Role of IGF1R+ MSCs in modulating neuroplasticity via CXCR4 cross-interaction

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, an insulin-like growth factor 1 receptor (IGF1R)–expressing sub-population in human dental...

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Veröffentlicht in:Scientific reports 2016-09, Vol.6 (1), p.32595-32595, Article 32595
Hauptverfasser: Lee, Hsu-Tung, Chang, Hao-Teng, Lee, Sophie, Lin, Chen-Huan, Fan, Jia-Rong, Lin, Shinn-Zong, Hsu, Chung Y., Hsieh, Chia-Hung, Shyu, Woei-Cherng
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container_title Scientific reports
container_volume 6
creator Lee, Hsu-Tung
Chang, Hao-Teng
Lee, Sophie
Lin, Chen-Huan
Fan, Jia-Rong
Lin, Shinn-Zong
Hsu, Chung Y.
Hsieh, Chia-Hung
Shyu, Woei-Cherng
description 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, an insulin-like growth factor 1 receptor (IGF1R)–expressing sub-population in human dental pulp MSCs (hDSCs), displayed multipotent properties. IGF1R expression could be maintained in hDSCs when they were cultured in 2% human cord blood serum (hUCS) in contrast to that in 10% fetal calf serum (FCS). Cytokine array 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, a bidirectional cross-talk between IGF1R/IGF1 and CXCR4/SDF-1α 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, enhancing angiogenesis and anti-inflammatiory effects. Therefore, PDGF in hUCS-culture system contributed to the maintenance of the expression of IGF1R in hDSCs. Furthermore, implantation of IGF1R + hDSCs exerted enhanced neuroplasticity via integrating inputs from both CXCR4 and IGF1R signaling pathways.
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subjects 13/100
631/337/2265
631/378/87
Angiogenesis
Cell culture
Cell self-renewal
Cord blood
CXCR4 protein
Cytokines
Dental pulp
Fetal calf serum
Growth factors
Humanities and Social Sciences
Insulin
Insulin-like growth factor I
Mesenchyme
multidisciplinary
Neuroplasticity
Platelet-derived growth factor
Platelet-derived growth factor BB
Pluripotency
Rodents
Science
Signal transduction
Stem cell transplantation
Stem cells
Stroke
Therapeutic applications
Transplantation
title Role of IGF1R+ MSCs in modulating neuroplasticity via CXCR4 cross-interaction
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