(Introduction)
Many stroke and neurotrauma patients remain permanently disabled and require definitive placement either in a nursing home or an assisted living environment, with great economic and social consequences. Recent advances in stem cell biology have raised expectations that diseases and injuries of the CNS may be ameliorated by the delivery stem cell-based therapeutics. This study is aimed at investigating the characteristics of human iPS cell (iPSC)-derived cortical neurons after transplantation of them into the brain of adult rats.
The questions are as follows: (1)Are human iPSC-derived cortical neurons survive in the adult brain? (2)How far do the grafted neurons extend neurites in the corticospinal tract? (3)What properties do the grafted neurite-projecting neurons have?
(Materials & Methods)
Human iPSCs were cultured for 48 days to differentiate into cortical neuronal precursors by using quick aggregation method(Eiraku et al., 2008). The cells were maintained in the form of spheres. And we transplanted the spheres to the motor cortex of X-SCID adult male rats weighing 170-250g. Eight weeks after transplantation, we injected retrograde fluorescent neuronal tracer(Fast Blue) into their corticospinal tract. Then, they were perfused transcardially with 4% paraformaldehyde 3 days after tracer injection.
(Result)
(1)Human iPSC-derived cortical neurons survived in the brain of adult rats.
(2)The grafted neurons extended neurites in the CST to the pyramidal decussation.
(3)The protein CTIP2 was positive in the grafted neurons projecting neurites to the corticospinal tract.