Page 30 - Mesenchymal Stem cells, Exosomes and vitamins in the fight aginst COVID

Al-Khawaga and Abdelalim Stem Cell Research & Therapy (2020) 11:437 Page 11 of 33

Table 2 Biological effect and molecular mechanisms of MSCs and MSC-EVs in preclinical and clinical studies looking into lung injury
(Continued)
Disease Study and/or cell Postulated Mechanism of MSC Route of MSC and/or MSC-MV EV isolation Reference
type action administration
(antimicrobial)
- Reduced the total bacterial load,
inflammation, and lung protein
permeability in the injured alveolus
in mice
- Decreased TNF-
- Restoration of intracellular ATP
levels in injured human AT2
(primary human AT2 culture)
- TLR3 prestimulation increased
mRNA expression for COX2 and IL-
10
Silicosis-induced - Human BM-MSCs - EVs outsource mitophagy, improve -40 μg protein (3 × 10 11 EVs), IV UCF [130]
lung injury/silica- - Mouse MSCs mitochondria bioenergetics via
exposed mice ARMMs
- Represses TLR signaling in
macrophages
- Repress the production of
inflammatory mediators via TLRs
and NF-kB pathway (miR-451)
- Prevent the recruitment of Ly6C hi
monocytes and reduces IL-10 and
TGF-β secretion (pro-fibrotic) by
these cells in the lung of silica-
exposed mice
Emphysema/ Human AD-MSCs - EV transfer to alveolar epithelium- -IT UCF (100, [131]
elastase-induced FGF2 signaling - 1 mg nanovesicle from 7 × 10 7 000×g force).
6
COPD model ASCs (30 × 10 nanovesicle Nanovesicle
generated) 100-nm
ALI (HPH) - Mouse BM-MSCs - EV transfer to endothelial cells -IV UCF (100 [132]
- Human UC-MSCs suppress STAT3 signaling - 0.1–10 μg MSC-derived kDa cut-off/
- Upregulation of the miR-17 super- exosomes Millipore)
family of microRNA clusters
- increased lung levels of miR-204
- Suppress pulmonary influx of
macrophages
PAH - Murine MSC(mMSC) - Prevent and reverse pulmonary -25 μg of MVs, IV UCF (100, [133]
- Human BM-MSCs remodeling via EV miRNA transfer 000×g)
- Increased levels of anti-
inflammatory, anti-proliferative miRs
including miRs-34a, -122, -124, and
-127.
BPD (hyperoxia) - Human UC-MSC - Reduced mRNA levels of pro- - 0.9–3 μg protein, IV UCF [134]
- Human BM-MSCs inflammatory M1 macrophage (OptiPrep/
markers (Tnfa, Il6, and Ccl5). EVs 30–150
- Enhanced M2 macrophage marker nm)
(Arg1)
- Suppressed the hyperoxic induction
of Cd206
- Significantly suppressed Retnla
BPD (hyperoxia) Human UC-MSCs - TSG-6-expressing EV transfer - 2.4–2.8 μg EVs (obtained from UCF [135]
6
- Decrease in IL-6, TNF-α, and IL-1β 0.5–1× 10 MSC), IP
5
Bleomycin (BLM)- - Mouse BM-MSCs - Block upregulation of IL-1 gene -5 × 10 MSCs, IV N.A. [136]
induced lung - Human BM-MSCs expression
inflammation and - IL1RN expressed by MSCs blocks
fibrosis release of TNF-α from activated
macrophages
- IL1RN is the principal IL-1 antagonist
secreted by murine MSCs
ALI (endotoxin Mouse-BM-MSCs - Decreased total WBCs, neutrophils, - IT MSCs administration -Transwell [137]
induced) MIP-2, EVLW, and TNFα - 20,000 cells/100 μl for co-culture
- Increase expression of KGF mRNA in in vitro and transwell