Cell-based therapy facilitates venous thrombus resolution.
Endothelial progenitor cells (EPC) are involved in many healing processes in cardiovascular diseases and can be found in spontaneously resolving venous thrombi. The purpose of the present study was to investigate whether the therapeutic administration of EPC might enhance the resolution of venous thrombi. For this purpose, venous thrombosis was induced in the infrarenal inferior vena cava (IVC) in 28 athymic nude rats. Culture expanded EPC derived from human peripheral blood mononuclear cells were injected intravenously two and four days after thrombus induction. Recanalisation of the IVC and thrombus organisation were assessed by laser Doppler measurements of the blood flow and immunohistochemical detection of endothelialised luminal structures in the thrombus. EPC transplantation resulted in significantly enhanced thrombus neovascularisation (capillary density: 186.6 +/- 26.7/HPF vs. 78 +/- 12.3/HPF, p<0.01; area covered by capillaries: 8.9 +/- 1.7 microm(2) vs. 2.5 +/- 1.3 microm(2), p<0.01) and was accompanied by a substantial increase in intra-thrombus blood flow (perfusion ratio: 0.7 +/- 0.07 vs. 0.3 +/- 0.08, p<0.02). These results were paralleled by augmented macrophage recruitment into resolving thrombi in the animals treated with EPC (39.4 +/- 4.7/HPF vs. 11.6 +/- 1.9/HPF, p<0.01). Our data suggest that EPC transplantation might be of clinical value to facilitate venous thrombus resolution in cases where current therapeutic options have limited success.
Santo
Stefano Di
SD
Division of Vascular Medicine, Swiss Cardiovascular Center, Inselspital, Bern University Hospital, Freiburgstrasse, CH-3010 Bern, Switzerland.
Tepper
Oren M
OM
von Ballmoos
Moritz Wyler
MW
Diehm
Nicolas
N
Völzmann
Jan
J
Baumgartner
Iris
I
Kalka
Christoph
C
D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D018919:Neovascularization, Physiologic; D051381:Rats; D011923:Rats, Nude; D033581:Stem Cell Transplantation; D020246:Venous Thrombosis / Q000473:pathology / Q000601:surgery / Q000628:therapy*