Autologous endothelial progenitor cells transplantation promoting endothelial recovery in mice

Transplantation of endothelial progenitor cells (EPCs) restores endothelial function. The present study was designed to determine the effect of autologous EPCs transplantation on the regeneration of endothelium in mice. Mice splenectomy was performed 14 days before carotid artery injury, and mononuclear cells were isolated and cultured in endothelial growth media for 7 days. EPCs were confirmed by immunostaining (CD31, endothelial nitric oxide synthase (eNOS) and double positive for 1,1’dioctadecyl‐3,3,3’,3‐tetramethylindocarbocyanine (DiI)‐low‐density lipoprotein and ulex europaeus agglutinin (UEA)). Cell counts and fluorescence‐activated cell sorting for stem cell marker were performed. 1 × 106 4‐,6‐Diamidino‐2‐phenylindole‐ labeled EPCs or saline were injected through tail vein after wire injury. Two weeks after transplantation, cell tracking and immunohistochemical staining showed homing and incorporation of labeled EPCs in injury artery. Administration of EPCs enhanced reendothelialization (P < 0.05) after 1 week and inhibition of neointima formation at 3 weeks compared with that of saline (P < 0.05, n = 6). These data demonstrate that delivery of autologous EPCs is associated with accelerated reendothelialization and reduced neointimal formation. Thus, delivery of autologous EPCs represents an important vasculoprotective approach to attenuate the response to acute vascular injury.

[1]  A M Zeiher,et al.  HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway. , 2001, The Journal of clinical investigation.

[2]  U. Laufs,et al.  Intravenous Transfusion of Endothelial Progenitor Cells Reduces Neointima Formation After Vascular Injury , 2003, Circulation research.

[3]  G. Nickenig,et al.  Improvement of Endothelial Function by Systemic Transfusion of Vascular Progenitor Cells , 2006, Circulation research.

[4]  Leslie A. Smith,et al.  Transplantation of Circulating Endothelial Progenitor Cells Restores Endothelial Function of Denuded Rabbit Carotid Arteries , 2004, Stroke.

[5]  J. Wang,et al.  Surgical injury induces the mobilization of endothelial progenitor cells. , 2004, Surgery.

[6]  R. Mulligan,et al.  Isolation and Transplantation of Autologous Circulating Endothelial Cells Into Denuded Vessels and Prosthetic Grafts: Implications for Cell-Based Vascular Therapy , 2003, Circulation.

[7]  I. Barshack,et al.  Transfer of endothelial progenitor cells improves myocardial performance in rats with dilated cardiomyopathy induced following experimental myocarditis. , 2005, Journal of molecular and cellular cardiology.

[8]  Winfried Brenner,et al.  Assessment of the Tissue Distribution of Transplanted Human Endothelial Progenitor Cells by Radioactive Labeling , 2003, Circulation.

[9]  M. C. Lin,et al.  Heart and lung disease in engineered mice , 1995, Nature Medicine.

[10]  M. Goligorsky,et al.  Dynamics of mobilization and homing of endothelial progenitor cells after acute renal ischemia: modulation by ischemic preconditioning. , 2006, American journal of physiology. Renal physiology.

[11]  Christie M. Orschell,et al.  Peripheral Blood “Endothelial Progenitor Cells” Are Derived From Monocyte/Macrophages and Secrete Angiogenic Growth Factors , 2003, Circulation.

[12]  S. Achatz,et al.  Vascular gene delivery of anticoagulants by transplantation of retrovirally-transduced endothelial progenitor cells. , 2003, Cardiovascular research.

[13]  H. Miller,et al.  Transfer of Endothelial Progenitor and Bone Marrow Cells Influences Atherosclerotic Plaque Size and Composition in Apolipoprotein E Knockout Mice , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[14]  A. Mangi,et al.  Enhanced Inhibition of Neointimal Hyperplasia by Genetically Engineered Endothelial Progenitor Cells , 2004, Circulation.

[15]  R. Vile,et al.  Autologous Culture-Modified Mononuclear Cells Confer Vascular Protection After Arterial Injury , 2003, Circulation.

[16]  M. Endres,et al.  Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis. , 2003, Circulation.

[17]  C. Heeschen,et al.  Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. , 2003, Blood.

[18]  J. Dick,et al.  Hematopoietic stem cell and progenitor defects in Sca-1/Ly-6A-null mice. , 2003, Blood.

[19]  J. Isner,et al.  The biology of restenosis. , 1997, Progress in cardiovascular diseases.

[20]  M. Reidy,et al.  Mouse model of arterial injury. , 1993, Circulation research.

[21]  U. Dirnagl,et al.  Estrogen Increases Bone Marrow‐Derived Endothelial Progenitor Cell Production and Diminishes Neointima Formation , 2003, Circulation.