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Kazuhiko Yamada, J. Seebach, H. Dersimonian, D. Sachs (1996)
Human anti‐pig T‐cell mediated cytotoxicityXenotransplantation, 3
Sykes (1994)
Xenograft toleranceImmunol Rev, 42
D. Emery, T. Sablinski, J. Arn, C. Leguern, D. Sachs (1994)
Bone marrow culture and transduction of stem cells in a miniature swine model.Blood cells, 20 2-3
C. Smith, B. Rosengard, P. Guzzetta, K. Nakajima, D. Sachs (1991)
New approaches to transplantation tolerance.Transplantation proceedings, 23 4
M. Sykes, D. Sachs, A. Nienhuis, D. Pearson, A. Moulton, D. Bodine (1993)
Specific prolongation of skin graft survival following retroviral transduction of bone marrow with an allogeneic major histocompatibility complex gene.Transplantation, 55 1
D. Cooper, Goodwin Ah, E. Koren, R. Oriol, Malcolm Aj, Ippolito Rm, F. Neethling, Y. Ye, E. Romano, N. Zuhdi (1993)
Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man.Transplant immunology, 1 3
Guzzetta Guzzetta, Sundt Sundt, Suzuki Suzuki, Mixon Mixon, Rosengard Rosengard, Sachs Sachs (1991)
Induction of kidney transplantation tolerance across major histocompatibility complex barriers by BMT in miniature swineTransplantation, 42
P. Guzzetta, T. Sundt, Takao Suzuki, Arnold Mixon, B. Rosengard, David Sachs (1991)
Induction of kidney transplantation tolerance across major histocompatibility complex barriers by bone marrow transplantation in miniature swine.Transplantation, 51 4
T. Veromaa, S. Jalkanen, kaisa Grangors, P. Toivanen (1986)
INABILITY TO TRANSFER IMMUNE UNRESPONSIVENESS OF CHICKENS BURSECTOMIZED AT 60 HOURS OF INCUBATIONTransplantation, 42
P. Banerjee, F. Ierino, G. Kaynor, M. Giovino, T. Sablinski, D. Emery, M. Rosa, C. Leguern, D. Sachs, R. Monroy (1996)
Retrovirus-mediated transfer and expression of swine MHC class II genes in CD34+ monkey stem cells.Transplantation proceedings, 28 2
Vinay Pathak, H. Temin (1990)
Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: deletions and deletions with insertions.Proceedings of the National Academy of Sciences of the United States of America, 87
D. Bowtell, G. Johnson, A. Kelso, S. Cory (1987)
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V. Beusechem, A. Kukler, Peter HEIDTt, D. Valerio (1992)
Long-term expression of human adenosine deaminase in rhesus monkeys transplanted with retrovirus-infected bone-marrow cells.Proceedings of the National Academy of Sciences of the United States of America, 89
A. Miller, C. Buttimore (1986)
Redesign of retrovirus packaging cell lines to avoid recombination leading to helper virus productionMolecular and Cellular Biology, 6
D. Sachs, T. Sablinski (1995)
Tolerance across discordant xenogeneic barriersXenotransplantation, 2
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Lack of expression from a retroviral vector after transduction of murine hematopoietic stem cells is associated with methylation in vivo.Proceedings of the National Academy of Sciences of the United States of America, 91 7
GRAIG Smith, A. Mixon, P. Guzzetta, B. Rosengard, J. Fishbein, D. Sachs (1992)
SUCCESSFUL INDUCTION OF LONG‐TERM SPECIFIC TOLERANCE TO FULLY ALLOGENEIC RENAL ALLOGRAFTS IN MINIATURE SWINE 1Transplantation, 53
David Sachs (1994)
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Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenograftsNature, 307
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Retrovirus-mediated transfer of MHC class II cDNA into swine bone marrow cellsJ Mol Med, 42
C. Fraser, M. Sykes, R. Lee, D. Sachs, C. Leguern (1995)
Specific unresponsiveness to a retrovirally-transferred class I antigen is controlled through the helper pathway.Journal of immunology, 154 4
M. Tanaka, D. Latinne, P. Gianello, T. Sablinski, T. Lorf, M. Bailin, V. Nickeleit, R. Colvin, E. Lebowitz, M. Sykes (1994)
Xenotransplantation from pig to cynomolgus monkey: the potential for overcoming xenograft rejection through induction of chimerism.Transplantation proceedings, 26 3
J. Fishbein, B. Rosengard, P. Gianello, V. Nickeleit, P. Guzzetta, C. Smith, K. Nakajima, D. Vitiello, G. Hill, D. Sachs (1994)
Development of tolerance to class II-mismatched renal transplants after a short course of cyclosporine therapy in miniature swine.Transplantation, 57 9
L. Xu, S. Karlsson, E. Byrne, S. Kluepfel-Stahl, S. Kessler, B. Agricola, S. Sellers, M. Kirby, C. Dunbar, R. Brady (1995)
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Specific tolerance induction across a xenogeneic barrier: production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimenThe Journal of Experimental Medicine, 172
