Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells With Synthetic Modified mRNA

Cell Stem Cell. 2010 Nov 5;7(5):618-30. doi: 10.1016/j.stem.2010.08.012. Epub 2010 Sep 30.

Abstract

Clinical application of induced pluripotent stem cells (iPSCs) is limited by the low efficiency of iPSC derivation and the fact that most protocols modify the genome to effect cellular reprogramming. Moreover, safe and effective means of directing the fate of patient-specific iPSCs toward clinically useful cell types are lacking. Here we describe a simple, nonintegrating strategy for reprogramming cell fate based on administration of synthetic mRNA modified to overcome innate antiviral responses. We show that this approach can reprogram multiple human cell types to pluripotency with efficiencies that greatly surpass established protocols. We further show that the same technology can be used to efficiently direct the differentiation of RNA-induced pluripotent stem cells (RiPSCs) into terminally differentiated myogenic cells. This technology represents a safe, efficient strategy for somatic cell reprogramming and directing cell fate that has broad applicability for basic research, disease modeling, and regenerative medicine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects*
  • Cell Lineage
  • Cells, Cultured
  • Cellular Reprogramming / genetics*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / drug effects*
  • RNA, Messenger* / pharmacology

Substances

  • RNA, Messenger

Associated data

  • GEO/GSE23583