ENDOTHELIAL CELL LINE'S LATEST USE:LINING ARTERY REPLACEMENTS
By David N. LeffScience Editor
Blood coursing through a healthy artery owes its smoothpassage to the super-smooth layer of endothelial cells that linethe vessel's inner surface. When this lumen is blocked byatherosclerotic plaque building up from its intimal layer,bypass surgery may replace the plugged-up stretch of arterywith a vein from the patient's leg or a synthetic tubular meshof knitted Dacron.
All too often these spare parts get clogged in turn bythrombosis or fibrosis. Lining grafts with cultured humanendothelial cells could prevent such setbacks. A recentinvention developed at the Centers for Disease Control (CDC) inAtlanta and nearby Emory University pictures off-the-shelf (orrather, out-of-the-freezer) lengths of Dacron mesh pre-coatedwith transgenic microvascular endothelial cells, ready for thecardiac surgeon to warm up and sew in.
Via a recent Federal Register announcement, CDC is offeringnon-exclusive licenses to industry for commercial and researchuse of this patent-pending immortalized cell line. The originalpatent application, No. 07/679,674, dates from April 4, 1991.
Endothelial cells do other jobs in the body besides providingthe bloodstream with a friction-free raceway. They are, amongmany other things, critical components of wound healing,inflammation, angiogenesis, leukocyte trafficking and tumormetastasis. Cell biologists researching these fields arehampered by the devilish difficulty of isolating and culturinghuman endothelial cells.
The pending patent's principal inventor, Edwin Ades, and histeam at CDC's Biological Products Branch, which he heads, tookthe endothelial cell line initially established from half-a-dozenhuman foreskins. They transfected these cells with the geneencoding the large T antigen of simian virus 40. As promoter,they used the Rous sarcoma virus' long terminal repeat. Unlikethe native cells, which die out in culture after, at most, 10generations, this genetically engineered line has already passed100 replications in the past 500 or so days and is still goingstrong.
"This is the first-ever human, long-term, microvascular,endothelial cell line," Ades told BioWorld. "These immortalizedcell lines are mycoplasma-free, virus-free, HIV-negative, andthey provide a ready source of human endothelial cells for suchcommercial research purposes as factors that induceendothelial mitosis, substrates for the screening ofpharmaceutical agents and toxicological studies for thecosmetics and pharmaceutical industries, for instancecholesterol."
Now, to the above, add ready-to-wear coronary bypassprostheses, their lumens coated with immortal humanmicrovascular endothelial cells. This application was developedjointly with CDC by cardiologist Keith Robinson of EmoryUniversity School of Medicine.
In in vitro tests, cultures of the transfected cells were seededonto small segments of surgical Dacron mesh and onto stents(cylinders used something like splints, inserted internally toimmobilize the sutured seams of attached replacements). Aftertwo weeks of static culture the cells confluently coated thefabric at least one cell thick and retained their integrity afterfreezing.
Current bypass procedure, Ades pointed out, obtainsendothelial cells from the patient's own spare vein or adiposetissue. "These harvesting procedures require additional orextended operating-room time and expense," he said.
So far, Ades' group has not reported trying the cell-coatingsystem in live animals. Nor have they yet investigated itspossible down-sides, which Emory's Keith Robinson cites.
"It is conceivable that after implantation in vivo, continuedproliferation of the immortalized human endothelial cells mightactually contribute to intimal thickening and graft failure," saidRobinson. Moreover, "its antigenic potential remains unknown.Therefore, chronic implantation studies in animal modelsshould begin."
Presumably, would-be licensure companies or institutionswould carry forward such continued R&D. But, emphasizesCarol Lavrich, the contract specialist at OTT which is handlingthis invention, non-exclusive licenses are also available forother potential uses of the immortal cells. Her number is (301)496-7735.
(c) 1997 American Health Consultants. All rights reserved.