Mitochondrial dysfunction has been linked to many diseases including organ degeneration and cancer. Mesenchymal stem cells/stromal cells (MSCs) provide a valuable source for stem cell-based therapy and represent an emerging therapeutic approach for tissue regeneration. Increasing evidence suggests that MSCs can directly donate mitochondria to recover from cell injury and rescue mitochondrial damage-provoked tissue degeneration. Meanwhile, cancer cells and cancer stromal cells also cross-talk through mitochondrial exchange to regulate cancer metastasis. This review summarizes the research on MSCs and their mitochondrial transfer. It provides an overview of the biology, function, niches and signaling that play a role in tissue repair. It also highlights the pathologies of cancer growth and metastasis linked to mitochondrial exchange between cancer cells and surrounding stromal cells. It becomes evident that the function of MSC mitochondrial transfer is a double-edged sword. MSC mitochondrial transfer may be a pharmaceutical target for tissue repair and cancer therapy.

Emergence of SARS-CoV-2 variants of concern (VOC) with progressively increased transmissibility between humans is a threat to global public health. Omicron variant also evades immunity from natural infection or vaccines1. It is unclear whether its exceptional transmissibility is due to immune evasion or inherent virological properties.We compared the replication competence and cellular tropism of the wild type (WT) virus, D614G, Alpha, Beta, Delta and Omicron variants in ex vivo explant cultures of human bronchus and lung. Dependence on TMPRSS2 for infection was also evaluated. We show that Omicron replicated faster than all other SARS-CoV-2 in the bronchus but less efficiently in the lung parenchyma. All VOCs had similar cellular tropism as the WT. Delta was more dependent on serine protease than other VOCs tested.Our findings demonstrate that Omicron is inherently able to replicate faster than other variants known to date and this likely contributes to its inherently higher transmissibility, irrespective of its ability to evade antibody immunity. The lower replication competence of Omicron in human lung may be compatible with reduced severity but the determinants of severe disease are multifactorial. These findings provide important biological clues to the transmissibility and pathogenesis of SARS-CoV-2 VOCs.

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Background The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health globally. Patients with severe COVID-19 disease progress to acute respiratory distress syndrome, with respiratory and multiple organ failure. It is believed that dysregulated production of pro-inflammatory cytokines and endothelial dysfunction contribute to the pathogenesis of severe diseases. However, the mechanisms of SARS-CoV-2 pathogenesis and the role of endothelial cells are poorly understood. Methods Well-differentiated human airway epithelial cells were used to explore the cytokine and chemokine production after SARS-CoV-2 infection. We measured the susceptibility to infection, immune response, and expression of adhesion molecules, in human pulmonary microvascular endothelial cells (HPMVECs) exposed to conditioned medium from infected epithelial cells. The effect of imatinib on HPMVECs exposed to conditioned medium was evaluated. Results We demonstrated the production of IL-6, IP-10 and MCP-1 from the infected human airway cells after infection with SARS-CoV-2. Although human pulmonary microvascular endothelial cells (HPMVECs) did not support productive replication of SARS-CoV-2, treatment of HPMVECs with conditioned medium collected from infected airway cells induced an up-regulation of pro-inflammatory cytokines, chemokines and vascular adhesion molecules. Imatinib inhibited the up-regulation of these cytokines, chemokines and adhesion molecules in HPMVECs treated with conditioned medium. Conclusions This study evaluates the role of endothelial cells in the development of clinical disease caused by SARS-CoV-2, and the importance of endothelial cell-epithelial cell interaction in the pathogenesis of human COVID-19 diseases.