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Allogenic Hepatocyte Transplantation Inimmunomodulated Lewis Rats with Acute Liver Insufficiency following Hepatectomy
Ist Teil von
Journal of the Egyptian Society of Parasitology, 2014-04, Vol.44 (1), p.221-228
Ort / Verlag
Cairo - Egypt: The Egyptian Society of Parasitology
Erscheinungsjahr
2014
Quelle
Alma/SFX Local Collection
Beschreibungen/Notizen
-Orthotropic Liver transplantation (OLT) is a conventional management for end-stage
acute or chronic liver insufficiency, but the shortage of donor organs continues to be the
restrictive factor throughout the world. Hepatocyte transplantation (HCTx) might be the
promising treatment for several liver diseases and can be used as a "bridge" to OLT.
Hepatocytes transplantation can protect and even save human lives, its’ applicability remains
limited by the large deficiency of liver organs and hepatocytes (HC), and cellular
loss after engraftment. Host elimination of grafted cells is called Early Graft Dysfunction.
This study was developed for an efficient protocol of HCT. Several conditions have
been met in order to achieve a high yield of harvested viable HC, overcome the detachedcell
apoptosis, attenuation of innate immune reaction against transplanted cells and a receptive
cell environment. HC were isolated from Lewis rats (n=8) weighing 250gm, by
the 2 step collagen a seper fusion technique, and bone marrow cells (BMCs) were obtained
from the rats tibia and femur by centrifugation in a buffer solution. The mean viability
of harvested HC and BMCs were 90% and 95% respectively.
To minimize the rejection of HC, Lewis rat recipients (n=14) weighing 250gm, were irradiated
with 6 Gy and received 0.1 mg of anti-aisle GM1 antiserum intravenously as immunosuppressive
drug. The isolated HC were intra-splenically transplanted and 107 bone
marrow cells were injected in a penile vein into the recipients on the third day. Simultaneously,
70% hepatectomy and ligation of common bile duct were done. Thirty days later;
the grafted spleen had areas with external appearance of a normal liver in ten out of
14surviving rats (71%). Hematoxlin and eosin (H & E) staining of sections from these
fragments showed sinusoids and portal areas, an evidence of successful hepatocyte engraftment
and bile canaliculea formation. Large number of HC clusters of 15 to 20 cells
and 2 to 4 distended small bile canaliculea were seen per50 HC. The intrasplenic route for
transplanting freshly isolated HC in an immune-compromised animal model was found to
give good results regarding cell engraftment and tissue formation.