Immobilized DNA aptamers used as potent attractors for porcine endothelial precursor cells.

Because of their insufficient biocompatibility and high thrombogenicity, small diameter artificial vascular prostheses still do not show a satisfactory patency rate. In vitro endothelialization of artificial grafts before implantation has been established experimentally years ago, but, this procedure is extremely time consuming and expensive. This study deals with the coating of graft surfaces with capture molecules (aptamers) for circulating endothelial progenitor cells (EPCs), mimicking a prohoming substrate to fish out EPCs from the bloodstream after implantation and to create an autologous functional endothelium. Using the SELEX technology, aptamers with a high affinity to EPCs were identified, isolated, and grafted onto polymeric discs using a blood compatible star-PEG coating. A porcine in vitro model that demonstrates the specific adhesion of EPCs and their differentiation into vital endothelial-like cells within 10 days in cell culture is presented. We suggest that the rapid adhesion of EPCs to aptamer-coated implants could be useful to promote endothelial wound healing and to prevent increased neointimal hyperplasia. We hypothesize that future in vivo self-endothelialization of blood contacting implants by homing factor mimetic capture molecules for EPCs may bring revolutionary new perspectives towards clinical applications of stem cell and tissue engineering strategies.

[1]  Volker A Erdmann,et al.  Selection of RNA aptamers to the Alzheimer's disease amyloid peptide. , 2002, Biochemical and biophysical research communications.

[2]  B. Sullenger,et al.  Aptamers: an emerging class of therapeutics. , 2005, Annual review of medicine.

[3]  S. Jayasena.  Aptamers: an emerging class of molecules that rival antibodies in diagnostics. , 1999, Clinical chemistry.

[4]  V. Prasad,et al.  Potent Inhibition of Human Immunodeficiency Virus Type 1 Replication by Template Analog Reverse Transcriptase Inhibitors Derived by SELEX (Systematic Evolution of Ligands by Exponential Enrichment) , 2002, Journal of Virology.

[5]  Martina Rimmele,et al.  Nucleic Acid Aptamers as Tools and Drugs: Recent Developments , 2003, Chembiochem : a European journal of chemical biology.

[6]  L. Gold,et al.  Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. , 1990, Science.

[7]  C. Claussen,et al.  Prophylaxis of Restenosis With 186Re-Labeled Stents in a Rabbit Model , 2001, Circulation.

[8]  F. Cicuttini,et al.  Characterization of CD3 4+HLA-DR-CD38+ and CD34+HLA-DR-CD38-progenitor cells from human umbilical cord blood , 1994 .

[9]  Yoshikazu Nakamura,et al.  Selection of RNA aptamers against recombinant transforming growth factor-beta type III receptor displayed on cell surface. , 2006, Biochimie.

[10]  H. Schluesener,et al.  Systematic Evolution of a DNA Aptamer Binding to Rat Brain Tumor Microvessels , 2001, The Journal of Biological Chemistry.

[11]  D. Klee,et al.  Blood cell and plasma protein repellent properties of Star-PEG-modified surfaces , 2006, Journal of biomaterials science. Polymer edition.

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

[13]  J. Isner,et al.  Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[14]  J. Szostak,et al.  In vitro selection of RNA molecules that bind specific ligands , 1990, Nature.

[15]  F. Liu,et al.  In vitro selection of novel RNA ligands that bind human cytomegalovirus and block viral infection. , 2000, RNA.

[16]  M. Famulok,et al.  Nucleic acid aptamers-from selection in vitro to applications in vivo. , 2000, Accounts of chemical research.

[17]  H. Crijns,et al.  Silicon-carbide coated coronary stents have low platelet and leukocyte adhesion during platelet activation. , 1999, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[18]  Gerard Pasterkamp,et al.  Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenous in Vivo Cell Seeding with Anti-cd34 Antibodies Successfully Accelerates in Vivo Cell Seeding with Anti-cd34 Antibodies Successfully Accelerates Endothelialization but Stimulates Intimal Hyperplasia in Porcine Arteriovenou , 2022 .

[19]  Y. Ikeda,et al.  Endothelial Differentiation Potential of Human Monocyte‐Derived Multipotential Cells , 2006, Stem cells.

[20]  M. Kutryk,et al.  Endothelial progenitor cells: new hope for a broken heart. , 2003, Circulation.

[21]  M. Hristov,et al.  Endothelial progenitor cells: mobilization, differentiation, and homing. , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[22]  P. Tornvall,et al.  Clinical and angiographic follow‐up after coronary drug‐eluting and bare metal stent implantation. Do drug‐eluting stents hold the promise? , 2006, Journal of internal medicine.

[23]  J. Isner,et al.  Therapeutic Potential of Ex Vivo Expanded Endothelial Progenitor Cells for Myocardial Ischemia , 2001, Circulation.

[24]  D. Guyer,et al.  Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease , 2006, Nature Reviews Drug Discovery.

[25]  Chandler Ab.  In vitro thrombotic coagulation of the blood; a method for producing a thrombus. , 1958 .

[26]  S. Silber.  Capturing circulating endothelial progenitor cells: a new concept tested in the HEALING studies. , 2006, Minerva Cardioangiologica : a Journal on Cardiovascular Pathophysiology, Clinical Medicine and Therapy.

[27]  H. Wendel,et al.  Aptamer‐based capture molecules as a novel coating strategy to promote cell adhesion , 2005, Journal of cellular and molecular medicine.

[28]  Bertrand Tavitian,et al.  Nucleic acid aptamers in cancer medicine , 2002, FEBS letters.

[29]  Michael V Sefton,et al.  Biomaterial-associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes. , 2004, Biomaterials.

[30]  J. Isner,et al.  Endothelial recovery: the next target in restenosis prevention. , 2003, Circulation.

[31]  E D Verrier,et al.  Endothelial cell injury in cardiovascular surgery: the systemic inflammatory response. , 1997, The Annals of thoracic surgery.

[32]  F Joffre,et al.  Intravascular stents to prevent occlusion and restenosis after transluminal angioplasty. , 1987, The New England journal of medicine.