Table 1.
Pre-clinical models of lung disease that received licensed MSCs.
| Murine Model | MSC Source | Route of Administration | Licensing Method | Licensing Location | Outcome | Ref |
|---|---|---|---|---|---|---|
| IPF (bleomycin) |
Mouse BM-MSC | I.T. | Hypoxia (1.5% O2) | in vitro | ↑ HIF1α, HGF, VEGF ↓ IL-6, pro-IL-1β |
[67] |
| ALI | Rat BM-MSC | In perfusate | Hypoxia (1% O2) | in vitro | ↑ IL-10, PGE2 ↓ Lung injury score ↓ TNF-α, IL-1β, MIP-2 |
[68] |
| ALI | Human UC-MSC | I.V. | TGF-β1 | in vitro | ↑ MSC survival ↑ Expression of RhoA ↓ LPS-induced injury |
[69] |
| ALI | Human UC-MSC (EVs) | I.V. | IFN-γ | in vitro | ↑ Animal survival ↑ eNOS ↓ Lung injury score ↓ TNF-α |
[70] |
| ALI | Rat lung MSCs | I.V. | Culture on lung ECM-cyclic stretch | in vitro | ↑ Lung elastance ↓ TNF-α, CXCL2 + neutrophils |
[71] |
| ALI | Human UC-MSC | I.N. | Heatshock (42 °C for 1 h) | in vitro | ↑ HSP70 expression ↑ IL-10 + PGE2 ↓ NLRP3 inflammasome formation ↓ IL-1β secretion by macrophages |
[72] |
| ALI | Human BM-MSC | I.V. | Co-culture w/ serum from ARDS patients | ex vivo | ↑ IL-10 + IL-1RN ↓ IL-6, IL-1α, IL-8, IL-1β, IFN-γ, TGFβ3, TGFβ2 + TNFAIP6 |
[73] |
| ALI | Human BM-MSC | AM treated with MSC- EVs-I.V. | Co-culture w/ BALF from ARDS patients | ex vivo | ↑ M2 macrophage marker expression ↑ Phagocytic capacity of human MDMs ↓ Cytokine production |
[74] |
| ALI | Human BM-MSC | I.T. | Cco-culture w/ plasma from ARDS patients | ex vivo | ↑ IL-6 production ↑ N-cadherin expression at mRNA + protein levels ↓ CD105 + CD90 marker expression at day 5 |
[47] |
| ALI | Mouse BM-MSC | I.V. | Co-culture w/ serum from ALI mice | ex vivo | ↑ Expression of anti-inflammatory mediators (TGF-β + IL-10) in AM in vitro ↓ iNOS + IL-6 |
[75] |
| Asthma | Mouse BM-MSC | I.T. | Co-culture w/ serum or BALF from asthmatic mice | ex vivo | ↑ TGF-β, IFN-γ, IL-10,TSG-6, IDO-1, IL-1RN, iNOS, TNF-α, IL-1β + arginase-2 ↑ caspase-3, bax ↓ bcl-2Serum:↓ IL-4, IL-13 + eotaxin |
[2] |
Footnote ↑ = Increased, ↓ = Decreased. Idiopathic Pulmonary Fibrosis (IPF), Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS), Bone-Marrow Mesenchymal Stromal Cells (BM-MSC), Umbilical-Cord Mesenchymal Stromal Cells (UC-MSC), Intratracheal (I.T.), Intranasal (I.N.), Intravenous (I.V.), Alveolar Macrophages (AM), Extracellular Vesicles (EV), Extracellular Matrix (ECM), Bronchoalveolar Lavage Fluid (BALF).