The merits of autologous mesenchymal stem cells peripheral vein infusion in patients suffering from end stage liver cirrhosis_ Ayman Salah _ Cairo University_Egypt

Cirrhosis, the top result of prolonged liver damage, places a
major burden on healthcare worldwide. There are many
possible manifestations of cirrhosis. These signs and symptoms
may be a direct result of liver cells failure, or secondary to the
resultant increased pressure in the blood vessels in the liver
portal system. Cirrhosis of the liver is slow and gradual in its
development. It is usually well advanced before its symptoms
are noticeable because it is a cause of alarm. Weakness and
weight loss may be the initial symptoms. Cirrhosis usually
precedes hepatitis and liver disease (steatosis), which is
independent of the cause. If the cause is removed at this stage,
the changes are completely reversible. Liver transplantation is
the only definitive therapeutic option for these patients.
However, a worldwide reduction of donor liver has prompted
for alternative cell therapies. The potential clinical use of
autologous multipotent mesenchymal stem cells (MSCs)
isolated from bone marrow (BM) holds great promise for the
treatment of a large number of diseases that are in the late stage
liver disease. Sixty patients with hepatitis C virus (HCV) endstage
liver disease were included in this study. They were
randomly classified into two groups: Group 1: 35 patients
whose granulocyte colony-stimulating factor (G-CSF) was
administered for 5 days to mobilize their hematopoietic stem
cells. After leukapheresis, CD34 (+) stem cells were isolated,
amplified, and partially differentiated into culture, then reinjected
via peripheral-vein infusion. Group 2: 25 patients who
received only liver-supportive treatment (control group).
Hepatic fibrosis was assessed by detecting procollagen IIIC
peptide levels (PIIICP) and procollagen III N peptide levels
(PIIINP) in group I. In group I, liver functions were markedly
improved in 57.1% of patients. Albumin (P = 0.000), significant
changes in bilirubin (P = 0.002), international normalized ratio
(INR) (P = 0.017), prothrombin concentration (P = 0.029 with
stabilization of clinical and biochemical status in 14.3% of
cases). ) And alanine transaminase (ALT) levels (P = 0.029).
While no significant improvement was found in any of the
patients in group II. Pretreatment values of s-PIIICP and s-
PIIINP were 8.2 and 3.7 and 395 with 175, respectively, with a
decrease of 7.3 ± 2.1 and 338, 95 at 3 months after MSC
therapy, respectively, however, the difference was statistically
nonsignificant (p = 0.7). A significant coefficient of correlation
was reported between s-PIIINP and prothrombin concentration
(P = -0.5) and between s-PIIICP and ascites (P = 0.550 It is
often concluded that mixing G-CSF with MSCs will greatly
improve the outcome of stem cell treated patients with end
stage disease. In addition peripheral intravenous infusion is a
simple and convenient method of delivery of stem cells,
compared to the intrauterine infusion route with less-invasive
and less painful effects. Furthermore, IV infusion of MSCs after
G-CSF mobilization improves S-albumin within the first 2
weeks and prothrombin concentration and alanine transaminase
after 1 month. In addition, MSCs may act directly through
inhibiting collagen formation, as evident by their ability to scale
back liver fibrosis markers. Taken together, our data provide
evidence that CD34 (+) MSCs followed G CSF mobilization,
which is excellent for liver stem cell therapy to maintain liver
mass and restore liver function.

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Author(s): Ayman Salah

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