TGF-? Signaling Accelerates Senescence of Human Bone-Derived CD271 and SSEA-4 Double-Positive Mesenchymal Stromal Cells.

ABSTRACT: It is generally thought that the proliferative capacity and differentiation potential of somatic stem cells, including mesenchymal stromal/stem cells (MSCs) and hematopoietic stem cells, decline with age. We investigated the effects of aging on human bone-derived MSCs expressing CD271 and SSEA-4 (double-positive MSCs [DPMSCs]). The percentages of DPMSCs in bone tissue decreased significantly with age. The DPMSCs from elderly patients (old DPMSCs) showed cellular senescence, which was evidenced by low growth potential, high senescence-associated ?-galactosidase activity, and elevated p16 and p21 CDK inhibitor levels. Moreover, old DPMSCs showed weak osteogenic differentiation potential and less hematopoiesis-supporting activity in comparison with young DPMSCs. Interestingly, the addition of transforming growth factor ?2 (TGF-?2) induced cellular senescence in young DPMSCs. With the exception of the adipogenic differentiation potential, all of the aging phenomena observed in old DPMSCs were reversed by the addition of anti-TGF-? antibodies. These results suggest that, in part, old DPMSCs accelerate cellular senescence through TGF-? signaling.

SUBMITTER: Kawamura H 

PROVIDER: S-EPMC5918367 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature