Miniature-swine iPSC-derived GABA progenitor cells function in a rat Parkinson ’s disease model

AbstractInduced pluripotent stem cells (iPS cells) are considered a promising source of cell-based therapy for the treatment of Parkinson ’s disease (PD). Recent studies have shown forebrain GABA interneurons have crucial roles in many psychiatric disorders, and secondary changes in the GABA system play a directly effect on the pathogenesis of PD. Here, we first describe an efficient differentiation procedure of GABA progenitors (Mi PSC-iGABAPs) from miniature-swine iPSCs through two major developmental stages. Then, the MiPSC-iGABAPs were stereotactically transplanted into the right medial forebrain bundle (MFB) of 6-hydroxydopamine (OHDA)-lesioned PD model rats to confirm their feasibility for the neural transplantation as a donor material. Furthermore, the grafted MiPSC-iGABAPs could survive and migrate from the graft site into the surrounding brain tissue including striatum (ST) and substantia nigra (SN) for at least 32 weeks, and significantly improved functional recovery of PD rats from their parkinsonian behaviora l defects. Histological studies showed that the grafted cells could migrate and differentiate into various neurocytes, including GABAergic, dopaminergic neurons, and glial cells in vivo, and many induced dopaminergic neurons extended dense neurites into the host striatum. Moreover, over 50% of the g rafted MiPSC-iGABAPs could express GABA, and these GABAergic neurons might be responsible for modifying the balance of excitatory and inhibitory signals in the...
Source: Cell and Tissue Research - Category: Cytology Source Type: research