EurekaMag.com logo
+ Site Statistics
References:
47,893,527
Abstracts:
28,296,643
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Transgenic animals in experimental xenotransplantation models: orthotopic heart transplantation in the pig-to-baboon model


, : Transgenic animals in experimental xenotransplantation models: orthotopic heart transplantation in the pig-to-baboon model. Transplantation Proceedings 39(2): 577-578

Pig organs are at risk for hyperacute and acute vascular rejection mediated by anti-pig antibodies, mainly binding to the Gal alpha(1,3)Gal epitope. Acute cellular rejection is characterized by progressive infiltration of mononuclear cells. There is an ongoing search for immunosuppressive regimens that provide adequate protection against all patterns of xenograft rejection, but have no severe impact on the condition of xenograft recipients. Herein orthotopic heart transplantations were performed from hDAF or hCD46 piglets to nonsplenectomized baboons. Basic immunosuppression consisted of tacrolimus, sirolimus, GAS914, steroids, and ATG. Group 1 received basic immunosuppression. Group 2 was additionally treated with rituximab and group 3 with half-dose cyclophosphamide. Group 4 received cyclophosphamide and an anti-HLA-DR antibody. Three baboons received GAS914 and TPC. Monitoring included the regular assessment of anti-porcine antibodies, blood counts, therapeutic drug monitoring, and graft histology. Two grafts failed due to technical mistakes. In group 1, baboons died after 1 and 9 days. In group 2, maximum survival was 30 hours. In group 3, baboons lived 20 hours, 25 days, and 14 days. Group 4 survival times were 9.5 hours, 5.5 hours, 4 days, 34 hours, and 3 days. An increase of non-Gal alpha(1,3)Gal antibodies was observed. Depositions of immunoglobulins and complement revealed a humoral rejection process. No cellular infiltration could be observed. In conclusion, suppressing cellular rejection with half-dose cyclopbosphamide together with tacrolimus and sirolimus produced longer graft survival with a good general condition. Prevention of acute xenograft rejection further needs inhibition of non-Gal alpha(1,3)Gal cytotoxicity by sufficient depression of B-cell activation.


Accession: 013275456

PMID: 17362786

DOI: 10.1016/j.transproceed.2006.12.021

Submit PDF Full Text: Here


Submit PDF Full Text

No spam - Every submission is manually reviewed

Due to poor quality, we do not accept files from Researchgate

Submitted PDF Full Texts will always be free for everyone
(We only charge for PDFs that we need to acquire)

Select a PDF file:
Close
Close

Related references

Kroshus, T.J.; Salerno, C.T.; Dalmasso, A.P.; Fodor, W.L.; Bolman, R.M., 1997: Expression of human CD59 in transgenic pig hearts extends survival in an orthotopic pig-to-baboon model of heart transplantation. Journal of Heart & Lung Transplantation 16(1): 111

Ramirez, P.; Chavez, R.; Majado, M.; Munitiz, V.; Muñoz, A.; Hernandez, Q.; Palenciano, C.; Pino-Chavez, G.; Loba, M.; Minguela, A.; Yelamos, J.; Vizcaino, A.S.; Asensi, H.; Cayuela, M.G.; Segura, B.; Marin, F.; Rubio, A.; Rios, A.; Fuente, T.; Robles, R.; Sanchez, F.; Sansano, T.; Acosta, F.; Rodriguez, J.M.; Navarro, F.; Cabezuelo, J., 2000: The porcine liver supports metabolic homeostasis in the nonhuman primate: experimental study in a model of orthotopic liver transplantation from h-DAF transgenic pig to baboon. Transplantation Proceedings 32(5): 1112-1113

Palenciano, C.G.; Segura, B.; Ramirez, P.; Acosta, F.; Sansano, T.; Chavez, R.; Majado, M.; Pino Chavez, G.; Fernandez, O.; Parrilla, P., 2001: Hemodynamical behaviour in an experimental liver xenotransplantation model from h-DAF transgenic pig to baboon. Xenotransplantation 8(Supplement 1): 71-72, August

Brandl, U.; Michel, S.; Erhardt, M.; Brenner, P.; Bittmann, I.; Rössle, M.; Baschnegger, H.; Bauer, A.; Hammer, C.; Schmoeckel, M.; Reichart, B., 2005: Administration of GAS914 in an orthotopic pig-to-baboon heart transplantation model. Background: Long-term survival of transgenic cardiac xenografts is currently limited by a form of humoral rejection named acute vascular rejection. Preformed and elicited cytotoxic antibodies against Galalpha(1,3)Gal terminating carbohydrate chain...

