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

Abstract

Summary: 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. : Sonoda et al. established bone-derived CD271+SSEA-4+ MSCs (DPMSCs) from young and elderly patients and demonstrated that DPMSCs may accelerate cellular senescence through TGF-β2 signaling. TGF-β can change the balance of adipogenesis and osteogenesis of DPMSCs. As a result, it may influence the impaired hematopoiesis observed in elderly patients. Interestingly, the aging phenomena can possibly be reversed by anti-TGF-β antibodies. Keywords: MSC, TGF-β, aging, senescence, HSC, rejuvenation, human bone