Abstract
As pigs are currently the preferred species for organ xenotransplantation, initial experience in liver xenotransplantation with wild-type (WT) pigs, advances in the development of genetically modified pigs, and recent studies using livers from them are reviewed. The xenotransplantation of livers from pigs transgenic for the human complement regulatory protein (CRP) CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/- additionally transgenic for the CRP CD46 (GTKO/CD46 pigs) is associated with the survival of approximately 1 week. Satisfactory hepatic function has been documented, lending support to the concept that the pig liver might provide a bridge to allotransplantation. However, although significant features of rejection have not been documented, the development of an immediate thrombocytopenia after graft reperfusion is problematic and leads to spontaneous hemorrhage within the body cavities, native organs, and graft. Current studies are being directed to understand the factors causing the activation, aggregation, or phagocytosis of platelets, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes, and Kupffer cells. If this problem can be resolved, a clinical trial of pig liver xenotransplantation as a bridge to allotransplantation may be both feasible and justified.
| Original language | English |
|---|---|
| Pages (from-to) | 158-167 |
| Number of pages | 10 |
| Journal | Xenotransplantation |
| Volume | 18 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 2011 |
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Keywords
- α1,3-galactosyltransferase gene knockout
- hCD46
- liver
- liver failure, acute
- non-human primate
- pig
- xenotransplantation
ASJC Scopus subject areas
- Transplantation
- Immunology
Cite this
Clinical pig liver xenotransplantation : How far do we have to go? / Ekser, Burcin; Gridelli, Bruno; Veroux, Massimiliano; Cooper, David K C.
In: Xenotransplantation, Vol. 18, No. 3, 05.2011, p. 158-167.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical pig liver xenotransplantation
T2 - How far do we have to go?
AU - Ekser, Burcin
AU - Gridelli, Bruno
AU - Veroux, Massimiliano
AU - Cooper, David K C
PY - 2011/5
Y1 - 2011/5
N2 - As pigs are currently the preferred species for organ xenotransplantation, initial experience in liver xenotransplantation with wild-type (WT) pigs, advances in the development of genetically modified pigs, and recent studies using livers from them are reviewed. The xenotransplantation of livers from pigs transgenic for the human complement regulatory protein (CRP) CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/- additionally transgenic for the CRP CD46 (GTKO/CD46 pigs) is associated with the survival of approximately 1 week. Satisfactory hepatic function has been documented, lending support to the concept that the pig liver might provide a bridge to allotransplantation. However, although significant features of rejection have not been documented, the development of an immediate thrombocytopenia after graft reperfusion is problematic and leads to spontaneous hemorrhage within the body cavities, native organs, and graft. Current studies are being directed to understand the factors causing the activation, aggregation, or phagocytosis of platelets, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes, and Kupffer cells. If this problem can be resolved, a clinical trial of pig liver xenotransplantation as a bridge to allotransplantation may be both feasible and justified.
AB - As pigs are currently the preferred species for organ xenotransplantation, initial experience in liver xenotransplantation with wild-type (WT) pigs, advances in the development of genetically modified pigs, and recent studies using livers from them are reviewed. The xenotransplantation of livers from pigs transgenic for the human complement regulatory protein (CRP) CD55 or from α1,3-galactosyltransferase gene-knockout pigs+/- additionally transgenic for the CRP CD46 (GTKO/CD46 pigs) is associated with the survival of approximately 1 week. Satisfactory hepatic function has been documented, lending support to the concept that the pig liver might provide a bridge to allotransplantation. However, although significant features of rejection have not been documented, the development of an immediate thrombocytopenia after graft reperfusion is problematic and leads to spontaneous hemorrhage within the body cavities, native organs, and graft. Current studies are being directed to understand the factors causing the activation, aggregation, or phagocytosis of platelets, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes, and Kupffer cells. If this problem can be resolved, a clinical trial of pig liver xenotransplantation as a bridge to allotransplantation may be both feasible and justified.
KW - α1,3-galactosyltransferase gene knockout
KW - hCD46
KW - liver
KW - liver failure, acute
KW - non-human primate
KW - pig
KW - xenotransplantation
UR - http://www.scopus.com/inward/record.url?scp=79959750277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959750277&partnerID=8YFLogxK
U2 - 10.1111/j.1399-3089.2011.00642.x
DO - 10.1111/j.1399-3089.2011.00642.x
M3 - Article
C2 - 21696445
AN - SCOPUS:79959750277
VL - 18
SP - 158
EP - 167
JO - Xenotransplantation
JF - Xenotransplantation
SN - 0908-665X
IS - 3
ER -