Human placenta-derived amniotic epithelial cells as a new therapeutic hope for COVID-19-associated acute respiratory distress syndrome (ARDS) and systemic inflammation

Table 1 Proposed therapeutic effects of hAECs and responsible mediators in COVID-19

Mediators	Mechanism	Effects	References
MIF	Immunomodulation	Prevention of cytokine storm	[27, 89]
IL-10
PGE2
HLA-G	Immunomodulation	Regulation of immune cells differentiation	[92]
IL-5	Immunomodulation	Modulation of hyper-inflammatory responses	[95]
		Improvement of humoral immune system
AMPs	Immunomodulation	Triggering early immune response	[101, 102]
		Prevention of nosocomial secondary bacterial infections
Ang-(1-7)	Regulating RAAS	Reduction of inflammation, fibrosis, thrombosis, and vasoconstriction	[20, 63, 104]
SP-A	Alveolar fluid clearance	Reduction of air–liquid surface tension	[22]
SP-B
SP-C
SP-D
TIMP-1	Alveolar fluid clearance	Prevention of inflammatory effects of MMPs	[116]
TIMP-2
IL-10	Eliminating hypercoagulopathies	Suppression of coagulation cascades by inhibiting monocytes-induced activation of TF	[26]
Perlecan	Eliminating hypercoagulopathies	Inhibition of thrombosis by inducing endothelial cell proliferation	[26]
Hyaluronic acid
PEDF	Eliminating hypercoagulopathies	Inhibition of platelet activation and aggregation through antioxidant capacity	[26]
MMP-9	Eliminating hypercoagulopathies	Prevention of platelet activation by suppressing the Na+/K+ exchanger and adjusting intracellular calcium balance	[26]
IL-4	Eliminating hypercoagulopathies	Inhibition of plasminogen activator, thrombomodulin, and protein C	[26, 127,128,129,130]
IL-10
IL-13

MIF, migration inhibitory factor; IL, interleukin; PGE2, prostaglandin E2; HLA, human leukocyte antigen; AMP, antimicrobial peptide; Ang, angiotensin; SP, surfactant; TIMP, tissue inhibitor of metalloproteinase; PEDF, pigment epithelium-derived factor; MMP, matrix metalloproteinase; RAAS, renin–angiotensin system

ISSN: 1757-6512