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Related Experiment Videos

Urokinase expression in transduced endothelial cells

L E Townsend1, J L Glover, K T Trevor

  • 1Department of Surgery, William Beaumont Hospital, Royal Oak, Michigan, USA.

The American Surgeon
|August 1, 1996
PubMed
Summary

Genetically modified endothelial cells can release more urokinase, a clot-dissolving agent. This approach may enhance the performance of prosthetic grafts by improving their resistance to blood clots.

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Area of Science:

  • Biomedical Engineering
  • Vascular Biology
  • Gene Therapy

Background:

  • Endothelial cell function is crucial for prosthetic graft patency.
  • Thromboresistance can be improved by enhancing the release of lytic agents.
  • Urokinase is a key thrombolytic agent involved in fibrinolysis.

Purpose of the Study:

  • To evaluate the expression of urokinase in endothelial cells transduced with a human preprourokinase gene.
  • To assess the potential of genetically modified endothelial cells for improving prosthetic graft performance.

Main Methods:

  • Endothelial cells were harvested from canine veins and cultured.
  • Cells were transduced using a retroviral vector carrying the urokinase gene.
  • Transduced cells were selected using G418, and urokinase expression/activity was measured.

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Main Results:

  • Transduced cells showed significant measurable concentrations of human urokinase (0.15 ng/mL/hr/10(6) cells).
  • Overall urokinase enzyme activity was significantly higher in transduced cells compared to controls.
  • Control cells showed no measurable human urokinase concentration.

Conclusions:

  • Endothelial cells can be successfully transduced to express and release urokinase.
  • This gene modification increases the availability of a crucial thrombolytic agent.
  • Lining prosthetic grafts with these modified cells holds promise for enhanced thromboresistance and patency.