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 language | English |
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Pages (from-to) | 8225-8241 |
Number of pages | 17 |
Journal | Molecular Neurobiology |
Volume | 54 |
Issue number | 10 |
DOIs | |
State | Published - 01 12 2017 |
Externally published | Yes |
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