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

Stem Cell Reports
Hiroshi KawamuraYoshiaki Sonoda

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 β-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 β2 (TGF-β2) 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-β antibodies. These results suggest that, in part, old DPMSCs accelerate cellular senescence through TGF-β signaling.

Citations

Nov 22, 2018·Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution·Xin-Xin ZhaoXue-Ming Zhang
Mar 29, 2019·Journal of Cellular and Molecular Medicine·Haiwei HeXin Li
Sep 19, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Sajjad AshrafRita Kandel
Oct 30, 2019·International Journal of Molecular Sciences·Kana Tominaga, Hiroshi I Suzuki
Oct 6, 2018·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Edgar Ledesma-MartínezEdelmiro Santiago-Osorio
Feb 8, 2020·Cells·Francisco Triana-MartínezEduardo Domínguez
Feb 16, 2021·Pharmacology & Therapeutics·Dingyu HuJi Zhang

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Datasets Mentioned

BETA
GSE101694

Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
ELISA
total hip replacement arthroplasty
Fluorescence-Activated Cell Sorting

Software Mentioned

FlowJo

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