| Embryonic stem cells (ESCs) is derived from the inner cell mass of mammalian blastocysts. As a major type of pluripotent stem cells, it possesses the ability to proliferate indefinitely in vitro while sustaining the ability to differentiate into all cell lineages of the three germ layers. ESC is not only an ideal in vitro model for developmental biology research, but also a potential cell source for regenerative medicine. The molecule mechanism that promote the proliferation of ES cells is one of the core question in stem cell biology and have been subjected to intense study. The self-renewal and differentiation of ESCs are coordinatively regulated by extracellular signaling molecules and intracellular signaling pathways. As major mediators between extracellular signal and intracellular pathways, transmembrane proteins played critical roles in self-renewal of ES cells. Thus, screening for novel functional surface proteins in ES cells would significantly improve the understanding of proliferation mechanisms of ESCs.Kidins220/ARMS, a multiple transmembrane protein, had been shown to mediate signals from the neurothrophin signal pathways and contributed to cell survival and proliferation. As it has never been shown to express on ES cells, we set out to determine the function of Kidins220/ARMS in mES cells. From the data generated by surface proteomics analysis of ES cell surface proteins, we identified Kidins220/ARMS as one of the novel surface proteins on mES cells, which was ulteriorly confirmed by real-t ime qRT-PCR and ICC. RNA interference technology was adopted to knockdown the expression of Kidins220/ARMS in mouse ESCs, and the results showed that the proliferation was significantly inhibited by the down-regulation while the self-renewal was unaffected. It impl ied that Kidins220/ARMS was important to proliferation of ES cells but not to the sustenance of differentiation potential. The further dissection of the molecule mechanism that Kidins220/ARMS promote the proliferation of ESCs would significantly improve the understanding of stem cell proliferation and make implication to the formulation of new culture systems for ESC culture.Acute kidney injury (AKI) is a serious clinical complication that would cause high morbidity and mortality. Although many potential treatments including calcium channel blockers, dopamine, endothelin antagonist and Diuretic excretion of peptides have been tested in clinical trials, they of ten fail and cause many side-effects. Therefore, stem cells may have great potential in AKI therapy, and more and more researchers applied stem cells in the treatment of diseaseOur group have developed a differentiation protocol and obtained a type of novel stem cells, human embryonic stem cell-derived mesenchymal progenitor cells (hESC-MPs). It possesses self-renewal ability, and could be differentiated into adipocytes, osteoblasts and chondrocytes. This is the first time to apply hESC-MPs to AKI therapy. In this study, hESC-MPs were transplanted into Cisplatin-induced AKI mice, significant improvement of renal function and recovery of impaired renal structure were observed. Further studies showed that the transplanted hESC-MPs successfully homed to the injury area in kidney and promoted the proliferation and suvival of kidney cells. Moreover, the transplantation of hESC-MPs activated the expression of anti-inflammatory factors like IL-10; pro-survival factor like IGF-1, bFGF, FIGF, and inhibited the expression of chemokine MCP-1 and proinflammatory factors like IL-1β, TNF-α, IFN-γ, IL-6, TGF-β. These indicated that the immune-modulatory properties of hESC-MPs play an important role in the recovery of renal function. These results indicated that hESC-MPs may provide a promising new cell source for cell-based therapies for AKI and other complex, multifactorial disorders. |
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