| Summary: | 博士 === 國防醫學院 === 醫學科學研究所 === 104 === In order to guide the use of human mesenchymal stem cells (MSCs) toward clinical applications, identifying pluripotent-like markers for selecting MSCs that retain potent self-renewal ability should be addressed. Here, we report an insulin-like growth factor 1 receptor (IGF1R)–expressing sub-population in human dental pulp mesenchymal stem cells (hDSCs), displayed self-renewal and multipotent properties. We found that IGF1R expression could be maintained in hDSCs when they were cultured in 2% human cord blood serum (hUCS) in contrast to hDSC cultured in 10% fetal calf serum (FCS). Cytokine array study showed that hUCS contained higher amount of several growth factors compared to FCS, including IGF-1 and platelet-derived growth factor (PDGF-BB). These cytokines modulates the signaling events in the hDSCs and potentially enhances engraftment upon transplantation. Specifically, we have characterized a bidirectional cross-talk between IGF1R/IGF1 and CXCR4/SDF-1 signaling pathways in hDSCs,as revealed by interaction of the two receptors and synergistic activation of both signaling pathways. In rat stroke model, animals receiving IGF1R+ hDSCs transplantation, interaction between IGF1R and CXCR4 was demonstrated to promote neuroplasticity, therefore improving neurological function through increasing glucose metabolic activity and enhancing angiogenesis. In addition, IGF1R+ hDSCs implantation significantly augmented neurite regeneration in stroked rats. In conclusion, PDGF in hUCS-culture system contributed to the maintenance of the expression of multipotent marker of IGF1R in hDSCs. Furthermore, implantation of IGF1R+ hDSCs exerted enhanced neuroplasticity in cerebral ischemic model via integrating inputs from both CXCR4 and IGF1R signaling pathways.
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