Cultured Cells from the Human Oocyte Cumulus Niche Are Efficient Feeders to Propagate Pluripotent Stem Cells

Stem Cells Dev. 2015 Oct 1;24(19):2317-27. doi: 10.1089/scd.2015.0043. Epub 2015 Jul 8.

Abstract

Pluripotency is at the crossroads of stem cell research and biology of reproduction. The mature metaphase II oocyte contains the key factors for pluripotency induction and maintenance as assessed by its capacity to reprogram somatic nuclei. The cumulus cells (CCs) niche that surrounds the oocyte is crucial for its maturation and presumably for the oocyte to acquire its competence to confer pluripotency. In this study, we examined whether cells cultured from the human mature metaphase II oocyte CC niche (hCC) could be used as feeders for the propagation of human induced pluripotent stem cells. The induced pluripotent (iPS) cells cultured on hCC (hCC-iPS) were assessed for their pluripotency potential by their expression of pluripotency-associated genes such as Oct4, Nanog, and TRA1-60 and their competence to differentiate into the three germ layers in vitro (embryoid bodies) as well as in vivo (teratoma formation). We show that not only the hCC-iPS cells maintained their pluripotency potential, but they also exhibited much better self-renewal performance in terms of proliferation rate compared to the same cells cultured on human foreskin fibroblast (hFF) feeders (hFF-iPS). A comparative gene expression profile study of hCC and hFF revealed significant differences (P < 0.05) in expression of cellular matrix components and an upregulation in hCC of genes known to be important players in cell proliferation such as interleukin 6 gene (IL6).

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation*
  • Cells, Cultured
  • Coculture Techniques
  • Cumulus Cells / cytology*
  • Cumulus Cells / metabolism
  • Embryoid Bodies / cytology
  • Embryoid Bodies / metabolism
  • Epithelial Cell Adhesion Molecule
  • Feeder Cells / cytology*
  • Feeder Cells / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Homeodomain Proteins / genetics
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / metabolism
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3 / genetics
  • Oocytes / cytology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Teratoma / genetics
  • Teratoma / metabolism
  • Teratoma / pathology
  • Transplantation, Heterologous
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule
  • Homeodomain Proteins
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Vimentin