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IGF1R+ Dental Pulp Stem Cells Enhanced Neuroplasticity in Hypoxia-Ischemia Model
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IGF1R+ Dental Pulp Stem Cells Enhanced Neuroplasticity in Hypoxia-Ischemia Model

Hsiao-Yu Chiu, Chen-Huan Lin, Chung Y. Hsu, John Yu, Chia-Hung Hsieh 和 Woei-Cherng Shyu
Molecular neurobiology, 卷.54(10), 頁碼.8225-8241
01/12/2017
PMID: 27914008
Web of Science ID: WOS:000415341900056

摘要

Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Science & Technology
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.

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