title: Role of IGF1R(+) MSCs in modulating neuroplasticity via CXCR4 cross-interaction.
abstract: 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.
authors: Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, 40421, Taiwan.|Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, 114, Taiwan.
authors: Hsu-Tung
authors: HT
authors: Lee
authors: Graduate Institute of Basic Medical Science, China Medical University, Taichung, 40421, Taiwan.
authors: Hao-Teng
authors: HT
authors: Chang
authors: Center for Neuropsychiatry, China Medical University Hospital, Taichung, 40440, Taiwan.|Graduate Institute of Life Science, Graduate Institute of Medical Sciences and Department of Neurology, National Defense Medical Center, Taipei, 114, Taiwan.
authors: Sophie
authors: S
authors: Lee
authors: Center for Neuropsychiatry, China Medical University Hospital, Taichung, 40440, Taiwan.
authors: Chen-Huan
authors: CH
authors: Lin
authors: Center for Neuropsychiatry, China Medical University Hospital, Taichung, 40440, Taiwan.
authors: Jia-Rong
authors: JR
authors: Fan
authors: Center for Neuropsychiatry, China Medical University Hospital, Taichung, 40440, Taiwan.|Graduate Institute of Immunology, China Medical University, Taichung, 40440, Taiwan.
authors: Shinn-Zong
authors: SZ
authors: Lin
authors: Graduate Institute of Clinical Medical Science, China Medical University, Taichung, 40421, Taiwan.
authors: Chung Y
authors: CY
authors: Hsu
authors: Graduate Institute of Basic Medical Science, China Medical University, Taichung, 40421, Taiwan.
authors: Chia-Hung
authors: CH
authors: Hsieh
authors: Center for Neuropsychiatry, China Medical University Hospital, Taichung, 40440, Taiwan.|Graduate Institute of Life Science, Graduate Institute of Medical Sciences and Department of Neurology, National Defense Medical Center, Taipei, 114, Taiwan.|Graduate Institute of Immunology, China Medical University, Taichung, 40440, Taiwan.
authors: Woei-Cherng
authors: WC
authors: Shyu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D000077214:Becaplermin; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D055495:Neurogenesis / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects; D033581:Stem Cell Transplantation; D020521:Stroke / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D000893:Anti-Inflammatory Agents; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D016207:Cytokines; D020574:Proto-Oncogene Proteins c-sis; D019718:Receptors, CXCR4; D000077214:Becaplermin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D005947:Glucose