Sublethal heat shock induces premature senescence rather than apoptosis in human mesenchymal stem cells.
Stem cells in adult organism are responsible for cell turnover and tissue regeneration. The study of stem cell stress response contributes to our knowledge on the mechanisms of damaged tissue repair. Previously, we demonstrated that sublethal heat shock (HS) induced apoptosis in human embryonic stem cells. This study aimed to investigate HS response of human adult stem cells. Human mesenchymal stem cells (MSCs) cultivated in vitro were challenged with sublethal HS. It was found that sublethal HS did not affect the cell viability assessed by annexin V/propidium staining. However, MSCs subjected to severe HS exhibited features of stress-induced premature senescence (SIPS): irreversible cell cycle arrest, altered morphology, increased expression of senescence-associated β-galactosidase (SA-β-gal) activity, and induction of cyclin-dependent kinase inhibitor p21 protein. High level of Hsp70 accumulation induced by sublethal HS did not return to the basal level, at least, after 72 h of the cell recovery when most cells exhibited SIPS hallmarks. MSCs survived sublethal HS, and resumed proliferation sustained the properties of parental MSCs: diploid karyotype, replicative senescence, expression of the cell surface markers, and capacity for multilineage differentiation. Our results showed for the first time that in human MSCs, sublethal HS induced premature senescence rather than apoptosis or necrosis. MSC progeny that survived sublethal HS manifested stem cell properties of the parental cells: limited replicative life span and multilineage capacity.
Larisa L
LL
Alekseenko
Victoria I
VI
Zemelko
Alisa P
AP
Domnina
Olga G
OG
Lyublinskaya
Valery V
VV
Zenin
Nataly A
NA
Pugovkina
Irina V
IV
Kozhukharova
Alexandra V
AV
Borodkina
Tatiana M
TM
Grinchuk
Irina I
II
Fridlyanskaya
Nikolay N
NN
Nikolsky
D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D019070:Cell Lineage; D002470:Cell Survival; D016922:Cellular Senescence; D005434:Flow Cytometry; D018869:Heat-Shock Response; D006801:Humans; D007621:Karyotyping; D059630:Mesenchymal Stem Cells / Q000166:cytology*