title: IGF1R+Dental Pulp Stem Cells Enhanced Neuroplasticity in Hypoxia-Ischemia Model.
abstract: Until now, the surface markers of multipotent mesenchymal stem cells (MSCs) had not been fully identified. Here, we found that the IGF1 receptor (IGF1R), regarded as a pluripotent marker of embryonic stem cells (ESCs), was also expressed in human dental pulp derived-mesenchymal stem cells (hDSCs), which displayed a potential for both self-renewal and multipotency. hDSC-secreted IGF1 interacted with IGF1R through an autocrine signaling pathway to maintain this self-renewal and proliferation potential. Stereotaxic implantation of immunosorted IGF1R+hDSCs in rats with neonatal hypoxia-ischemia (NHI) promoted neuroplasticity, improving the neurological outcome by increasing expression of the anti-apoptotic protein Bcl-2, which enhanced both neurogenesis and angiogenesis. In addition, treatment with IGF1R+hDSCs significantly modulated neurite regeneration and anti-inflammation in vivo in NHI rats and in vitro in primary cortical cultures under oxygen/glucose deprivation. Autocrine regulatory expression of IGF1R contributed to maintaining the self-renewal capacity of hDSCs. Furthermore, implantation of IGF1R+hDSCs increased neuroplasticity with neurite regeneration and immunomodulation in and the NHI rat model.
authors.affiliation: Children's Hospital, China Medical University and Hospital, Taichung, Taiwan.|Translational Medicine Doctoral Degree Program, China Medical University, Taichung, Taiwan.
authors.forename: Hsiao-Yu
authors.initials: HY
authors.lastname: Chiu
authors.affiliation: Translational Research Center, and Department of Neurology, China Medical University Hospital, Taichung, Taiwan, 40440.
authors.forename: Chen-Huan
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Chung Y
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. johnyu@cgmh.org.tw.|Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan. johnyu@cgmh.org.tw.
authors.forename: John
authors.initials: J
authors.lastname: Yu
authors.affiliation: Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. chhsiehcmu@mail.cmu.edu.tw.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Hsieh
authors.affiliation: Translational Research Center, and Department of Neurology, China Medical University Hospital, Taichung, Taiwan, 40440. shyu9423@gmail.com.|Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. shyu9423@gmail.com.
authors.forename: Woei-Cherng
authors.initials: WC
authors.lastname: Shyu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003782:Dental Pulp / Q000378:metabolism* / Q000637:transplantation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000096:biosynthesis*
chemical_list: C583557:IGF1 protein, human; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Human dental pulp mesenchymal stem cells (hDSCs); Insulin-like growth factor 1 (IGF1); Insulin-like growth factor 1 receptor (IGF1R); Neonatal hypoxia-ischemia model; Neuroplasticity