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Related Experiment Videos

Human endothelial cell life extension by telomerase expression.

J Yang1, E Chang, A M Cherry

  • 1Department of Dermatology, Stanford University School of Medicine, Stanford, California 94305-5486, USA.

The Journal of Biological Chemistry
|September 3, 1999
PubMed
Summary

Introducing human telomerase reverse transcriptase (hTERT) into endothelial cells bypasses replicative senescence. These extended-life vascular cells retain normal function, angiogenic potential, and resistance to apoptosis, making them promising for vascular therapies.

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Area of Science:

  • Cell Biology
  • Vascular Biology
  • Biotechnology

Background:

  • Normal somatic cells, including endothelial cells, undergo replicative senescence, a limited number of cell divisions.
  • Expression of human telomerase reverse transcriptase (hTERT) has previously extended the lifespan of other cell types without inducing cancerous transformation.
  • Endothelial cells are crucial for vascular health and tissue regeneration.

Purpose of the Study:

  • To investigate whether hTERT expression can extend the lifespan of human endothelial cells.
  • To determine if hTERT-expressing endothelial cells retain their differentiated and functional characteristics.
  • To assess the potential of hTERT-modified endothelial cells for therapeutic applications.

Main Methods:

  • Introduction of hTERT into large vessel and microvascular endothelial cells.

Related Experiment Videos

  • Assessment of cell proliferation, senescence bypass, and lifespan extension.
  • Evaluation of differentiated and functional phenotype, including angiogenic potential in vitro.
  • Karyotype analysis and assessment for transformed phenotype.
  • Apoptosis resistance assays under various conditions.

    • Main Results:

    • hTERT expression enabled both large vessel and microvascular endothelial cells to bypass replicative senescence.
    • Life-extended endothelial cells maintained their differentiated and functional phenotype and in vitro angiogenic potential.
    • hTERT-expressing microvascular endothelial cells exhibited a normal karyotype and did not display a transformed phenotype.
    • hTERT-expressing endothelial cells showed increased resistance to apoptosis induction compared to senescent parental cells.

    Conclusions:

    • hTERT expression is a viable strategy to extend the lifespan of human endothelial cells.
    • These hTERT-modified endothelial cells retain critical functional properties, including angiogenic potential.
    • The enhanced resistance to apoptosis and normal phenotype of hTERT-expressing endothelial cells make them highly suitable for vascular transplantation and gene therapy delivery systems.