External-beam radiotherapy as preparative regimen for hepatocyte transplantation after partial hepatectomy.
OBJECTIVE
The transplantation of donor hepatocytes is considered a promising option to correct chronic liver failure through repopulation of the diseased organ. This study describes a novel selective external-beam irradiation technique as a preparative regimen for hepatocyte transplantation.


METHODS
Livers of dipeptidylpeptidase IV (DPPIV)-deficient rats were preconditioned with external-beam single-dose irradiation (25 Gy) delivered to two thirds of the liver. Four days later, a one-third partial hepatectomy (PH) was performed to resect the untreated liver section, and 15 million wild-type (DPPIV+) hepatocytes were transplanted via the spleen into the recipient livers. The degree of donor-cell integration and growth was studied 8 h, 3 days, and 5 and 12 weeks after transplantation.


RESULTS
Transplanted hepatocytes integrated rapidly into the irradiated liver and proliferated as clusters, finally repopulating the host liver to approximately 20% hepatocyte mass. After 12 weeks, donor cells and their numerous descendents were fully integrated and expressed functional markers to the same extent as host hepatocytes.


CONCLUSIONS
We demonstrate that external-beam liver irradiation is sufficient to achieve partial repopulation of the host liver after hepatocyte transplantation, under the additional stimulus of one-third PH. The method described has potentially good prospects for its application in a clinically viable form of treatment.
Christiansen
Hans
H
Department of Radiotherapy, University Hospital Goettingen, Goettingen, Germany. hchrist@gwdg.de
Koenig
Sarah
S
Krause
Petra
P
Hermann
Robert Michael
RM
Rave-Frank
Margret
M
Proehl
Thomas
T
Becker
Heinz
H
Hess
Clemens Friedrich
CF
Schmidberger
Heinz
H
D000818:Animals; D049109:Cell Proliferation; D002908:Chronic Disease; D018819:Dipeptidyl Peptidase 4; D005260:Female; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000201:enzymology / Q000502:physiology / Q000637:transplantation*; D008099:Liver / Q000528:radiation effects; D017093:Liver Failure / Q000532:radiotherapy* / Q000601:surgery*; D051381:Rats; D011916:Rats, Inbred F344; D019172:Transplantation Conditioning / Q000379:methods*
D018819:Dipeptidyl Peptidase 4