title: Early senescence is not an inevitable fate of human-induced pluripotent stem-derived cells.
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.
authors: Department of Disease Control, National Center for Global Health and Medicine, Tokyo, Japan.
authors: Maiko
authors: M
authors: Gokoh
authors: Miwako
authors: M
authors: Nishio
authors: Naoko
authors: N
authors: Nakamura
authors: Satoko
authors: S
authors: Matsuyama
authors: Masako
authors: M
authors: Nakahara
authors: Shinnosuke
authors: S
authors: Suzuki
authors: Masami
authors: M
authors: Mitsumoto
authors: Hidenori
authors: H
authors: Akutsu
authors: Akihiro
authors: A
authors: Umezawa
authors: Kazuki
authors: K
authors: Yasuda
authors: Akira
authors: A
authors: Yuo
authors: Kumiko
authors: K
authors: Saeki
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D018920:Coculture Techniques / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology; D061252:Feeder Cells / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*