Effects of exogenous peripheral-blood-derived endothelial progenitor cells or unfractionated bone-marrow-derived cells on neointimal formation and inflammation in cholesterol-fed, balloon-denuded, and radiated iliac arteries of inbred rabbits

Waksman, Ron; Baffour, Richard; Pakala, Rajbabu; Scheinowitz, Mickey; Hellinga, David; Seabron, Rufus; Chan, Rosanna; Kolodgie, Frank; Virmani, Renu

doi:10.1016/j.carrev.2009.02.001

« Previous Next »Cardiovascular Revascularization Medicine
Volume 10, Issue 2 , Pages 110-116, April 2009

Effects of exogenous peripheral-blood-derived endothelial progenitor cells or unfractionated bone-marrow-derived cells on neointimal formation and inflammation in cholesterol-fed, balloon-denuded, and radiated iliac arteries of inbred rabbits

Ron Waksman
- Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA
- Corresponding author. Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington, DC 20010, USA.
Richard Baffour
- Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA
Rajbabu Pakala
- Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA
Mickey Scheinowitz
- Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA
David Hellinga
- Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA
Rufus Seabron
- Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA
Rosanna Chan
- Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA
Frank Kolodgie
- CV Path, International Registry of Pathology, Gaithersburg, MD, USA
Renu Virmani
- CV Path, International Registry of Pathology, Gaithersburg, MD, USA

Received 3 February 2009; accepted 3 February 2009.

Abstract

Background

Injection of bone marrow cells (BMC) and endothelial progenitor cells (EPC) or application of stem-cell-mobilizing factors has been associated both with reduction or exacerbation of atherosclerosis and with unstable plaque phenotype. The discrepancies may reflect the cell type, dosing, duration, and route of administration of cells in these studies. The aim of this study was to determine the effects of peripheral-blood-derived endothelial progenitor cells (PBEPC) or unfractionated BMC obtained from inbred siblings on neointimal formation and inflammation in cholesterol-fed, balloon-denuded, and radiated rabbit iliac arteries.

Methods

Rabbits were fed a 1.0% cholesterol diet for 14 days, followed by endothelial denudation in both iliac arteries, and continued on a 0.15% cholesterol diet. On day 42, denuded areas were radiated, and animals were randomized. The first group received PBEPC (n=5), the second group received BMC (n=4), and the third group received heparinized (20 IU) saline (Control; n=3). PBEPC were characterized by flow cytometry. Cells (5×10⁶) or saline was administered twice through the ear vein: the first time at 1 h after radiation and the second time at 2 weeks after radiation. Four weeks after radiation, the animals were sacrificed, and arterial segments were processed for morphometry.

Results

Administration of BMC or PBEPC from inbred siblings had no adverse effect. Lumen area (0.93±0.53 mm²), neointimal area (0.65±0.29 mm²), percent stenosis (44±21), and macrophage score (0.6±0.3) in controls were similar to those in cell-treated groups.