J Tissue Eng Regen Med. 2019 May 31. doi: 10.1002/term.2904. [Epub ahead of print]

Improved neural differentiation of normal and abnormal iPSC lines in the presence of valproic acid.

Fernandes S¹, Vinnakota R², Kumar J², Kale V^1,3, Limaye L¹.

Abstract

During the generation of induced pluripotent stem cell (iPSC) lines from cord blood CD34⁺ cells, a line having complete trisomy of chromosome 1 and deletion of q23 to qTer of chromosome 11 was accidentally developed in our lab. The abnormality was consistently detected even at higher passages. These chromosomal anomalies are known to manifest neurological developmental defects. In order to examine if such defects occur during in vitro differentiation of the cell line, we set up a protocol for neural differentiation. Valproic acid (VPA) was earlier reported by us to enhance neural differentiation of placental mesenchymal stem cells. Here we induced normal and abnormal iPSC lines to neural lineage with/without VPA. Neural differentiation was observed in all 4 sets, but for both the iPSCs lines, VPA sets performed better. The characteristics tested were morphology, neural filament length, detection of neural markers and electrophysiology. In summary, the karyotypically abnormal line exhibited efficient neural differentiation. This iPSC line may serve as a useful tool to study abnormalities associated with trisomy 1 and deletion of q23 to qTer of chromosome 11.