PMID- 23998797
OWN - NLM
STAT- MEDLINE
DCOM- 20140828
LR  - 20181217
IS  - 1557-8534 (Electronic)
IS  - 1547-3287 (Linking)
VI  - 23
IP  - 1
DP  - 2014 Jan 1
TI  - Differentiation potential and profile of nuclear receptor expression during 
      expanded culture of human adipose tissue-derived stem cells reveals PPARgamma as an 
      important regulator of Oct4 expression.
PG  - 24-33
LID - 10.1089/scd.2013.0137 [doi]
AB  - Potential therapeutic use of human adipose tissue-derived stem cells (hADSCs) 
      requires the production of large cell numbers by in vitro expansion. However, 
      long-term in vitro culture is associated with reduced stem cell characteristics 
      and differentiation capability. We investigated the proliferation rate and 
      expression of p16(INK4a) mRNA, surface stem cell markers, and stem cell 
      transcription factors. The proliferation rate decreased significantly as passages 
      increased, and the expression of p16(INK4a) mRNA significantly increased. FACS 
      analysis of CD73, CD90, and CD105 expression showed no significant difference 
      among examined passages; however, the mRNA expression levels of pluripotent 
      markers, Oct4 and Nanog, were significantly decreased at higher passages. At 
      passages 12 and 20, there was decreased differentiation capability into 
      insulin-producing cells, evidenced by significantly decreased expression of 
      insulin and related beta cell markers. Adipogenic and osteogenic differentiation was 
      also decreased at higher passages. We then analyzed the transcriptional 
      expression profiles of 48 nuclear receptors at four different passages. We found 
      that the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and 
      thyroid hormone receptor TRbeta was significantly decreased at higher passages. 
      Treatment with PPARgamma activators or overexpression of PPARgamma in hADSCs at passage 
      20 could recover Oct4 expression levels and increase Oct4 promoter activity. 
      PPARgamma inactivation by GW9662 inhibited the troglitazone-induced Oct4 mRNA 
      expression. Furthermore, PPARgamma overexpression in hADSC at passage 20 improved the 
      differentiation potential to insulin-producing cells. In conclusion, we 
      demonstrated that hADSCs undergo characteristic changes and reduction of 
      differentiation capability during expanded culture in vitro, and revealed the 
      role of PPARgamma as one potential factor in the regulation of Oct4 expression during 
      in vitro aging of hADSCs.
FAU - Dao, Lan T M
AU  - Dao LT
AD  - 1 College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon 
      University , Incheon, South Korea .
FAU - Park, Eun-Young
AU  - Park EY
FAU - Hwang, Ok-Kyung
AU  - Hwang OK
FAU - Cha, Ji-Young
AU  - Cha JY
FAU - Jun, Hee-Sook
AU  - Jun HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131004
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (2-chloro-5-nitrobenzanilide)
RN  - 0 (Anilides)
RN  - 0 (Biomarkers)
RN  - 0 (Chromans)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Insulin)
RN  - 0 (NANOG protein, human)
RN  - 0 (Nanog Homeobox Protein)
RN  - 0 (Octamer Transcription Factor-3)
RN  - 0 (POU5F1 protein, human)
RN  - 0 (PPAR gamma)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Thiazolidinediones)
RN  - 0 (Thyroid Hormone Receptors beta)
RN  - I66ZZ0ZN0E (Troglitazone)
SB  - IM
MH  - Adipose Tissue/*cytology
MH  - Aging/physiology
MH  - Anilides/pharmacology
MH  - Biomarkers
MH  - Cell Culture Techniques
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cell- and Tissue-Based Therapy
MH  - Cells, Cultured
MH  - Chromans/pharmacology
MH  - Cyclin-Dependent Kinase Inhibitor p16/genetics
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Developmental
MH  - Homeodomain Proteins/biosynthesis
MH  - Humans
MH  - Insulin/biosynthesis/metabolism
MH  - Insulin Secretion
MH  - Insulin-Secreting Cells/cytology
MH  - Nanog Homeobox Protein
MH  - Octamer Transcription Factor-3/*biosynthesis/genetics
MH  - PPAR gamma/antagonists & inhibitors/biosynthesis/*genetics
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Cytoplasmic and Nuclear/biosynthesis
MH  - Stem Cells/*cytology
MH  - Thiazolidinediones/pharmacology
MH  - Thyroid Hormone Receptors beta/biosynthesis
MH  - Troglitazone
EDAT- 2013/09/04 06:00
MHDA- 2014/08/29 06:00
CRDT- 2013/09/04 06:00
PHST- 2013/09/04 06:00 [entrez]
PHST- 2013/09/04 06:00 [pubmed]
PHST- 2014/08/29 06:00 [medline]
AID - 10.1089/scd.2013.0137 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2014 Jan 1;23(1):24-33. doi: 10.1089/scd.2013.0137. Epub 2013 Oct 
      4.