Mesenchymal stem cells (MSCs) undergo a decline in function following ex vivo expansion and exposure to irradiation. This has been associated with accumulation of DNA damage and has important implications for tissue engineering approaches or in @entity1 receiving radiotherapy. Therefore, interventions, which limit accumulation of DNA damage in MSC, are of clinical significance. We were intrigued by findings showing that @entity4381 ( @entity5921 ), an anti-resorptive @entity1568 containing @entity5520 , significantly extended survival in @entity1 affected by @entity170 . The effect was too large to be simply due to the prevention of @entity174 . Moreover, in combination with @entity6817 , it extended the lifespan in a @entity19 model of @entity14697 . Therefore, we asked whether @entity5921 was able to extend the lifespan of @entity1 MSC and whether this was due to reduced accumulation of DNA damage, one of the important mechanisms of aging. Here, we show that this was the case both following expansion and irradiation, preserving their ability to proliferate and differentiate in vitro. In addition, administration of @entity5921 before irradiation protected the survival of mesenchymal progenitors in @entity19 . Through mechanistic studies, we were able to show that inhibition of @entity3470 signaling, a pathway involved in longevity and @entity5 , was responsible for these effects. Our data open up new opportunities to protect MSC from the side effects of radiotherapy in @entity5 @entity1 and during ex vivo expansion for regenerative medicine approaches. Given that @entity5921 is already in clinical use with a good safety profile, these opportunities can be readily translated for @entity1 benefit. Stem Cells 2016;34:756-767.

XXXX Attenuates Accumulation of DNA Damage in Mesenchymal Stem Cells and Protects Their Function.

@entity1 :: ('9606', 'Species') :: ['human', 'patients', 'patient'] @entity5921 :: ('CHEBI:46557', 'Chemical') :: ['ZOL'] @entity1568 :: ('MESH:D009584', 'Chemical') :: ['nitrogen'] @entity174 :: ('MESH:D050723', 'Disease') :: ['fractures'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity170 :: ('MESH:D010024', 'Disease') :: ['osteoporosis'] @entity5520 :: ('D004164', 'Chemical') :: ['bisphosphonate'] @entity3470 :: ('21977(Tax:10090)', 'Gene') :: ['mTOR'] @entity14697 :: ('MESH:D011371', 'Disease') :: ['Hutchinson Gilford Progeria Syndrome'] @entity4381 :: ('MESH:C088658', 'Chemical') :: ['zoledronate'] @entity6817 :: ('D019821', 'Chemical') :: ['statins']
@entity4381 :: (MESH:C088658,Chemical) :: ['Zoledronate']
