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, Woei Cherng Shyu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

18 Scopus citations

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.

Original languageEnglish
Pages (from-to)8225-8241
Number of pages17
JournalMolecular Neurobiology
Volume54
Issue number10
DOIs
StatePublished - 01 12 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016, Springer Science+Business Media New York.

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

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