Hypothesis:
From an outbreak to an epidemic, World Health Organization (WHO)
declared the global spread of the COVID-19 as pandemic warranting
co-ordinated efforts for research and development into Diagnostics,
Novel Therapeutics and Repurposing of drugs for the control of
COVID-19(WHO, 2020). Respiratory failure caused by acute respiratory
distress syndrome (ARDS) is the leading cause of mortality. One of the
root causes for the ARDS is the cytokine storm which is acquired by
uncontrolled release of pro-inflammatory cytokine such as (IFN-α, IFN-γ,
IL-1β, IL-6, IL-12, IL-18, IL-33, TNF-α, TGFβ, etc.) and chemokines
(CCL2, CCL3, CCL5, CXCL8, CXCL9, CXCL10, etc.) by immune cells(Xiaowei
Li, Manman Geng, Yizhao Peng, Liesu Meng, 2020).
Interestingly, recent report suggest that intravenous transplantation of
MSCs decreased the over activated cytokine secreting immune cells such
as CXCR3+CD4+ T cells, CXCR3+CD8+ T cells with concomitant decrease in
C-reactive protein (CRP), Tumor Necrosis Factor-α (TNF- α) and increase
in the immunosuppressive cytokine IL-10(Leng et al. , 2020). To
everyone’s surprise, transplanted MSCs found to be resistant to the
COVID-19 infection and exhibited higher expression of anti- inflammatory
and trophic factors such as TGF-β, HGF, LIF, GAL, NOA1, FGF, VEGF, EGF,
BDNF(Leng et al. , 2020).
In search of a definitive viable solution to the dreadful COVID-19
infection, we propose stem cell Secretome as a promising therapeutic
option devoid of side effects. Secretome of MSCs which possesses potent
immunomodulatory effects which can counterbalance the pro-inflammatory
cytokines driven cytokine storm. As depicted in figure 1, conditioned
medium of MSCs which can be easily obtained by in-vitro cell culture and
can be locally administered through assisted nebulizer mask by
inhalation as initially proposed by us for the treatment of chronic
obstructive pulmonary disease (COPD)(Avinash Kharat, Vikrant Patil,
Supriya Kheur, 2019). Local administration of Secretome gives upper hand
over transplantation as it’s a cell free therapy employing rapid action
necessary as in the case of COVID-19 driven ARDS. Local and assisted
administration of MSCs Secretome will not only help counter balance the
cytokine storm driven by immunomodulatory properties but also promote
the cell survival, wound healing and anginogenic potential of resident
cells by its paracrine effect mediated by VEGF, EGF, HGF, FGF, CNTF, and
various interleukins(Ullah, Subbarao and Rho, 2015). We strongly
recommend MSCs Secretome nebulisation prior to the use of ventilator
which would avoid further complications. Combinatorial strategy of
antiviral drugs along with immunomodulatory, tissue protective and
healing potential of Secretome may reduce the severity of the COVID-19.
An urgent development is warranted on the MSCs Secretome based
therapeutics specifically targeted towards ARDS to ensure the health and
survival of human being.