychology; Genetic Vectors - genetics; Health. Pharmaceutical industry; Humans; Hydrocortisone - blood; Industrial applications and implications. Economical aspects; Kidney; Kidneys; Life Sciences; Mice; Mice, SCID; Miscellaneous; Plasmids; Proteins; Senescence; Simian virus 40; Telomerase; Telomerase - genetics; Telomerase - metabolism; Telomere - enzymology; Telomere - genetics; Telomere - metabolism; tissue engineering; Tissues; Transfection; Transplantation, Heterologous; Transplants & implants
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/71894

We report the first use of human telomerase reverse transcriptase (hTERT) expression in experimental xenotransplantation. Previously, we showed that bovine adrenocortical cells can be transplanted into severe combined immunodeficient (SCID) mice, and that these cells form functional tissue that replaces the animals' own adrenal glands. We cotransfected primary bovine adrenocortical cells with plasmids encoding hTERT, SV40 T antigen, neo, and green fluorescent protein. These clones do not undergo loss of telomeric DNA and appear to be immortalized. Two clones were transplanted beneath the kidney capsule of SCID mice. Animals that received cell transplants survived indefinitely despite adrenalectomy. The mouse glucocorticoid, corticosterone, was replaced by the bovine glucocorticoid, cortisol, in the plasma of these animals. The tissue formed from the transplanted cells resembled that formed by transplantation of cells that were not genetically modified and was similar to normal bovine adrenal cortex. The proliferation rate in tissues formed from these clones was low and there were no indications of malignant transformation.