Pig islet xenograft rejection in a mouse model with an established human immune system.
Xenotransplantation
; 15(2): 129-35, 2008.
Article
em En
| MEDLINE
| ID: mdl-18447886
ABSTRACT
BACKGROUND:
Xenotransplantation from pigs provides a potential solution to the severe shortage of human pancreata, but strong immunological rejection prevents its clinical application. A better understanding of the human immune response to pig islets would help develop effective strategies for preventing graft rejection.METHODS:
We assessed pig islet rejection by human immune cells in humanized mice with a functional human immune system. Humanized mice were prepared by transplantation of human fetal thymus/liver tissues and CD34(+) fetal liver cells into immunodeficient mice. Islet xenograft survival/rejection was determined by histological analysis of the grafts and measurement of porcine C-peptide in the sera of the recipients.RESULTS:
In untreated humanized mice, adult pig islets were completely rejected by 4 weeks. These mice showed no detectable porcine C-peptide in the sera, and severe intra-graft infiltration by human T cells, macrophages, and B cells, as well as deposition of human antibodies. Pig islet rejection was prevented by human T-cell depletion prior to islet xenotransplantation. Islet xenografts harvested from T-cell-depleted humanized mice were functional, and showed no human cell infiltration or antibody deposition.CONCLUSIONS:
Pig islet rejection in humanized mice is largely T-cell-dependent, which is consistent with previous observations in non-human primates. These humanized mice provide a useful model for the study of human xenoimmune responses in vivo.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Suínos
/
Transplante Heterólogo
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Transplante das Ilhotas Pancreáticas
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Modelos Animais
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Rejeição de Enxerto
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Sistema Imunitário
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article