Early senescence is not an inevitable fate of human-induced pluripotent stem-derived cells

Cell Reprogram. 2011 Aug;13(4):361-70. doi: 10.1089/cell.2011.0004. Epub 2011 Jun 30.

Abstract

Human-induced pluripotent stem cells (hiPSCs) are expected to become a powerful tool for regenerative medicine. Their efficacy in the use of clinical purposes is currently under intensive verification. It was reported that hiPSC-derived hemangioblasts had severely limited expansion capability due to an induction of early senescence: hiPSC-derived vascular endothelial cells (VECs) senesced after one passage and hiPSC-derived hematopoietic progenitor cells (HPCs) showed substantially decreased colony-forming activities. Here we show that early senescence is not an inevitable fate of hiPSC-derived cells. Applying our unique feeder-free culture methods for the differentiations of human embryonic stem cells (hESCs), we successfully generated VECs and HPCs from three lines of hiPSCs that were established by using a retrovirus vector system. All hiPS-derived VECs could be subcultured by 2:1∼3:1 dilutions up to 10∼20 passages, after which the cells underwent senescence. Among the three lines of hiPSCs, two lines generated HPCs that bore comparable granulocyte colony-forming units to those of hESCs. Moreover, one line effectively reproduced HPCs within the sac-like structures, the fields of in vitro hematopoiesis, as in the case of hESCs. Surprisingly, release of neutrophils into culture supernatant persisted even longer (∼60 days) than the case of hESCs (∼40 days). Thus, the problem of early senescence can be overcome by selecting appropriate lines of hiPSCs and applying proper differentiation methods to them.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques / methods*
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Cellular Senescence / physiology*
  • Coculture Techniques / methods
  • Endothelial Cells / cytology
  • Feeder Cells / cytology
  • Hematopoietic Stem Cells / cytology
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / physiology*