Therapeutic function of a novel rat induced pluripotent stem cell line in a 6‑OHDA‑induced rat model of Parkinson's disease.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder of the central nervous system that results from the loss of dopaminergic (DA) nigral neurons. Induced pluripotent stem cells (iPSCs) have shown potential for cell transplantation treatment of neurodegenerative disorders. In the present study, the small molecules CHIR99021 and RepSox (CR) significantly facilitated reprogramming and enhanced the efficiency of GFP+/iPS‑like colonies [rat iPSCs induced by OCT3/4, Sox2, Klf4, c‑Myc, Nanog and Lin28 + CR (RiPSCs‑6F/CR)] generation by ~4.0‑fold during lentivirus‑mediated reprogramming of six transcription factors in rat embryonic fibroblasts. The generation of iPSCs was detected by reverse transcription‑PCR, immunofluorescence and western blot analysis. Subsequently, RiPSCs‑6F/CR were stereotactically transplanted into the right medial forebrain bundle (MFB) of 6‑hydroxydopamine‑lesioned rats with PD. The transplanted RiPSCs‑6F/CR survived and functioned in the MFB of rats with PD for ≥20weeks, and significantly improved functional restoration from their PD‑related behavioral defects. Furthermore, the grafted RiPSCs‑6F/CR could migrate and differentiate into various neurocytes invivo, including γ aminobutyric acid‑ergic, DA neurons and glial cells. In conclusion, the present study confirmed that RiPSCs‑6F/CR induced by small molecules could be used as potential donor material for neural grafting to remodel basal ganglia circuitry in neurodegenerative diseases.