Pluripotent Stem Cells from Neuronal Cells

Inventors: Maria C. N. Marchetto, Alysson R. Muotri & Fred H. Gage
Potential Uses: CNS, Drug Discovery, Gene Expression, Research Tool, Stem Cells

Figure 1. Schematic model of virus-free human iPS generation from neural stem cells

Genetic reprogramming of somatic cells to a pluripotent state (induced pluripotent stem or iPS cells) by over-expression of specific genes has been accomplished using mouse and human cells. Resultant iPS cells are isogenic to the donor individual, i.e., carrying similar genetic background, and are useful for a potential therapeutic purpose with lower risk of immune rejection as well as applicable to understand complex diseases with heritable and sporadic conditions.

Currently, there are several obstacles before iPS cells might be considered for cellular therapy, such as the use of oncogenes and insertional mutagenesis by delivery viruses that may induce malignant cell transformation. Here we describe the generation of human iPS cells without viral vectors and the first transcriptional profile of a "footprint-free" iPS cells. Pluripotent factors Oct4 and Nanog were cloned in episomal vectors and transfected into Sox2 and c-Myc expressing human fetal neural progenitor cells. The transient expression of these two factors resulted in highly efficient generation of human iPS cells without evidence of vector integration. Our method represents a safe way to generate human iPS cells for clinical purposes and basic research.