Fig. 7: MSCs improve the prognosis of COVID-19 patients by modulating the immune esponse, promoting tissue repair, and suppressing NET release. | Cell Research

Fig. 7: MSCs improve the prognosis of COVID-19 patients by modulating the immune esponse, promoting tissue repair, and suppressing NET release.

From: Mesenchymal stem cell treatment improves outcome of COVID-19 patients via multiple immunomodulatory mechanisms

Fig. 7

MSCs orchestrate immunomodulatory functions in two main ways to restore a harmonious homeostasis of the immune microenvironment and promoting immune system recovery in COVID-19 patients. On the one hand, the treatment of patients with MSCs (1) induced mobilization of COVID-19 patient-derived VNN2+ HSPC-like cells to the peripheral blood of patients via upregulation of CSF3R and PTPRE; (2) induced upregulation of chemotaxis-related genes (CCL5, CXCR2, CX3CR1, and L-selectin) in activated monocytes, NK cells, pDCs, and memory T cells; (3) supported the function of T cells (upregulation of CD28) through MAPK-ERK/JNK signaling; and (4) promoted the differentiation of CD4+ T cells into Th cells (upregulation of CD28, CD40L, IL12R, STAT4 and STAT6) to assist in B cell activation (upregulation of CD19 and CD81). On the other hand, MSCs also inhibit the overactivation of immune cells and their immune response in patients, characterized by promoted immunomodulatory functions of pDC, and increased TGF-β1 in various immune cells, upregulation of FOXP3 in Th cells. Concordantly, MSC treatment induced novel immune responses and facilitated IgM+IgD+ B cell activation to promote repair of damaged lung tissue. Finally, MSC treatment reduced the production of neutrophil extracellular traps (NETs) in COVID-19 patients by upregulating kindlin-3 expression in immune cells to reduce the risk of immunothrombosis. mT, memory T cells.

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