CXCR2 and Its Related Ligands Play a Novel Role in Supporting the Pluripotency and Proliferation of Human Pluripotent Stem Cells

Abstract

Basic fibroblast growth factor (bFGF) is a crucial factor sustaining human pluripotent stem cells (hPSCs). We designed this study to search the substitutive factors other than bFGF for the maintenance of hPSCs by using human placentaderived conditioned medium without exogenous bFGF (hPCCM -), containing chemokine (C-X-C motif) receptor 2 (CXCR2) ligands, including interleukin (IL)-8 and growth-related oncogene a (GROa), which were developed on the basis of our previous studies. First, we confirmed that IL-8 and/or GROa play independent roles to preserve the phenotype of hPSCs. Then, we tried CXCR2 blockage of hPSCs in hPCCM -and verified the significant decrease of pluripotency-associated genes expression and the proliferation of hPSCs. Interestingly, CXCR2 suppression of hPSCs in mTeSRÔ1 containing exogenous bFGF decreased the proliferation of hPSCs while maintaining pluripotency characteristics. Lastly, we found that hPSCs proliferated robustly for more than 35 passages in hPCCM -on a gelatin substratum. Higher CXCR2 expression of hPSCs cultured in hPCCM -than those in mTeSRÔ1 was observable. Our findings suggest that CXCR2 and its related ligands might be novel factors comparable to bFGF supporting the characteristics of hPSCs and hPCCM -might be useful for the maintenance of hPSCs as well as for the accurate evaluation of CXCR2 role in hPSCs without the confounding influence of exogenous bFGF.

Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells

“…4 D). Importantly, in line with the prostemness functions of ELR + chemokines (Liu et al, 2011; Jung et al, 2015), treatment with the CXCR-2 inhibitor also reduced the level of CD44 + CD24 low/− TICs within the breast carcinoma cells co-cultured with MTD-CAFs (Fig. 4 E).…”

“…Tumors with elevated levels of ELR + chemokines are more aggressive, and this phenotype has been attributed to their ability to stimulate angiogenesis or promote macrophage-induced immune suppression within tumors (Ali and Lazennec, 2007; Seifert et al, 2016). In addition, ELR + chemokines can also foster the growth and survival of stem cells (Liu et al, 2011; Jung et al, 2015). Consistently, both an in vitro angiogenesis assay and a tumor neovascularization assay revealed that the MTD-CAFs markedly promoted endothelial tube formation and tumor neovascularization, which could be efficiently blocked by SB225002, a specific inhibitor of the conserved ELR + chemokine receptor CXCR-2 (Fig.…”

CXCL6 is an important paracrine factor in the pro-angiogenic human cardiac progenitor-like cell secretome

“…Plasma GROa levels correlate inversely with severity of disease in an experimental murine model of myocarditis 43 . Both GROa and CXCR2 were recently implicated in human pluripotent stem cell pluripotency and proliferation 39 – 44 .…”

Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases

“…Inhibition of CXCR2 hindered hPSC self-renewal and resulted in a gradual increase in cell differentiation 350. The CXCL8-CXCR1/2 signaling regulates maintenance and cellular growth of glioblastoma stem cells.…”