Palenciano, C.G.; Segura, B.; Ramirez, P.; Chavez, R.; Munitiz, V.; Cayuela, M.G.; Acosta, F.; Sansano, T.; Majado, M.; Muñoz, A.; Hernandez, O.; Pino-Chavez, G.; Loba, M.; Yelamos, J.; Gago, M.R.; Vizcaino, A.S.; Asensi, H.; Marin, F.; Rubio, A.; Fuente, T.; Rios, A.; Montoya, M.; Robles, R.; Bueno, F.S.; Rodriguez, J.M.; Navarro, F.; Cabezuelo, J.; Cozzi, E.; White, D.J.G.; Parrilla, P., 2002: Acid-base and electrolyte disturbances in an experimental model of orthotopic liver xenotransplantation from pig to baboon after graft reperfusion: differences between h-DAF livers and unmodified livers. Transplantation Proceedings 34(1): 325-326

Palenciano, C.G.; Segura, B.; Ramirez, P.; Majado, M.; Pino Chavez, G.; Hernandez, Q.; Loba, M.; Montoya, M.; Sanchez Vizcaino, A.; Parrilla, P., 2001: Acid-base and electrolyte disturbances in an experimental model of orthotopic liver xenotransplantation from pig to baboon after graft reperfusion Differences between hDAF livers and unmodified livers. Xenotransplantation 8(Supplement 1): 71, August

Munítiz, V.; Ramírez, P.; Majado, M.; Hernández, O.; Loba, M.; Montoya, M.; Chávez, R.; Muñoz, A.; Ríos, A.; Fernández, O.; Minguela, A.; Yelamos, J.; Parrilla, P., 2002: Analytical profile comparison between pig and baboon in an orthotopic liver xenotransplantation model. Transplantation Proceedings 34(1): 323-324

Munítiz, V.; Ramírez, P.; Hernández, Q.; Loba, M.; Chavez, R.; Muñoz, A.; Ríos, A.; Minguela, A.; Parrilla, P., 1999: Hematologic and hepatic function profile comparison between pig and baboon in an orthotopic liver xenotransplantation model. Transplantation Proceedings 31(6): 2641-2642

Schmoeckel, M.; Bhatti, F.N.; Zaidi, A.; Cozzi, E.; Waterworth, P.D.; Tolan, M.J.; Pino-Chavez, G.; Goddard, M.; Warner, R.G.; Langford, G.A.; Dunning, J.J.; Wallwork, J.; White, D.J., 1998: Orthotopic heart transplantation in a transgenic pig-to-primate model. Background. Previous studies demonstrated that hearts from transgenic pigs expressing human decay-accelerating factor (hDAF) were not hyperacutely rejected when transplanted heterotopically into the abdomen of cynomolgus monkeys. This study examin...

Ramírez, P.; Montoya, M.J.; Ríos, A.; García Palenciano, C.; Majado, M.; Chávez, R.; Muñoz, A.; Fernández, O.M.; Sánchez, A.; Segura, B.; Sansano, T.; Acosta, F.; Robles, R.; Sánchez, F.; Fuente, T.; Cascales, P.; González, F.; Ruiz, D.; Martínez, L.; Pons, J.A.; Rodríguez, J.I.; Yélamos, J.; Cowan, P.; d'Apice, A.; Parrilla, P., 2006: Prevention of hyperacute rejection in a model of orthotopic liver xenotransplantation from pig to baboon using polytransgenic pig livers (CD55, CD59, and H-transferase). Introduction. The search for alternative sources for transplant organs leads us to the search for animals as an inexhaustible source of organs. The objective of this study was to analyze whether livers from polytransgenic pigs expressing the human...