Page 8 - Mesenchymal Stem cells, Exosomes and vitamins in the fight aginst COVID

Expanded Umbilical Cord Mesenchymal Stem Cells as a Strategy In Managing COVID-19 Illness

there is no cure presently for this disease and vaccina- use of autologous cell therapy products (95). Despite
tion would not be available for several months. This and in full view of the above, stem cell therapy may
leaves a large unmet need for a safe and effective treat- have a role in managing COVID-19 disease (3,16,59,96-
ment for COVID-19 infected patients, especially the se- 101). The news of reports of stem cell therapy in China
vere cases (12,13,16,17). with publication of the details of a case of a critically
Multiple treatment strategies in the pipeline in- ill 65-year old Chinese woman infected with COVID-19,
clude antiviral therapy (1,16,36,37), hydroxychloroquine whose conditions improved after the infusion of MSCs
and combinations (34,35,37,39), neutralizing antibodies (96,97). They also reported that 7 other coronavirus
(18-21), repurposing currently available antiviral medi- patients in Beijing who had the stem cell therapy re-
cations (1,16,22-28,36,37), and passive antibody trans- sponded in a similar way (3).
fer from convalescent patients’ sera (29,30). Other new The newspaper also noted that this case is one
therapies include development of blocking agents that of many using stem cells to treat coronavirus patients
bind to ACE2 receptor (31-33,46-49). ACE2-positive cells in China, according to the WHO’s clinical trial database.
are infected by the HCoV-19, like SARS-2003 (50,51). The Zhang Xinmin, director of biological technology at the
ACE2 receptor is widely distributed on human cell sur- Ministry of Science and Technology in Beijing, told a
face, especially the alveolar type II cells (AT2) and capil- press conference on February 15 that the preliminary
lary endothelium (52), and the AT2 cells highly express results of stem cell experiments conducted across the
TMPRSS2 (53). country suggested the technology was “safe and effec-
While immunological therapy may be feasible, tive”. Such statements should be interpreted with cau-
the immunomodulatory capacity may be not strong tion (45).
enough, if only one or 2 immune factors were used, as
the virus can stimulate a cytokine storm in the lung. Cy- 2.0 PathogenesIs of coronavIrus
tokine storm can lead to acute respiratory distress syn- The S protein on Coronavirus surface specifically
drome (ARDS), acute cardiac injury, secondary infection, recognizes the spike protein in the angiotensin I con-
leading to generalized sepsis and multisystem failure, verting enzyme 2 receptor (ACE2) of the exposed cell
which may lead to death (3,17). Thus, avoiding the cy- and after binding, the virus enters the cell thereby in-
tokine storm may be the key for the treatment of CO- fecting it (1,3,47-53). Unfortunately, the ACE2 recep-
VID-19 infected patients. tor is widely distributed on the human cells surface,
Since there are a lack of effective therapies and especially the AT2 of the lungs (52,57). ACE2 receptors
immunological treatments may be insufficient, mesen- are also abundantly found in the heart, liver, diges-
chymal stem cells (MSCs), owing to their powerful im- tive organs and kidneys. In fact, almost all endothelial
munomodulatory ability, may have beneficial effects cells and smooth muscle cells in organs express ACE2,
for preventing or attenuating the cytokine storm and therefore once the virus enters the blood circulation,
reducing morbidity and mortality of this disease. it spreads widely. All tissues and organs expressing
Cell-based therapies are being incorporated into ACE2 could be the battlefield of the novel coronavi-
treatment plans for a number of disease processes in- rus and immune cells. This explains why beyond ARDS,
cluding pulmonary (54-60), cardiovascular (61-63), he- patients might also experience acute myocardial injury,
patic (64-66), renal (67-69), and other conditions (60,70- arrhythmia, acute kidney injury, shock, and death from
76). Generally, the use of cell-based therapy has greatly MOD syndrome (3,17). However, the cure of COVID-19
outpaced the evidence (60,70-76). Unfortunately, this is essentially dependent on the patient’s own immune
led to unsubstantiated claims of miraculous outcomes system. When the over activated immune system kills
(77). As a result, the Federal Trade Commission (FTC) the virus, it produces a large number of inflammatory
has taken action against stem cell therapy clinics found factors, resulting in severe cytokine storm (3,17). The
to be in violation of the truth in advertising law (78). main reason for organ damage may be due to virus-
Subsequently, the Food and Drug Administration (FDA) induced cytokine storm caused by IL-2, IL-6, IL-7, GSCF,
has investigated multiple stem cell clinics and published IP10, MCP1, MIP1A, and TNFα, followed by the edema,
new guidance (79-94). Further, the sheer volume of dysfunction of the air exchange, ARDS, acute cardiac
unsubstantiated claims and lack of high level research injury and the secondary infection, which may lead to
has led to a Health Canada policy position paper on the death (17).

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