Guided tissue regeneration: porcine matrix does not transmit PERV.

OBJECTIVE For cardiovascular tissue engineering, acellularized scaffolds of porcine matrices have been successfully used. However, the possibility of porcine endogenous retrovirus (PERV) transmission remains debatable. In this study, we investigated whether acellularized porcine vascular scaffolds cause cross-species transmission of PERV in a xenogenic model. METHODS Porcine pulmonary arteries were acellularized and implanted into sheep in orthotopic position (n=6). Cardiopulmonary bypass support was used for all operations. Blood samples were collected regularly up to 6 months after the operation, and cellular components were tested for PERV infection by PCR and RT-PCR. Grafts were explanted 6 and 12 months after implantation. Tissue samples were characterized by histology and electron microscopy and tested for PERV sequences. RESULTS All animals survived the procedure and follow up until explantation of the grafts. PERV DNA was detectable in acellularized scaffolds of porcine matrices. Acellular porcine pulmonary arteries scaffolds were repopulated in vivo by autologous cells of the host, leading to a vessel consisting of all cellular components of the vessel wall. No PERV sequences were detectable neither in all tested peripheral blood samples nor in tissue samples of in vivo recellularized grafts up to 6 months after implantation. Electron microscopy revealed no signs of graft infection by retrovirus. CONCLUSIONS Guided tissue regeneration of acellularized vascular porcine matrix scaffolds leads to structured vessels up to one year without risk of PERV transmisson.

[1]  H. Alexander,et al.  Development and characterization of tissue-engineered aortic valves. , 2001, Tissue engineering.

[2]  F J Schoen,et al.  Tissue-engineered valved conduits in the pulmonary circulation. , 2000, The Journal of thoracic and cardiovascular surgery.

[3]  M. Schwartz,et al.  The extracellular matrix as a cell survival factor. , 1993, Molecular biology of the cell.

[4]  H. Mertsching,et al.  In vivo model for cross-species porcine endogenous retrovirus transmission using tissue engineered pulmonary arteries. , 2003, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[5]  Frederick J Schoen,et al.  Cardiovascular tissue engineering. , 2002, Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology.

[6]  A. Schmiedl,et al.  The surface to volume ratio of mitochondria, a suitable parameter for evaluating mitochondrial swelling , 1990, Virchows Archiv A.

[7]  R. T. Lee,et al.  Integrin-mediated collagen matrix reorganization by cultured human vascular smooth muscle cells. , 1995, Circulation research.

[8]  A Haverich,et al.  Tissue Engineering of Pulmonary Heart Valves on Allogenic Acellular Matrix Conduits: In Vivo Restoration of Valve Tissue , 2000, Circulation.

[9]  Robert Langer,et al.  Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation , 1999, The Lancet.

[10]  E. Baer,et al.  Deformation in tendon collagen. , 1980, Symposia of the Society for Experimental Biology.

[11]  W. Heneine,et al.  No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts , 1998, The Lancet.

[12]  Gustav Steinhoff,et al.  Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells , 1998, The Lancet.

[13]  M. Karnovsky,et al.  A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron-microscopy , 1965 .

[14]  Frederick J. Schoen,et al.  Early In Vivo Experience With Tissue-Engineered Trileaflet Heart Valves , 2000, Circulation.

[15]  Timothy M. Rose,et al.  Type C Retrovirus Released from Porcine Primary Peripheral Blood Mononuclear Cells Infects Human Cells , 1998, Journal of Virology.

[16]  D. Hoffman,et al.  Transesophageal echocardiography for the evaluation of mitral valve prostheses in the weanling sheep. , 1991, ASAIO transactions.

[17]  A Haverich,et al.  Heart valves from pigs and the porcine endogenous retrovirus: experimental and clinical data to assess the probability of porcine endogenous retrovirus infection in human subjects. , 2001, The Journal of thoracic and cardiovascular surgery.

[18]  D. White,et al.  The generation of transgenic pigs as potential organ donors for humans , 1995, Nature Medicine.

[19]  Yasuhiro Takeuchi,et al.  Infection of human cells by an endogenous retrovirus of pigs , 1997, Nature Medicine.

[20]  F. Nistal,et al.  Comparative study of calcification in the T6-treated and standard Hancock-I porcine xenografts: experimental study in weanling sheep. , 1986, The Thoracic and cardiovascular surgeon.

[21]  U A Stock,et al.  Tissue engineering: current state and prospects. , 2001, Annual review of medicine.

[22]  F J Schoen,et al.  Functional Living Trileaflet Heart Valves Grown In Vitro , 2000, Circulation.

[23]  H. Mertsching,et al.  Investigations on biological safety and immunologic aspects of chimeric bioartificial vessels in xenotransplantation. , 2000, Transplantation proceedings.

[24]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[25]  W. Heneine,et al.  Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group. , 1999, Science.

[26]  I Vesely,et al.  Natural preload of aortic valve leaflet components during glutaraldehyde fixation: effects on tissue mechanics. , 1993, Journal of biomechanics.

[27]  H. Erickson,et al.  Endothelial cells adhere to the RGD domain and the fibrinogen-like terminal knob of tenascin. , 1993, Journal of cell science.

[28]  H. Mertsching,et al.  Construction of Autologous Human Heart Valves Based on an Acellular Allograft Matrix , 2002, Circulation.

[29]  D. Cheresh,et al.  Recognition of distinct adhesive sites on fibrinogen by related integrins on platelets and endothelial cells , 1989, Cell.