Induced pluripotent stem cells derived from human amnion in chemically defined conditions

Cell Cycle. 2018;17(3):330-347. doi: 10.1080/15384101.2017.1403690. Epub 2018 Feb 7.

Abstract

Fetal stem cells are a unique type of adult stem cells that have been suggested to be broadly multipotent with some features of pluripotency. Their clinical potential has been documented but their upgrade to full pluripotency could open up a wide range of cell-based therapies particularly suited for pediatric tissue engineering, longitudinal studies or disease modeling. Here we describe episomal reprogramming of mesenchymal stem cells from the human amnion to pluripotency (AM-iPSC) in chemically defined conditions. The AM-iPSC expressed markers of embryonic stem cells, readily formed teratomas with tissues of all three germ layers present and had a normal karyotype after around 40 passages in culture. We employed novel computational methods to determine the degree of pluripotency from microarray and RNA sequencing data in these novel lines alongside an iPSC and ESC control and found that all lines were deemed pluripotent, however, with variable scores. Differential expression analysis then identified several groups of genes that potentially regulate this variability in lines within the boundaries of pluripotency, including metallothionein proteins. By further studying this variability, characteristics relevant to cell-based therapies, like differentiation propensity, could be uncovered and predicted in the pluripotent stage.

Keywords: CellNet; PluriTest; RNA sequencing; amnion; episomal reprogramming; iPSC; microarray.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amnion / cytology*
  • Biomarkers / metabolism
  • Cell Shape
  • Cells, Cultured
  • Gene Regulatory Networks
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Teratoma / pathology
  • Transcription, Genetic

Substances

  • Biomarkers

Grant support

This work was supported by the Fonds Medizinische Forschung at the University of Zurich, Forschungskredit of the University of Zurich, The Swiss Society of Cardiology, The Swiss National Science Foundation under Grant [320030-122273] and [310030-143992], The 7th Framework Programme, Life Valve, European Commission under Grant [242008], the Olga Mayenfisch Foundation, the EMDO Foundation, the Start-up Grant 2012 of the University Hospital Zurich, Foundation of Scientific Research Zurich [STWF-17-013], and internal funding of the Mitchell Cancer Institute.