Automated, High-Throughput Derivation, Characterization and Differentiation of Induced Pluripotent Stem Cells

Nat Methods. 2015 Sep;12(9):885-92. doi: 10.1038/nmeth.3507. Epub 2015 Aug 3.

Abstract

Induced pluripotent stem cells (iPSCs) are an essential tool for modeling how causal genetic variants impact cellular function in disease, as well as an emerging source of tissue for regenerative medicine. The preparation of somatic cells, their reprogramming and the subsequent verification of iPSC pluripotency are laborious, manual processes limiting the scale and reproducibility of this technology. Here we describe a modular, robotic platform for iPSC reprogramming enabling automated, high-throughput conversion of skin biopsies into iPSCs and differentiated cells with minimal manual intervention. We demonstrate that automated reprogramming and the pooled selection of polyclonal pluripotent cells results in high-quality, stable iPSCs. These lines display less line-to-line variation than either manually produced lines or lines produced through automation followed by single-colony subcloning. The robotic platform we describe will enable the application of iPSCs to population-scale biomedical problems including the study of complex genetic diseases and the development of personalized medicines.

Publication types

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

MeSH terms

  • Batch Cell Culture Techniques / instrumentation*
  • Cell Differentiation / physiology
  • Cell Separation / instrumentation*
  • Cells, Cultured
  • Equipment Design
  • Equipment Failure Analysis
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / physiology*
  • Microfluidic Analytical Techniques / instrumentation*
  • Robotics / instrumentation*