Page 99 - Mesenchymal Stem cells, Exosomes and vitamins in the fight aginst COVID

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

of 1 million/kg of cultured menstrual stem cells in commonly used MSCs in the United States (68,70). De-
conjunction with standard treatment. Forty-four spite spending billions of dollars, conventional treat-
similar patients receiving conventional therapy with- ment has been uninspiring in treating back pain. MSC
out stem cell therapy served as controls. Matching therapy seems to be filling this void and hopefully
was comparable except that patients in the treat- can mitigate the numerous problems associated with
ment group had a higher incidence of shock, circu- intractable pain, including opioid abuse (71). Early
latory failure, fatigue, and shortness of breath than clinical trials have demonstrated that MSCs can be a
the control cohort. Regardless, the survival rate was valuable alternative for joint replacements and spinal
significantly higher in the stem cell–treated groups fusions (68,70). Because preliminary evidence shows
versus control group (82.4% vs. 45.5%). Among pa- that MSCs have the potential to make strides in re-
tients who survived, stem cell group patients had calcitrant back and joint pain, especially in those who
significant improvement in procalcitonin, serum cre- have failed conventional therapies, it is worthwhile
atinine, 5-aminolevulinic acid, creatinine kinase, PT, to explore the role of MSCs in complicated COVID-19
and D-dimer levels when compared with the control patients, as meaningful alternatives do not currently
group indicating improvement in multiorgan failure. exist. Based on early evidence that MSCs are safe and
No complications were noted during the trial and effective in seriously ill COVID-19 patients, a call for
also among 4 of these patients who were followed FDA approval for compassionate use was published
for 5 years (39). as early as March 2020 (72). Fortunately, the FDA has
Early and preliminary data with small numbers been considerate and has approved various types of
seem to suggest that biologics can be promising stem cell treatments to treat COVID-19, and as per
and safe in patients with severe COVID-19 illness, media reports, the initial response is encouraging.
especially if they are not responsive to conventional Organ failure is the culmination of various insults
treatments. resulting in cellular death and dysfunction. Currently,
there are no pharmaceuticals that can reverse cellular
Discussion
injury and unfortunately organs are not capable of
There is no treatment for COVID-19 complicated meaningful self-regeneration. The only remaining
by ARDS, septic shock, and multiorgan failure, which option for severe liver, heart, or kidney failure is or-
is usually associated with a high mortality rate. gan transplantation, but has inherent shortcomings,
Conventional treatments, such as antivirals, immu- such as expense, accessibility (usually performed in
nomodulators, such as chloroquine, hydroxychloro- tertiary settings), availability of donor organs, surgi-
quine, and convalescent plasma, have not shown to cal complications, and lifelong immunosuppression.
be very effective. In a large trial, touted as one the For certain organs, such as the brain, it is not an op-
best antiviral drugs for COVID-19, Remdesivir had a tion. Based on the clinical evidence presented earlier,
mortality rate of 8.0% versus 11.6% for the placebo although stem cells cannot engraft (regardless of the
group and this result was not statistically significant route of administration) and differentiate into organ
(67). Therefore it is urgent to find a safe and effec- cells, they are, however, through their paracrine
tive therapeutic approach to treat COVID-19 com- activity, capable of organ regeneration, restoring
plications. Preliminary small studies with MSCs are function and increasing the survival rates. Most im-
showing promise in managing organ failures from portantly, as numerous studies have demonstrated, if
different etiology and also in seriously ill COVID-19 MSC therapy is conducted appropriately, the compli-
patients who are not responding to traditional cation rate seems to be negligible. Although MSCs
treatments. These studies have demonstrated that are immunoprivileged they are not immune evasive.
MSCs are capable of improving organ function by However, immune rejection, even after repeated dos-
regeneration. Bone marrow stem cells have a 30-year es of allogeneic MSCs, is a rare phenomenon (73). The
history of safety and efficacy in the musculoskeletal concern of tumorigenicity exists for embryonic and
arena (68). A meta-analysis of various studies using iPSCs, however, it seems to be extremely low for adult
biologics to treat back pain has been encouraging and fetal stem cells (74). Because these donor cells
(69). Because bone marrow MSCs seem to be FDA al- rarely engraft and disappear within a few weeks, the
lowed, as they meet the “minimal manipulation” and risk of altering the recipient’s karyotype or chimerism
“homologous use” criteria, they have been the most seems unlikely (75).

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