BACKGROUND: In recent years, interest has been revived in the possibility of transplanting organs into humans from a phylogenetically disparate species such as the pig (xenotransplantation). Such discordant xenografts, however, are subject to hyperacute rejection (HAR) and activation of host complement plays a major role in this rejection. This problem may be solved through the use of transgenic technology by providing the grafted tissue with molecules that down-regulate the action of host complement. RESULTS: Transgenesis with a yeast artificial chromosome (YAC) was used to produce transgenic mice with the complete genomic gene of the human complement regulator membrane cofactor protein (MCP). Transgenic mice were obtained that exhibit full regulation of MCP as normally observed in humans. Hearts from these mice were shown to be significantly protected from HAR caused by human serum in an in vivo experimental procedure. CONCLUSIONS: We conclude that MCP can protect discordant xenografts from HAR caused by human serum and that transgenic mice can be used effectively as in vivo models for the study of the role of human complement regulatory molecules in xenotransplantation.
BACKGROUND: In recent years, interest has been revived in the possibility of transplanting organs into humans from a phylogenetically disparate species such as the pig (xenotransplantation). Such discordant xenografts, however, are subject to hyperacute rejection (HAR) and activation of host complement plays a major role in this rejection. This problem may be solved through the use of transgenic technology by providing the grafted tissue with molecules that down-regulate the action of host complement. RESULTS: Transgenesis with a yeast artificial chromosome (YAC) was used to produce transgenic mice with the complete genomic gene of the human complement regulator membrane cofactor protein (MCP). Transgenic mice were obtained that exhibit full regulation of MCP as normally observed in humans. Hearts from these mice were shown to be significantly protected from HAR caused by human serum in an in vivo experimental procedure. CONCLUSIONS: We conclude that MCP can protect discordant xenografts from HAR caused by human serum and that transgenic mice can be used effectively as in vivo models for the study of the role of human complement regulatory molecules in xenotransplantation.
Authors: O J A E Ophorst; K Radosević; M J E Havenga; M G Pau; L Holterman; B Berkhout; J Goudsmit; M Tsuji Journal: Infect Immun Date: 2006-01 Impact factor: 3.441
Authors: B Roscic-Mrkic; R A Schwendener; B Odermatt; A Zuniga; J Pavlovic; M A Billeter; R Cattaneo Journal: J Virol Date: 2001-04 Impact factor: 5.103
Authors: Amando Zuniga; Mathias Liniger; Teldja Neige Azzouz Morin; René R Marty; Marian Wiegand; Orhan Ilter; Sara Weibel; Martin A Billeter; Marlyse C Knuchel; Hussein Y Naim Journal: Hum Vaccin Immunother Date: 2013-01-16 Impact factor: 3.452