Perspectives on mesenchymal stem/progenitor cells and their derivates as potential therapies for lung damage caused by COVID-19

Figure 1 Immune response to severe acute respiratory syndrome coronavirus-2 infection and immunoregulatory activity of mesenchymal stem cells for treatment in patients with coronavirus disease 2019 pneumonia. Upon entry into the alveolar epithelium, SARS-CoV-2 triggers a strong immune response with cytokine storm. Cytokines and trophic factors released by MSCs (ACE2 negative) and their derivate EVs modulate the inflammatory microenvironment within the damaged pulmonary cells and modulate immune response, promoting a shift from T helper type 1 to Th2 lymphocytes, and a shift in macrophage balance from the M1 (proinflammatory) to M2 (anti-inflammatory) phenotype, and decreasing the activity of cytotoxic T lymphocytes (Tc) and natural killer lymphocytes. ACE2: Angiotensin-converting enzyme 2; MSCs: Mesenchymal stem cells; Ang-1: Angiopoietin-1; SARS-CoV-2: Severe acute respiratory syndrome coronavirus-2; COVID-19: Coronavirus disease 2019; bFGF: Basic fibroblast growth factor; EGF: Epithelial growth factor; EVs: Extracellular vesicles; G-CSF: Granulocyte-colony stimulating factor; GM-CSF: Granulocyte-macrophage colony-stimulating factor; HGF: Hepatocyte growth factor; IFN-γ: Interferon-γ; IGF-1: Insulin-like growth factor-1; IL-: Interleukin-; KGF: Keratinocyte growth factor; MIP-1α: Macrophage inflammatory protein-1α; MIP-1β: Macrophage inflammatory protein-1β; SDF-1: Stromal-derived factor-1; TGF-α: Transforming growth factor-α; TGF-β: Transforming growth factor-β; TNF-α: Tumor necrosis factor-α; VEGF: Vascular endothelial growth factor; MCP-1: Monocyte chemoattractant protein-1; PGE2: Prostaglandin 2.