Transcending the Cell Fate Stereotype: Cell Penetrating Peptide Technology helps Induce Pluripotency in Multiple Cell Types

Induced pluripotent stem cells (iPSCs) are one of the most promising new technologies in the field of regenerative medicine. iPSCs can be generated directly from a patient’s own fibroblast cells then converted into any cell type, thus overcoming challenges associated with embryonic stem cells and graft-vs-host disease that result from current methods. Generation of iPSCs from fibroblasts is traditionally accomplished by ectopic expression of four key transcription factors (TFs): Oct4, Sox2, Klf4, and c-Myc also known as OSKM. These TFs have been shown to be involved in maintaining pluripotency and inhibiting embryonic stem (ES) cell differentiation. Reprogramming fibroblasts into iPSCs is most efficiently accomplished by viral introduction of the four TFs using lentivirus systems. However, these mechanisms are problematic owing to the possible integration of foreign DNA into cells and subsequent tumorigenic effects. Direct delivery of reprogramming factor proteins via cell penetrating peptides (CPPs) overcomes these issues, however, endosomal entrapment commonly results in inefficient cargo delivery. These reprogramming protocols produce inefficient results that lack the propensity to be translated into direct patient therapy, ultimately negating the purpose of iPSC creation. However, the creation of a novel CPP-adapter system has bypassed the problem associated with traditional CPP delivery and provides a better route for reprogramming that may be more suitable for personalized therapeutics