Delivery of stem cells to porcine arterial wall with echogenic liposomes conjugated to antibodies against CD34 and intercellular adhesion molecule-1.
In atherosclerosis, the loss of vascular stem cells via apoptosis impairs the capacity of the vascular wall to repair or regenerate the tissue damaged by atherogenic factors. Recruitment of exogenous stem cells to the plaque tissue may repopulate vascular cells and help repair the arterial tissue. Ultrasound-enhanced liposomal targeting may provide a feasible method for stem cell delivery into atheroma. Bifunctional echogenic immunoliposomes (BF-ELIP) were generated by covalently coupling two antibodies to liposomes; the first one specific for CD34 antigens on the surface of stem cells and the second directed against the intercellular adhesion molecule-1 (ICAM-1) antigens on the inflammatory endothelium covering atheroma. CD34+ stem cells from adult bone marrow were incubated on the ICAM-1-expressing endothelium of the aorta of swine fed high cholesterol diets, which was preloaded with BF-ELIP. Significantly increased stem cell adherence and penetration were detected in particular in the aortic segments treated with 1 MHz low-amplitude continuous wave ultrasound. Fluorescence and scanning electron microscopy confirmed the presence of BF-ELIP-bound CD34+ cells in the intimal compartment of the atheromatous arterial wall. Ultrasound treatment increased the number of endothelial cell progenitors migrating into the intima. Thus, under ultrasound enhancement, BF-ELIP bound CD34+ stem cells selectively bind to the ICAM-1 expressing endothelium of atherosclerotic lesions.
Herbst
Stephanie M
SM
Division of Cardiology, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Klegerman
Melvin E
ME
Kim
Hyunggun
H
Qi
Jiangbo
J
Shelat
Harnath
H
Wassler
Michael
M
Moody
Melanie R
MR
Yang
Chen-Min
CM
Ge
Xinyi
X
Zou
Yuejiao
Y
Kopechek
Jonathan A
JA
Clubb
Fred J
FJ
Kraemer
Duane C
DC
Huang
Shaoling
S
Holland
Christy K
CK
McPherson
David D
DD
Geng
Yong-Jian
YJ
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D018952:Antigens, CD34 / Q000276:immunology / Q000378:metabolism; D001158:Arteries / Q000166:cytology* / Q000000981:diagnostic imaging; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002448:Cell Adhesion; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D008081:Liposomes; D008297:Male; D013552:Swine; D013556:Swine, Miniature; D014463:Ultrasonography
D000906:Antibodies; D018952:Antigens, CD34; D008081:Liposomes; D018799:Intercellular Adhesion Molecule-1