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

Abstract

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.

Telomeres and telomerase in hematologic neoplasia

“…Recently, Thomas et al (2000) introduced both hTERT and SV40 large T-antigen into bovine adrenal cells and showed that the modi®ed cells maintained telomeric DNA. They have demonstrated a successful transplantation of these rapidly growing engineered bovine adrenocortical cells into an adrenalectomized SCID mouse.…”

Detection of polyomaviruses and herpesviruses in human adrenal tumors

“…They have been involved in the development of several human cancers and lymphomas, but their role in human adrenal tumors has never been investigated, although experimental evidences indicate that polyomaviruses can infect and transform cells of the adrenal cortex and the adrenal medulla (Small et al, 1986;Ressetar et al, 1993Ressetar et al, , 1997Tischler et al, 1993;Servenius et al, 1994;Flaegstad et al, 1999;Thomas et al, 2000;Hornsby et al, 2002). We have recently reported the case of a patient with a large NFA, which showed histological features consistent with HCMV infection, whose presence was confirmed by detection of HCMV DNA and proteins (Pomara et al, 2006).…”

Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology

“…Recently the rst use of hTERT expression in experimental xenotransplantation has been performed (Thomas et al 2000). Primary bovine adrenocortical cells were cotransfected with plasmids encoding hTERT, SV40 T antigen, neo and green uorescent protein.…”