Biomedical Engineering Reference
In-Depth Information
administration and subsequently isolated from the mononuclear cell fraction by
magnetic cell sorting. These cells were manipulated by plastic adherence and
cultured in media containing a number of cytokine (including stem cell factor,
GM-SCF, IL-3, and G-CSF. 1 9 10
6
-29 10
8
cells were reinfused via the
hepatic artery (n = 2) or portal vein (n = 3). There was no clear change in liver
biochemistry or clinical parameters over the initial 2 month period or on longer
term follow up of 12-18 months [
22
]. The same group also published a report of
nine patients with alcoholic cirrhosis who had been abstinent for a minimum of
6 months [
23
]. CD34+ cells were isolated following G-CSF administration and
cultured in similar conditions. A mean dose of 2.3 9 10
8
cells was injected into
the hepatic artery. There were no detected complications whilst liver biochemistry
and Child-Pugh score seemed to improve over a 3 month period.
The intraportal delivery of CD133+ BM cells has been examined in the context
of hepatic resection in non-cirrhotic patients by Furst et al. [
24
]. Thirteen patients
underwent portal vein embolization to stimulate regeneration prior to extended
right hepatectomy for large hepatic malignancy (primary and secondary). Six of
these patients additionally received 2.4 - 12.3 9 10
6
CD133+ cells that had been
positively selected from BM aspirate. This resulted in significantly greater gains of
hepatic volume allowing earlier tumour resection. One of the treated patients had
liver fibrosis due to HCV infection. In addition to non-cirrhotic liver surgery, it is
possible that these pro-regenerative effects could also occur in the pathophysio-
logically different context of the cirrhosis.
In a study from the Royan Institute, Iran, four patients with decompensated
cirrhosis were given 2.5 - 8 9 10
6
BM derived CD34+ cells via the hepatic artery
in a radiologically guided procedure [
25
]. One of these patients (autoimmune
aetiology) developed progressive renal failure and died of liver failure prompting
premature termination of the trial. The adverse event was linked to radiocontrast
nephropathy in a patient with advanced liver disease and pre-existing renal
impairment. This highlights the critical nature of issues such as patient selection
and route of cell administration.
Salama et al. [
26
] studied the effects of partially differentiated CD34+ cells in
48 cirrhotic patients (36 HCV, 12 autoimmune aetiology). Participants underwent
G-CSF mobilisation and leukapheresis. CD34+ cells were isolated, cultured and
amplified for a further 7 days in media containing GM-CSF and growth factors
derived from buffalo rat liver extract. The culturing process was intended to begin
hepatocytic differentiation. RT-PCR demonstrated that these cells were beginning
to express the genes for albumin and subsequently a1-antitrypsin during this
protocol. 1 9 10
9
cells were infused via the portal vein (or hepatic artery if
hepatofugal flow detected). Three serious complications were noted: haemoperi-
toneum post-procedure (stabilised with blood transfusion) and two GI bleeds
1 week after infusion (1 controlled endoscopically, 1 fatal). LFTs improved in
both the HCV and autoimmune aetiology patients in conjunction with clinical
assessment of ascites.
The same authors also conducted a randomised controlled trial of CD34/133+
cells in HCV cirrhosis [
27
]. Ninety patients received 5 days of G-CSF treatment
