Development of Next-generation Tumor-homing Induced Neural Stem Cells to Enhance Treatment of Metastatic Cancers

Engineered tumor-homing neural stem cells (NSCs) have shown promise in treating cancer. Recently, we transdifferentiated skin fibroblasts into tumor-homing early-stage human induced NSCs (hiNSC) as personalized NSC drug carriers. Here, using a SOX2 and spheroidal culture-based reprogramming strategy, we generated a new hiNSC variant, hiNeuroS, that were genetically distinct from fibroblasts and first-generation hiNSCs and possessed significantly enhanced tumor-homing and anti-tumor properties. To understand the transcriptomic profile of cells during our sphere-based generation of hiNeuroS, we performed single-cell RNA sequencing (scRNA-seq). The results showed that, while some of the hiNeuroS cells shared a similar trajectory states with the fibroblasts, there was a unique cell group at the far end of hiNeuroS trajectory towards the latest pseudotime, and suggested our new sphere-based culture methods generate hiNeuroS that are a genetically distinct NSC sub-populations that expresses tumor-homing pathways at levels greater than hiNSC. Single-cell RNA-seq profiles of hiNeuroS-TRAIL, hiNSC-GFP-TRAIL, and NHF-1 cells were generated by deep sequencing using 10x Genomics Chromium System.