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Mixed allogeneic chimeras prepared by a non-myeloablative regimen: requirement for chimerism to maintain tolerance.Bone marrow transplantation, 9 3
T. Kawai, A. Cosimi, R. Colvin, J. Powelson, James Eason, Tomacsz Kozlowski, M. Sykes, R. Monroy, Mayumi Tanaka, D. Sachs (1995)
Mixed Allogeneic Chimerism And Renal Allograft Tolerance In Cynomolgus MonkeysTransplantation, 59
D. Kohn, K. Weinberg, J. Nolta, L. Heiss, C. Lenarsky, G. Crooks, M. Hanley, G. Annett, J. Brooks, Anthony El-Khoureiy, Kim Lawrence, S. Wells, R. Moen, J. Bastian, D. WILLIAMS-HERMAN, M. Elder, D. Wara, Thomas Bowen, M. Hershfield, C. Mullen, R. Blaese, R. Parkman (1995)
Engraftment of gene–modified umbilical cord blood cells in neonates with adenosine deaminase deficiencyNature Medicine, 1
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Expression of a swine class II gene in murine bone marrow hematopoietic cells by retroviral-mediated gene transfer.Proceedings of the National Academy of Sciences of the United States of America, 88
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Improved Retroviral Vectors for Gene Transfer and ExpressionBioTechniques, 7
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Structure of miniature swine class II DRB genes: conservation of hypervariable amino acid residues between distantly related mammalian species.Proceedings of the National Academy of Sciences of the United States of America, 87 24
B. Rosengard, C. Ojikutu, P. Guzzetta, Craig Smith, T. Sundt, S. Boorstein, G. Hill, J. Fishbein, D. Sachs (1992)
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Structure and expression of class II alpha genes in miniature swine.Journal of immunology, 149 3
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D. Sachs (1989)
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Retroviral vectors related to the myeloproliferative sarcoma virus allow efficient expression in hematopoietic stem and precursor cell lines, but retroviral infection is reduced in more primitive cells.Human gene therapy, 2 1
Abstract: Immune reactivity against products of the major histocompatibility complex (MHC) is the major barrier to allotransplantation. Conversely, sharing of MHC class II antigens I appears to be of overwhelming importance in permitting the induction of immune tolerance to vascularized organ allografts, as demonstrated previously in miniature swine. Class II antigen has also been shown to be recognized predominantly in human anti‐pig xenoreactions in vitro. To achieve tolerance in the xenogeneic pig‐to‐primate model, we are therefore investigating an approach involving retrovirus‐mediated gene therapy to transfer swine MHC (SLA) class II genes into primate primitive hematopoietic stem cells, so that swine MHC class II antigens may participate in the education of the recipient's newly developing T cell repertoire. We report here the in vitro and in vivo use of a recombinant retrovirus containing a polycistronic retroviral vector which carries swine MHC class II DRA and DRB cDNA sequences to transduce CD34+ bone marrow cells (BMC) from a cynomolgus monkey. Transduction efficiency was assessed by reverse transcriptase‐polymerase chain reaction analysis of the colony‐forming unit progenitor colonies grown in the absence of gentamycin; 55% and 24% of the progenitor colonies were determined to express the retroviral transcript at 1 week and 3 weeks post‐transduction, respectively. These in vitro studies have been extended to the transplantation of retrovirally transduced autologous stem cells into a cynomolgus monkey prepared with a non‐myeloablative conditioning regimen. Prolonged expression of SLA‐DR transcripts in monkey peripheral blood mononuclear cells (PBMC) has been documented over a 56‐week period after transplantation of retrovirus‐transduced bone marrow cells. However, we could not detect any protein expression by FACS analysis on the surface of primate PBMC or bone marrow, using a porcine SLA‐DR‐specific antibody. Engraftment of hematopoietic cells with the transduced genes was further detected in the progenitor colonies grown from the bone marrow cells harvested at 4 weeks and 25 weeks after bone marrow transplantation. Our results thus document that long‐term engraftment of retrovirally transduced hematopoietic cells can be achieved in a primate model using a non‐myeloablative preparative I regimen.
Xenotransplantation – Wiley
Published: Aug 1, 1997
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