Stromal Cell-Derived Factor-1 Enhances the Therapeutic Effects of Human Endometrial Regenerative Cells in a Mouse Sepsis Model

Abstract

Endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells obtained from human menstrual blood, whose positive therapeutic effects have been validated in several experimental models. Stromal cell-derived factor-1 (SDF-1), the ligand for CXCR4, plays an important role in the migration of mesenchymal stromal cells. The purpose of this study was to investigate the role of the SDF-1/CXCR4 pathway in the therapeutic effects of ERCs in a mouse sepsis model. Through preexperiment and confirmation, wild-type C57BL/6 mice were intraperitoneally injected with 10 mg/kg lipopolysaccharide (LPS). The therapeutic effects of ERCs with different pretreatments were evaluated by assessing sepsis-related symptoms, detecting tissue damage and measuring levels of inflammatory and oxidative stress-related factors. The in vitro experiments demonstrated that there was a much higher CXCR4 expression on ERCs when they were cocultured with SDF-1. The ex vivo experiment results showed that SDF-1 expression significantly increased in mouse tissues. Further experiments also confirmed that, compared with the unmodified ERC treatment group, SDF-1 pretreatment significantly enhanced the therapeutic effects of ERCs on alleviating sepsis symptoms, ameliorating pathological changes, reducing Bax level, and increasing Bcl-2 and PCNA expressions in mouse liver tissues. Furthermore, it was also found that SDF-1-pretreated ERCs contributed to reducing the levels of proinflammatory cytokines (TNF-α, IL-1β) and increasing the levels of anti-inflammatory factors (IL-4, IL10) in mouse serum, liver, and lung. Moreover, SDF-1-pretreated ERCs could also significantly decrease the levels of iNOS and MDA and increase the expression of Nrf2, HO-1, and SOD in liver tissues. Taken together, these results indicate that SDF-1 pretreatment plays a key role in improving the therapeutic effects of ERCs in alleviating sepsis-related symptoms, reducing tissue damage, regulating inflammatory imbalance, and relieving oxidative stress in a mouse sepsis model, which provides more possibilities for the clinical application of ERCs in sepsis and relevant diseases.

Macrophage polarization by MSC-derived CXCL12 determines tumor growth

“…A series of G protein-coupled chemokine receptors, which are characterized by seven transmembrane domains, can be activated by the N-terminus part of CXCL12. CXCR4, a 352-amino acid molecule, is the main receptor for CXCL12, which transduces multiple signals after induction, resulting in a number of context-dependent biological functions such as proliferation, cell chemotaxis, migration, apoptosis, survival and differentiation [ 17 , 22 – 24 ].…”

Development of a stem cell spheroid‐laden patch with high retention at skin wound site

“…After removing the CLP on Day 3, most of the fluorescence signal remained at the wound site. In the wound site, enhanced expression of SDF‐1 alpha, a key factor for cell migration, induces the migration of injected cells to the wound site 27 . Since control group showed low cell viability and growth factor secretion, CLP group had more enhancement in wound healing effect compared with the control group (Figure S1).…”

Downregulation of Dickkopf-1 Augments the Therapeutic Effects of Endometrial Regenerative Cells on Experimental Colitis

“…On the contrary, IFN-γ, TNF-α, MPO, COX-2 and iNOs are pro-in ammatory factors which often strongly exacerbate the in ammations cascade in colitis [61][62][63]. ERCs, used for the immune-related diseases, were reported to have an ability to ameliorate the production and accumulation of in ammatory mediators, and thus to relieve the local tissue injury [19,64]. But, whether down-regulating DKK1 expression in ERCs, could also modulate the imbalance of in ammatory mediator pro les, and exit a more provoking effect has not been illustrated till now.…”