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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2761-2766.
Prepublished online as a Blood First Edition Paper on July 8, 2004; DOI 10.1182/blood-2003-10-3614.


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Submitted October 23, 2003
Accepted June 10, 2004

Apoptotic Bodies from Endothelial Cells Enhance the Number and Initiate the Differentiation of Human Endothelial Progenitor Cells in vitro

Mihail Hristov*, Wolfgang Erl, Stefan Linder, and Peter C Weber

Institute for Prevention of Cardiovascular Diseases, Ludwig-Maximilians-Universitat, Munich, Germany

* Corresponding author; email: mhristov{at}med.uni-muenchen.de.

Endothelial progenitor cells (EPC) play a role in the repair of ischemic or injured tissue. Because endothelial injury can be associated with apoptosis, we have investigated whether apoptotic bodies from mature endothelial cells (EC) may affect EPC growth and differentiation in vitro. A 24 h incubation of isolated human EPC with apoptotic bodies-rich medium (ABRM) from EC lead to a significant increase in the number of spindle-shaped attached cells. EPC were characterized by DiI-Ac-LDL/lectin staining and measurement of CD34 and kinase insert domain receptor (KDR) expression. The treatment with ABRM resulted in a twofold increase of DiI-Ac-LDL/lectin positive cells and upregulation of CD34 (22.2 ± 1.8% vs. 13.1 ± 2.7%, P< 0.05) and KDR (49.4 ± 12.3% vs. 18.8 ± 7.1%, P< 0.05). Fluorescence and confocal laser microscopy demonstrated the uptake of apoptotic bodies by the EPC. Apoptotic bodies-depleted medium had no effect, whereas the incubation with suspension of apoptotic bodies induced effects similar to those of ABRM. Our results suggest that apoptotic bodies from EC are taken up by EPC, increasing their number and differentiation state. Such a mechanism may facilitate the repair of injured endothelium and may represent a new signaling pathway between progenitor and damaged somatic cells.


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