PMID- 28337294
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 9
IP  - 2
DP  - 2017
TI  - Hypoxic preconditioning of human cardiosphere-derived cell sheets enhances 
      cellular functions via activation of the PI3K/Akt/mTOR/HIF-1alpha pathway.
PG  - 664-673
AB  - Cell sheet technology is a promising therapeutic strategy for the treatment of 
      ischemic diseases such as myocardial infarction. We recently developed a novel 
      protocol, termed "hypoxic preconditioning," capable of augmenting the therapeutic 
      efficacy of cell sheets. Following this protocol, the pro-angiogenic and 
      anti-fibrotic activity of cell sheets were enhanced by brief incubation of cell 
      sheets under hypoxic culture conditions. However, the precise molecular mechanism 
      underlying the hypoxic preconditioning of cell sheets is unclear. In the present 
      study, we examined signal transducers in cell sheets to identify those responsive 
      to hypoxic preconditioning, using cardiosphere-derived cell (CDC) sheets. We 
      initially tested whether sheet-like structures were suitable for hypoxic 
      preconditioning by comparing them with individual cells. Hypoxic preconditioning 
      was more effective in sheeted cells than in individual cells. Expression of 
      hypoxia inducible factor-1alpha (HIF-1alpha) and mammalian target of rapamycin (mTOR) 
      were induced upon hypoxic preconditioning of cell sheets, as was the 
      phosphoinositide 3-kinase (PI3K)/Akt pathway. In addition, hypoxic 
      preconditioning increased phosphorylation of epidermal growth factor receptor 
      (EGFR) and heat shock protein 60 (HSP60) in CDC sheets. Our findings provide 
      novel insights into the utility of hypoxic preconditioning in cell sheet-based 
      technologies for the treatment of ischemic diseases.
FAU - Tanaka, Yuya
AU  - Tanaka Y
AD  - Department of Surgery and Clinical Science, Graduate School of Medicine, 
      Yamaguchi University 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
FAU - Hosoyama, Tohru
AU  - Hosoyama T
AD  - Department of Surgery and Clinical Science, Graduate School of Medicine, 
      Yamaguchi University1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan; Center 
      for Regenerative Medicine, Graduate School of Medicine, Yamaguchi University1-1-1 
      Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
FAU - Mikamo, Akihito
AU  - Mikamo A
AD  - Department of Surgery and Clinical Science, Graduate School of Medicine, 
      Yamaguchi University 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
FAU - Kurazumi, Hiroshi
AU  - Kurazumi H
AD  - Department of Surgery and Clinical Science, Graduate School of Medicine, 
      Yamaguchi University1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan; 
      Department of Surgery, Saiseikai Yamaguchi Hospital2-11 Midoricho, Yamaguchi, 
      Yamaguchi 753-8517, Japan.
FAU - Nishimoto, Arata
AU  - Nishimoto A
AD  - Department of Surgery and Clinical Science, Graduate School of Medicine, 
      Yamaguchi University 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
FAU - Ueno, Koji
AU  - Ueno K
AD  - Department of Surgery and Clinical Science, Graduate School of Medicine, 
      Yamaguchi University 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
FAU - Shirasawa, Bungo
AU  - Shirasawa B
AD  - Department of Surgery and Clinical Science, Graduate School of Medicine, 
      Yamaguchi University 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
FAU - Hamano, Kimikazu
AU  - Hamano K
AD  - Department of Surgery and Clinical Science, Graduate School of Medicine, 
      Yamaguchi University 1-1-1 Minami-kogushi, Ube, Yamaguchi 755-8505, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170215
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC5340701
OTO - NOTNLM
OT  - Cell sheet
OT  - HIF-1alpha
OT  - cardiosphere
OT  - hypoxic preconditioning
EDAT- 2017/03/25 06:00
MHDA- 2017/03/25 06:01
PMCR- 2017/02/15
CRDT- 2017/03/25 06:00
PHST- 2016/09/23 00:00 [received]
PHST- 2016/12/27 00:00 [accepted]
PHST- 2017/03/25 06:00 [entrez]
PHST- 2017/03/25 06:00 [pubmed]
PHST- 2017/03/25 06:01 [medline]
PHST- 2017/02/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2017 Feb 15;9(2):664-673. eCollection 2017.