Page 91 - Mesenchymal Stem cells, Exosomes and vitamins in the fight aginst COVID

Pain Physician: August 2020 COVID-19 Special Issue 23:S391-S420

during CABG improved LVEF, ventricular remodel- Child Pugh scores, and ascites were noted in various
ing, and desynchrony (50-52). Two trials evaluating studies. In 2 studies, when bone marrow MSCs were
the effect of treating angina with MSCs revealed infused in the hepatic artery in patients with cirrho-
clinical and functional improvement (47,53). All tri- sis, histological improvement along with decreased
als that did not have a favorable outcome had bone fibrosis markers was seen (57,58). Another trial
marrow mononuclear cells except one study, which showed that by injecting bone marrow mononuclear
used expanded bone marrow stem cells. Among all cells into the hepatic artery, there was decreased inci-
these studies only 2 serious complications were not- dence of hepatic encephalopathy and bacterial peri-
ed. In one patient, during expanded bone marrow tonitis (59). Xue et al (56) found that when umbilical
MSC infusion, coronary occlusion was diagnosed cord MSCs were administered through the hepatic
by electrocardiogram changes and was successfully artery in patients with end-stage liver dysfunction,
treated with tirofiban and balloon inflation at the there was a decrease in hospitalization and increase
site of occlusion (54). In another study, one patient in the quality of life. Increases in liver volumes were
experienced chest discomfort and showed ST-T wave reported in 2 studies when bone marrow mononu-
changes, but spontaneous remission was achieved clear cells were used either IV or through the portal
15 minutes after physiological saline solution flush- vein (60,61). Importantly, 2 studies revealed increased
ing (55). Both patients had an uneventful recovery. survival rates. One utilized umbilical cord MSCs in the
hepatic artery and the other used bone marrow MSCs
Liver Failure intravenously (62,63). It is significant to note that
Liver disease, one of the major causes of human no serious complications were noted in any of these
mortality and morbidity worldwide, is a serious clini- studies. Although in one trial, when umbilical cord
cal syndrome. Generally, acute, or chronic liver dam- MSCs were administered through the hepatic artery,
ages could be caused by alcohol consumption, hepa- elevations were seen in bilirubin and ALT levels but
totoxic drugs, and virus infections, such as hepatitis interestingly, clinical improvement in terms of MELD
B virus and hepatitis C virus. Liver transplantation scores, ascites, and decreased hospitalizations were
offers an effective cure and is the criterion standard noted (56).
for treatment of end-stage liver disease. However,
several limitations regarding transplantation current- Stroke
ly restrict its application, such as limited number of Ischemic stroke is a leading cause of death and
donor organs, long waiting lists, high cost, potential a leading cause of disability in the Western world.
serious complications, and lifelong immunosuppres- IV thrombolysis remains the only proven therapy for
sion. Therefore it is an urgent task to explore new acute ischemic stroke. However, even in developed
treatment options for liver disease (56). countries, only a small minority of stroke patients cur-
We identified 23 clinical studies that assessed rently receive this therapy due to difficulty in access
the ability of MSCs to treat chronic/acute liver failure, and also timing. In addition, several neuroprotective
including end-stage liver disease, from different eti- strategies have failed to show any definite benefit af-
ologies ranging from alcoholic cirrhosis/primary bili- ter stroke. Acute ischemia causes irreversible damage
ary cirrhosis to hepatitis B. The studies are described to neurons and glial cells, leading to severe functional
in Table 3. Most studies were prospective controlled deficits and chronic sequelae. Cell therapy with bone
trials and case series along with 4 RCTs. In 10 studies, marrow–derived stem cells has shown to have ben-
hepatic artery infusion was performed, and in one eficial effects in animal models of stroke. Although
trial the MSCs were administered into the portal vein, the mechanisms involved are still subject to debate,
and the rest were IV. Eight studies utilized cultured it has been suggested that the injected cells release
bone marrow MSCs, mostly autologous; 6 used al- cytokines and trophic factors and modulate neuronal
logeneic umbilical cord MSCs; and in the remaining, death and inflammation in the penumbra area. There
nonexpanded bone marrow mononuclear cells were are no treatment options for the patients during
given. All trials except 3 reported positive outcomes. the poststroke period when they have difficulties in
Expanded bone marrow MSCs were used in 2 trials, performing activities of daily living, ambulation, and
and nonexpanded bone marrow MNCs were used in self-care. Use of stem cell–based therapy is becoming
the third. Improvements in LFTs, prothrombin time recognized as having the potential to improve the
(PT), model for end stage live disease (MELD) scores, neurologic function in poststroke patients.

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