TY - JOUR
T1 - Detection of mesenchymal stem cells senescence by prelamin A accumulation at the nuclear level
AU - Bellotti, Chiara
AU - Capanni, Cristina
AU - Lattanzi, Giovanna
AU - Donati, Davide
AU - Lucarelli, Enrico
AU - Duchi, Serena
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background: Human mesenchymal stem cells (MSC), during in vitro expansion, undergo a progressive loss of proliferative potential that leads to the senescent state, associated with a reduction of their “medicinal” properties. This may hampers their efficacy in the treatment of injured tissues. Quality controls on MSC-based cell therapy products should include an assessment of the senescent state. However, a reliable and specific marker is still missing. From studies on lamin-associated disorders, has emerged the correlation between defective lamin A maturation and cellular senescence. Findings: Primary cultured hMSC lines (n = 3), were analyzed by immunostaining at different life-span stages for the accumulation of prelamin A, along with other markers of cellular senescence. During culture, cells at the last stage of their life span displayed evident signs of senescence consistent with the positivity of SA-β-gal staining. We also observed a significant increase of prelamin A positive cells. Furthermore, we verified that the cells marked by prelamin A were also positive for p21Waf1 while negative for Ki67. Conclusions: Overall data support that the detection of prelamin A identifies senescent MSC, providing an easy and reliable tool to be use alone or in combination with known senescence markers to screen MSC before their use in clinical applications.
AB - Background: Human mesenchymal stem cells (MSC), during in vitro expansion, undergo a progressive loss of proliferative potential that leads to the senescent state, associated with a reduction of their “medicinal” properties. This may hampers their efficacy in the treatment of injured tissues. Quality controls on MSC-based cell therapy products should include an assessment of the senescent state. However, a reliable and specific marker is still missing. From studies on lamin-associated disorders, has emerged the correlation between defective lamin A maturation and cellular senescence. Findings: Primary cultured hMSC lines (n = 3), were analyzed by immunostaining at different life-span stages for the accumulation of prelamin A, along with other markers of cellular senescence. During culture, cells at the last stage of their life span displayed evident signs of senescence consistent with the positivity of SA-β-gal staining. We also observed a significant increase of prelamin A positive cells. Furthermore, we verified that the cells marked by prelamin A were also positive for p21Waf1 while negative for Ki67. Conclusions: Overall data support that the detection of prelamin A identifies senescent MSC, providing an easy and reliable tool to be use alone or in combination with known senescence markers to screen MSC before their use in clinical applications.
KW - Cell- and tissue-based therapy
KW - Lamin A
KW - Mesenchymal stem cells
KW - Prelamin A
KW - Senescence
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UR - http://www.scopus.com/inward/citedby.url?scp=84984664018&partnerID=8YFLogxK
U2 - 10.1186/s40064-016-3091-7
DO - 10.1186/s40064-016-3091-7
M3 - Article
AN - SCOPUS:84984664018
VL - 5
JO - SpringerPlus
JF - SpringerPlus
SN - 2193-1801
IS - 1
M1 - 1427
ER -