PMID- 24659476
OWN - NLM
STAT- MEDLINE
DCOM- 20151007
LR  - 20211203
IS  - 1549-4918 (Electronic)
IS  - 1066-5099 (Linking)
VI  - 32
IP  - 8
DP  - 2014 Aug
TI  - Inhibition of Akt/mTOR attenuates age-related changes in mesenchymal stem cells.
PG  - 2256-66
LID - 10.1002/stem.1709 [doi]
AB  - The decline in mesenchymal stem cell (MSC) self-renewal and function with aging 
      contributes to diseases associated with impaired osteogenesis. MSC donor age in 
      prolonged culture also limits the therapeutic potential of these cells for tissue 
      engineering and regenerative medicine. Here, we demonstrate an intervention to 
      preserve the immature state MSC and consequently maintain self-renewal and 
      differentiation capacity during in vitro aging. We showed that blocking of 
      phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) prevents 
      the development of an age-related phenotype and maintains MSC morphology of early 
      passage cells with high clonogenic frequency and enhanced proliferative capacity. 
      MSC cultured in the presence of inhibitors of Akt or mTOR also robustly maintain 
      their osteogenic potential, that is otherwise lost during in vitro aging. We 
      further report that these effects may be mediated by induction of expression of 
      pluripotency genes Nanog and Oct-4 and by the reduction in the production of 
      cytoplasmic reactive oxygen species (ROS). Additionally, loss of Akt/mTOR and ROS 
      was accompanied with lower levels of DNA damage. These results provide an insight 
      into mechanisms involved in MSC aging and suggest possible interventions to 
      maintain quiescence and function of MSC prior to in vivo transplantation or as 
      pharmacological agents in diseases associated with loss of MSC function.
CI  - (c) 2014 AlphaMed Press.
FAU - Gharibi, Borzo
AU  - Gharibi B
AD  - Department of Periodontology, Dental Institute, King's College London, Tower 
      Wing, Guy's Hospital, London, United Kingdom.
FAU - Farzadi, Samira
AU  - Farzadi S
FAU - Ghuman, Mandeep
AU  - Ghuman M
FAU - Hughes, Francis J
AU  - Hughes FJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Blotting, Western
MH  - Cell Differentiation/*physiology
MH  - Cellular Senescence/*physiology
MH  - Comet Assay
MH  - DNA Damage/physiology
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Young Adult
OTO - NOTNLM
OT  - Aging
OT  - Akt
OT  - Mammalian target of rapamycin
OT  - Mesenchymal stem cell
OT  - Rapamycin
OT  - Self-renewal
EDAT- 2014/03/25 06:00
MHDA- 2015/10/08 06:00
CRDT- 2014/03/25 06:00
PHST- 2013/10/30 00:00 [received]
PHST- 2014/02/01 00:00 [accepted]
PHST- 2014/03/25 06:00 [entrez]
PHST- 2014/03/25 06:00 [pubmed]
PHST- 2015/10/08 06:00 [medline]
AID - 10.1002/stem.1709 [doi]
PST - ppublish
SO  - Stem Cells. 2014 Aug;32(8):2256-66. doi: 10.1002/stem.1709.