Endothelial progenitor cells: Characterization, in vitro expansion, and prospects for autologous cell therapy

  • D. M. Smadja
  • A. Cornet
  • J. Emmerich
  • M. Aiach
  • P. Gaussem
Article

Abstract

Injection of hematopoietic stem cells or endothelial progenitor cells (EPCs) expanded ex vivo has been shown to augment neovascularization in adult patients, but the precise origin and identity of the cell population responsible for these clinical benefits are controversial. The limited quantity of EPCs in the circulation has been the main obstacle to clinical trials. Several authors have therefore attempted to expand these cells ex vivo in order to obtain a homogeneous cell therapy product. One possible means of expanding EPCs ex vivo is to activate the thrombin receptor PAR-1 with the specific peptide SFLLRN. Indeed, PAR-1 activation promotes cell proliferation and C-X-C chemokine receptor type 4 (CXCR4) dependent migration and differentiation, with an overall angiogenic effect. This review summarizes the results and rationale of clinical trials of angiogenic therapy, the nature of EPCs, the different methods of ex vivo expansion, and current methods of quantification.

Keywords

endothelial progenitor cells clinical trials expansion thrombin receptor PAR-1 SFLLRN peptide cell therapy 

Abbreviations

AMI

acute myocardial infarction

BM-MNC

bone marrow mononuclear cell

CFU

colony-forming units

CHD

chronic heart disease

CLI

critical leg ischemia

CXCR4

C-X-C chemokine receptor type 4

EPC

endothelial progenitor cell

hTERT

human telomerase reverse transcriptase

HUVECs

human umbilical vein endothelial cells

IM

intramuscular(ly)

LDL

low-density lipoprotein

LV

left ventricular

LVEF

left ventricular ejection fraction

MAPC

multipotent adult progenitor cells

MSC

mesenchymal stem cell

PB-MNC

peripheral blood mononuclear cell

SDF-1

stromal derived factor-1

VEGF

vascular endothelial growth factor

VEGF-R2

vascular endothelial growth factor receptor 2

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Copyright information

© Springer Science + Business Media, Inc. 2007

Authors and Affiliations

  • D. M. Smadja
    • 1
    • 2
    • 4
  • A. Cornet
    • 1
    • 2
    • 4
  • J. Emmerich
    • 1
    • 3
    • 4
  • M. Aiach
    • 1
    • 2
    • 4
  • P. Gaussem
    • 1
    • 2
    • 4
    • 5
  1. 1.INSERM Unité 765ParisFrance
  2. 2.Service d’Hématologie Biologique AParisFrance
  3. 3.Service de Médecine Vasculaire, Hôpital Européen Georges Pompidou (AP-HP)ParisFrance
  4. 4.Université Paris DescartesParisFrance
  5. 5.INSERM U 765, Service d’Hématologie Biologique AHôpital Européen Georges PompidouParis Cedex 15France

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