Comprehensive immune cell analysis of human menstrual-blood-derived stem cells therapy to concanavalin A hepatitis

Abstract

Autoimmune hepatitis is an autoimmune disease with increasing occurrence worldwide. The most common and convenient mouse model is the concanavalin A (ConA) mouse model. Human menstrual-blood-derived stem cells (MenSCs) have shown great potential as a type of mesenchymal stem cell for treating various diseases. Time-of-flight mass cytometry was performed in phosphate-buffered saline control (NC) group and ConA injection with or without MenSCs treatment groups, and conventional flow cytometry was used for further validation. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and H&E staining depicted that MenSCs treatment could significantly alleviate ConA-induced hepatitis. The t-distributed stochastic neighbor embedding (t-SNE) analysis of nine liver samples displayed favorable cell clustering, and the NC group was significantly different from the other two groups. The proportions of CD69+ T cells, NKT cells, and PD-L1+ macrophages were notably increased by ConA injection, while MenSCs could decrease ConA-induced macrophage percentage and M1 polarization in the liver tissue. The analysis of proinflammatory factors carried out by cytometric bead array demonstrated that tumor necrosis factor alpha (TNF-α), interleukin (IL)-17A, IL-12p70, IL-6, IL-2, IL-1b, and interferon gamma (IFN-γ) were upregulated after ConA injection and then rapidly decreased at 12 h. MenSCs also played an important role in downregulating these cytokines. Here, we described the comprehensive changes in leukocytes in the liver tissue of ConA-induced hepatitis at 12 h after ConA injection and found that MenSCs rescued ConA-induced hepatitis mostly by inhibiting macrophages and M1 polarization in mouse liver.

Novel in vivo endometriotic models associated eutopic endometrium by implanting menstrual blood-derived stromal cells from patients with endometriosis

“…As for the potential application of these endometriotic models, we suggest that these models can be used for exploring the underlying role of eutopic endometrium in the pathogenesis, progress, and intervention of endometriosis. For instance, regarding the phenomenon of “progesterone resistance” in patients with endometriosis 37 , including 1/4–1/3 patients with endometriosis are no reaction to the first-line drug—combined oral contraceptives 38 , more and more studies indicate that eutopic endometrium in endometriosis is required to be further explored 21 , 39 , 40 . Some progesterone receptors (progesterone and adipoQ receptor 8 ( PAQR8 ) and progesterone and adipoQ receptor 6 ( PAQR6 )) are only reduced in eutopic endometrium and no significant difference between ectopic endometrium and the endometrium of women without endometriosis 41 .…”

CD73 mediates the therapeutic effects of endometrial regenerative cells in concanavalin A-induced hepatitis by regulating CD4+ T cells

“…Endometrial regenerative cells (ERCs), a kind of mesenchymal-like stromal cells derived from adult menstrual blood, exhibit the same immunomodulatory ability as mesenchymal stem/stromal cells (MSCs) and possess many advantages than MSCs [ 12 , 13 ]. We and others previously have demonstrated ERC’s valuable effectiveness in treating autoimmune and inflammatory diseases, including experimental hepatitis by the inhibition of CD4 + conventional T cells [ 14 – 16 ]. Currently, studies on the immunomodulatory mechanisms of ERCs are relatively rare in comparison with MSCs.…”