الفهرس 
REVIEW OF LITERATUREOnly 14 pages are availabe for public view
Abstract
Liver cirrhosis is a significant lethal health problem all
over the world. Liver transplantation is the only efficient
treatment. Unfortunately, it is limited due to many obstacles.
Therefore, alternative treatments are required for cirrhosis.
Platelet rich plasma (PRP) and adipose tissue derived
mesenchymal stem cells (ADSCs) are a challenging measure
for treatment of cirrhosis.
This study aimed to assess the effect of PRP versus
ADSCs on Carbon tetrachloride (CCL4) experimentally
induced liver fibrosis in adult female albino rats.
Forty two adult albino female rats of average weight 200
gm were included in this study. In addition to twenty youngweaned rats (five males and fifteen female) of average weight
80-90 grams were used for preparation of PRP and ADSCs.
The adult female rats were divided into three main groups:
group I: Control group: 18 rats were subdivided into 3
subgroups 6 rats each:
Subgroup IA: 6 rats that received nothing and served as
negative control.
Subgroup IB: 6 rats that received 0.5 ml of olive oil
intraperitoneal (vehicle of CCL4).
Subgroup IC: 6 rats that received 1 ml of PBS in caudal
vein (vehicle of stem cells).
group II: CCL4 treated group: 12 rats for induction of
liver fibrosis and were subdivided into 2 subgroups 6 rats each:
Subgroup IIA: 6 rats that received CCL4 by
intraperitoneal injection in dose of 0.5 mg/kg twice weekly and
after six weeks they were sacrificed. For preparation, 20mg. of
CCL4 were dissolved in 100 ml. of olive oil. Each rat received
0.5 ml of the solution twice weekly.
Subgroup IIB: 6 that rats received CCL4 in the same
dose and route as subgroup IIA, but they were sacrificed after
another 4 weeks from the last CCL4 dose.
group III: PRP and ADSCs treated group: 12 rats were
subdivided into 2 subgroups 6 rats each:
Subgroup IIIA: 6 rats that received CCL4 for induction
of fibrosis as in group II for six weeks then received PRP
injection subcutaneously in a dose of 1ml/kg twice weekly for
four weeks and then were sacrificed.
Subgroup IIIB: 6 rats that received also CCL4 for
induction of fibrosis as in group II for six weeks but then
received ADSCs injection in caudal vein in a dose of 3x106
cells/rat in 1 ml PBS and were sacrificed after four weeks. Rats of all groups were sacrificed 4 weeks after the last
CCL4 dose except subgroup IIA. The liver specimens were
collected and processed for histological and
immunohistochemical staining for light microscopic
examination, and also for detection of Y chromosome.
Morphometric and statistical analysis were done.
The homing of the male donor cells was confirmed in the
injured liver of female recipients by PCR for the sry gene. The
Y chromosomes appeared in the liver of the female rats of
subgroup IIIB.
The light microscopic examination of H and E stained
sections of group II showed loss of hepatic architecture in many
fields with mononuclear cellular infiltration. Most of the
hepatocytes were vacuolated while others appeared with deep
acidophilic cytoplasm and deeply stained nuclei. Congestion of
the blood sinusoids as well as in the blood vessels at the portal
areas was noticed. Cirrhotic nodules of variable shapes and size
were found later in subgroup IIB.
There was an apparent reduction in the PAS positive
granules in the cytoplasm of the hepatocytes in comparison to
that of the control group.
In Masson’s trichrome stained sections, a significant
increase (P<0.05) in the area percentage of collagen was
detected around the central vein and the portal area as well as in the thickened capsule and the cirrhotic nodules as compared to
that of control animals. There was also a significant increase
(P<0.05) in the area percentage of α-SMA positive cells while
there was a non-significant difference (P>0.05) of the number
of PCNA positive cells in group II as compared to control
group. There was also significant increase in mean number of
caspase-3 positive cells and the area percentage of antivimentin as compared to the control group.
Light microscopic examination, in the current work
revealed that PRP and ADSCs treatment of rats of both
subgroups IIIA and IIIB showed marked improvement of the
liver structure.
Most of the hepatocytes showed acidophilic cytoplasm
with occasional basophilic granules but some still showing
slight cytoplasmic vacuolation. Mild mononuclear cellular
infiltration was observed. Congestion of blood sinusoids as
well as the blood vessels in the portal area in some fields was
also noticed. The cytoplasm of the hepatocytes showed
apparent normal content of PAS positive granules as that seen
in the control group. Significant decrease in area percentage of
collagen and the area percentage of α-SMA positive cells in
both subgroups IIIA and IIIB as compared to group II was
detected (p<0.05). Significant increase in the mean number of
PCNA positive cells as compared to both control and group II
was also found (p<0.05). In addition, significant decrease in the
mean number of caspase-3 positive cells and the area percentage of anti-vimentin as compared to group II was
recorded (p<0.05). There was an apparent more improvement
after treatment with PRP in subgroup IIIA than treatment
subgroup IIIB in H and E examination in the form of more
prominent basophilic granules. However, there was nonsignificant difference in all the statistical measures between
both modalities of treatment (p>0.05).