Survival and functions of encapsulated porcine hepatocytes after allotransplantation or xenotransplantation without immunosuppression.
BACKGROUND
This study evaluated the survival and functions of encapsulated porcine hepatocytes after intraperitoneal allotransplantation and xenotransplantation without immunosuppression.


METHODS
Isolated porcine hepatocytes were encapsulated in AN 69 polymer capsules (45.10(6)/capsule) and transplanted intraperitoneally in 12 rats and 12 pigs. Fifteen, 30, and 60 days after transplantation, capsules were removed and the viability and morphology of explanted hepatocytes were examined under light and electronic microscopy. The potential to produce albumin was assessed by evaluating the level of albumin messenger RNA, using semiquantitative reverse transcription-polymerase chain reaction. 6beta-Hydroxylase activity was measured by high-performance liquid chromatography. In addition, cytochrome P450 3A proteins were detected by Western blot only in allogeneic hepatocytes.


RESULTS
Similar results were observed after allotransplantation and xenotransplantation. Histologic studies showed that hepatocytes were well-preserved and arranged in cords for up to 30 days. The expression of porcine albumin gene was maintained up to 15 days. 6beta-Hydroxylase activity was 2.5-fold lower at day 15 than in freshly encapsulated hepatocytes, which were not transplanted. In allogeneic hepatocytes, the expression of CYP 3A protein was detected up to 60 days after transplantation.


CONCLUSIONS
Encapsulated porcine hepatocytes remain viable and functional for at least 15 days after allotransplantation and xenotransplantation without immunosuppression. The demonstration of maintained hepatic functions in transplanted porcine hepatocytes up to 15 days is a first step toward application in the treatment of acute liver failure.
Benoist
S
S
Research Unit 402 of INSERM, Paris, France.
Sarkis
R
R
Barbu
V
V
Honiger
J
J
Baudrimont
M
M
Lakehal
F
F
Becquemont
L
L
Delelo
R
R
Housset
C
C
Balladur
P
P
Capeau
J
J
Nordlinger
B
B
D000418:Albumins / Q000235:genetics; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002214:Capsules; D002470:Cell Survival / Q000276:immunology; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015870:Gene Expression; D006085:Graft Survival / Q000276:immunology*; D022781:Hepatocytes / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D006915:Hydroxytestosterones / Q000378:metabolism; D007165:Immunosuppression Therapy; D017114:Liver Failure, Acute / Q000276:immunology / Q000628:therapy; D019164:Liver, Artificial; D008854:Microscopy, Electron; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D000418:Albumins; D002214:Capsules; D006915:Hydroxytestosterones; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating