Endoluminal reconstruction of the arterial wall with endothelial cell/glue matrix reduces restenosis in an atherosclerotic rabbit
Nicholas Kipshidze, MD, PhD, FACC¶,
James J. Ferguson, III, MD, FACC ,
Michael H. Keelan, Jr., MD, FACC*,
Harry Sahota, MD ,
Richard Komorowski, MD*,
Latha Raja Shankar, MD*,
Paramjith S. Chawla, MD*,
Christian C. Haudenschild, MD||,
Victor Nikolaychik, MD and
Jeffrey W. Moses, MD, FACC¶
* Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Milwaukee Heart Project, Milwaukee, Wisconsin, USA
Good Samaritan Hospital, Los Angeles, California, USA
Texas Heart Institute, Houston, Texas, USA
|| JH Holland Laboratory, American Red Cross, Rockville, Maryland, USA
¶ Lenox Hill Heart and Vascular Institute of New York, and Cardiovascular Research Foundation, New York, New York, USA
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Figure 1 Percentage of cells attached to the vessel wall after endothelial cell/glue application and exposition to blood flow. Efficiency of attachment was calculated from intensity of fluorescent stain PKm-26 extracted from the transplanted cells.
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Figure 2 Fluorescent micrograph of fluorescent labeled transplanted endothelial cells 4 h after vascular reconstruction. Cross-section of rabbit iliac artery. Note the new endothelial layer. L = lumen; M = media; NE = new endothelial cell/glue layer.
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Figure 3 Scanning electron micrograph of rabbit iliac artery 4 h after treatment. Distal segment of the rabbit iliac artery treated with endothelial cell/glue matrix. (Original magnification x 400.) Note transplanted endothelial cells within fibrin matrix on the surface of the iliac artery. The endothelial cells are in the process of attachment. In the areas not covered by glue/cell matrix, the subendothelium is exposed and debris is seen. C = untreated segment; NE = new endothelial cell/glue matrix.
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Figure 4 Movat’s stain. (A) Iliac artery of cholesterol-fed rabbit 60 days after balloon injury and local saline (control) application. Cross-section shows representative fibrocellular hyperplasia with focal macrophage/foam cell accumulation in the core. Waviness of both remaining internal and external laminae is suggestive of a remodeling process leading to shrinkage. (B) Contralateral iliac artery of the same animal after balloon injury and local application of glue. Cross-section shows comparable initial mechanical injury with fibrocellular hyperplasia without significant foam cell accumulation. Little inflammation and no angiogenesis are seen, but the tunica adventitia displays some reinforcing collagenous thickening in the upper left quadrant. (C) and (D) Iliac arteries from another cholesterol fed animal 60 days after procedure. On both iliac there is neointima around the entire circumference, but the internal elastic lamina is intact, and the original tunica media shows intimal cell loss and little compression, indicating that in these positions the initial injuries were present, symmetric and comparable. (C) The segment treated with endothelial cell seeding shows a concentric lesion with the fibrocellular intimal hyperplasia. (D) Local treatment with glue/cell reconstruction results in a minimal fibrocellular hyperplasia with little variation in thickness mostly due to the previous neointima. (A) to (D) Movat stain all taken with a digital camera at the same magnification and further processed with photofinish 4. L = lumen; M = media; N = neointima.
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Figure 5 (A) Example of a severe lesion from another animal showing a significant breaking of the internal elastic lamina, the media and external elastic lamina, with very extensive neointimal hyperplasia and formation of a lipid rich core 60 days after treatment with endothelial cell seeding procedure. (B) Contralateral artery from the same animal with comparable level of injury. The intima in this glue/cell treated segment is moderate and hypercellular in nature.
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