Table 1.
Preclinical and Clinical Studies Investigating the Effect of MSCs/MSC-Derived EVs in Respiratory Virus Infection.
| Study | Model/patient | Treatment | Mechanism | Reference |
|---|---|---|---|---|
| Chan et al (2016) | H5N1 influenza A virus-infected mice H5N1 influenza A viruses induced AECs |
Human BM-MSCs |
In vitro
↑ AFC and ↓ APP ↓ IL-1β, RANTES, IL6, IL8, and IP10 mRNA levels ↑ transporter proteins of CFTR, α1Na, and K-ATPase ↑ Ang-1 and KGF In vivo ↑ Survival and body weight in aged mice ↓Wet-to-dry lung weight, Evans blue dye in the lungs, and the concentration of total protein, most cytokine, and chemokine of the BALF in all mice. ↓ Peribronchial, perivascular, and overall histopathology scores. |
29 |
| Loy et al (2019) | Mouse ALI Influenza A/H5N1 virus induced AECs |
Human BM-MSCs and Human UC-MSCs |
In vitro
Restoration of AFC and APP (BM-MSCs, UC-MSCs, and UC-MSC secretome and exosomes) ↑ ENaC, Na+, K+-ATPase, and CFTR (both BM-MSCs and UC-MSCs) ↓ IFN-λ1, IL-6, IL-1β, IP-10, MCP-1, and RANTES (both BM-MSCs and UC-MSCs) and IFN-β (only UC-MSCs) ↑ IL-4, IL-10, IL-11, IL-13, and IL-1RA (both UC-MSCs and BM-MSCs) In vivo ↑ Body weight (UC-MSCs) ↓ Evans blue dye (UC-MSCs) ↓ IP-10, MCP-1, RANTES, TNF-α, IL1-β, IL-6 and IL-8 protein levels (UC-MSCs) |
30 |
| Li et al (2016) | Mice H9N2 avian influenza virus-induced ALI |
BM-MSCs of mice | ↑ Survival rate ↓ Lung weights and lung wet: dry weight ratios ↓ Airspace inflammation ↑ Lung histopathology ↑ PaO2, SaO2, and pH values ↓ PaCO2 ↓ GM-CSF, MCP-1, KC, MIP-1α, and MIG in both BALF and serum ↓ IL-1α, IL-6, IL-10, TNF-α, and IFN-γ in both BALF and serum ↓ CD14, TLR4, ERK and JNK protein in the lung tissue |
31 |
| Chen et al (2020) | Patients with H7N9-induced ARDS | Human menstrual-blood-derived MSCs | ↑ Survival rate ↓ PCT, ALT, sCr, CK, PT, D-Dimer In 4 patients with MSC transplantation during follow-up ↑ Hemoglobin levels ↓ PT Improvement in both lung function and lesions on CCT |
34 |
| Leng et al (2020) | Patients with COVID-19 | MSCs | ↓ Plasma CRP in one critically severe patient ↑ Oxygen saturation ↑ Lymphocyte ↓ ALT, CK activity and myoglobin Improvement on CCT ↑ Regulatory T cells and dendritic cell in the severe and critically severe patients ↑ CD14+CD11c+CD11bmid-regulatory dendritic cell and disappearance of overactivated T cells and NK cells in the critically severe patients. ↓ TNF-α ↑ IL-10 |
35 |
| Shu et al (2020) | Patients with severe COVID-19 | Human UC-MSCs | In the hUC-MSC group (compared with the control group) Reduced incidence of progression from severe to critical illness and reduced 28-day mortality rate Shorter time of clinical improvement Significantly lower levels of CRP and IL-6 from day 3 of infusion Significantly faster time of lymphocyte count to return to the normal range Significantly shorter time of lung inflammation absorption on CT imaging |
36 |
| Khatri et al (2018) | Pigs Influenza virus-induced ALI Influenza virus induced lung epithelial cells |
EVs from swine BM-MSCs |
In vitro
↓ Influenza replication ↑ Inhibition of apoptosis In vivo ↓ Infiltration of inflammatory cells and lung lesion score ↓ Total protein ↓ Virus shedding and virus titers ↓ TNF-α and CXCL10 ↑ IL-10 |
40 |
| Sengupta et al (2020) | Patients with severe COVID-19 | Exosomes (ExoFlo™) derived from allogeneic BM-MSCs | 83% of survival rate ↑ PaO2/FiO2 ↓ Absolute neutrophil count ↑ Average CD3+, CD4+, and CD8+ lymphocyte counts ↓ Mean CRP, ferritin, and D-dimer |
42 |
ALI: acute lung injury; AECs: alveolar epithelial cells; ARDS: acute respiratory distress syndrome; ALT: alanine aminotransferase; AFC: alveolar fluid clearance; APP: alveolar protein permeability; Ang-1: angiopoietin-1; BM: bone marrow; BALF: bronchoalveolar lavage fluid; COVID-19: coronavirus disease 2019; CRP: C-reactive protein; CK: creatine kinase; CCT: computed tomography of the chest; EVs: extracellular vesicles; FiO2: fraction of inspired oxygen; KGF: keratinocyte growth factor; MSCs: mesenchymal stem cells; PCT: procalcitonin; PT: prothrombin time; PaO2: partial pressure of oxygen; PaCO2: partial pressure of carbon dioxide in artery; sCr: serum creatinine; SaO2: arterial oxygen saturation; UC: umbilical cord.