The reprogramming efficiency to iN cells varies substantially between cell types [21, 22, 30, 31, 36]. In particular human cells appear to be more resistant to iN cell reprogramming than their mouse counterparts [6, 28, 31, 36]. For example, the efficiencies of MEFs are around 20% whereas adult human fibroblasts are below 1%. There is also a developmental component with embryonic being more efficient than neonatal and neonatal being more efficient than adult fibroblasts. From a pragmatic point of view, skin-derived fibroblasts and fresh blood cells would represent ideal donor cell populations for reprogramming given the ease of access. Unfortunately, human blood cells appear to be even more refractory to iN cell reprogramming than adult dermal fibroblasts. Therefore, to improve iN cell reprogramming efficiencies of resistant cell types is one of the most critical issues to overcome before this technology can be used for translational use such as disease modeling of brain diseases using patient-derived cells. Similar efforts have been made for the iPS cell technology but their success is not so critical because typically only few iPS cell lines
