Targeted migration and differentiation of engrafted neural precursor cells in amyloid β-treated hippocampus in rats

Abstract

Objective: To observe the migration and differentiation of the neural precursor cells (NPCs) that derived from murine embryonic stem cells (ESCs) when they were transplanted into amyloid β (Aβ)-treated rat hippocampus. Methods: MESPU35, a murine ESC cell line that express the enhanced green fluorescent protein (EGFP), was induced differentiation into nestin-positive NPCs by modified serum-free methods. The Aβ plaques and the differentiation of the grafted cells were observed by immunofluorescent staining. Results: Comparing 16 weeks with 4 weeks post-transplantation, the migration distance increased about 5 times; the rate of migratory NPCs differentiating into glial fibrillary acidic protein (GFAP)-positive cells kept rising from (30.41±1.45)% to (49.25±1.23)%, and the rate of NPCs differentiating into neurofilament 200 (NF200) positive cells increased from (16.68±0.95)% to (27.94±1.21)%. Meanwhile, the GFAP-positive cells targeting to the ipsilateral side of Aβ plaques increased from 60.2% to 81.3%, while the NF200-positive cells increased from 61.3% to 84.1%. The migration distance had significant positive linear correlations to the neuronal differentiation rate (r = 0.991) and to the astrocytic differentiation rate (r = 0.953). Conclusion: Engrafted NPCs migrate targetedly to the Aβ injection site and differentiate into neurons and astrocytes.