Generation and genetic modification of induced pluripotent stem cells

Expert Opin Biol Ther. 2010 Jul;10(7):1089-103. doi: 10.1517/14712598.2010.496775.

Abstract

Importance of the field: The generation of induced pluripotent stem cells (iPSCs) enabled by exogenous expression of the canonical Oct4, Sox2, Klf4 and c-Myc reprogramming factors has opened new ways to create patient- or disease-specific pluripotent cells. iPSCs represent an almost inexhaustible source of cells for targeted differentiation into somatic effector cells and hence are likely to be invaluable for therapeutic applications and disease-related research.

Areas covered in this review: After an introduction on the biology of reprogramming we cover emerging technological advances, including new reprogramming approaches, small-molecule compounds and tailored genetic modification, and give an outlook towards potential clinical applications of iPSCs.

What the reader will gain: Although this field is progressing rapidly, reprogramming is still an inefficient process. The reader will learn about innovative tools to generate patient-specific iPSCs and how to modify these established lines in a safe way. Ideally, the disease-causing mutation is edited directly in the genome using novel technologies based on artificial nucleases, such as zinc-finger nucleases.

Take home message: Human iPSCs create fascinating options with regard to disease modeling, drug testing, developmental studies and therapeutic applications. However, important hurdles have to be taken and more efficient protocols to be established to achieve the ambitious goal of bringing iPSCs into clinical use.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle / genetics
  • Cell Differentiation / genetics
  • Cell Proliferation
  • Esterases / genetics
  • Esterases / metabolism
  • Gene Expression Regulation, Developmental* / drug effects
  • Gene Transfer Techniques
  • Genetic Therapy / methods
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / physiology*
  • Induced Pluripotent Stem Cells / transplantation
  • Kruppel-Like Factor 4
  • Stem Cell Transplantation
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Zinc Fingers

Substances

  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Transcription Factors
  • Esterases