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BACKGROUND

News — Sepsis is a severe illness characterized by systemic and multiorgan reactive responses and damage. However, the impact of sepsis on the bone marrow, particularly on bone marrow mesenchymal stem cells (BMSCs), is less reported. BMSCs are critical stromal cells in the bone marrow microenvironment that maintain bone stability and hematopoietic homeostasis; however, the impairment caused by sepsis remains unknown.

AIM

To investigate the effects of sepsis on BMSCs and the underlying mechanisms.

METHODS

BMSCs were obtained from healthy donors and patients with sepsis. We compared the self-renewal capacity, differentiation potential, and hematopoietic supportive ability in vitro. Senescence of septic BMSCs was assessed using β-galactosidase staining, senescence-associated secretory phenotype, intracellular reactive oxygen species levels, and the expression of P16 and P21. Finally, the changes in septic BMSCs after nicotinamide adenine dinucleotide (NAD) treatment were evaluated.

RESULTS

Septic BMSCs showed decreased proliferation and self-renewal, bias towards adipogenic differentiation, and weakened osteogenic differentiation. Additionally, hematopoietic supportive capacity declines in sepsis. The levels of aging markers were significantly higher in the septic BMSCs. After NAD treatment, the proliferation capacity of septic BMSCs showed a recovery trend, with increased osteogenic and hematopoietic supportive capacities. Sepsis resulted in decreased expression of sirtuin 3 (SIRT3) in BMSCs, whereas NAD treatment restored SIRT3 expression, enhanced superoxide dismutase enzyme activity, reduced intracellular reactive oxygen species levels, maintained mitochondrial stability and function, and ultimately rejuvenated septic BMSCs.

CONCLUSION

Sepsis accelerates the aging of BMSCs, as evidenced by a decline in self-renewal and osteogenic capabilities, as well as weakened hematopoietic support functions. These deficiencies can be effectively reversed via the NAD/SIRT3/superoxide dismutase pathway.

Core Tip: Sepsis often leads to multiorgan dysfunction, including damage to bone marrow mesenchymal stem cells (BMSCs). This damage accelerates the aging of BMSCs, resulting in impaired self-renewal and differentiation abilities and weakened hematopoietic support functions. These changes disrupt hematopoiesis and may even cause long-term immunosuppression and bone loss. Nicotinamide adenine dinucleotide, which protects mitochondrial function, can rejuvenate septic BMSCs and provide a new target for adjunctive therapy to control post-sepsis complications.

• Citation: Xia X, Zhou K, An LY, Zhao M, Tian BL, Zhao JY, Zhou ZG, Tong Y. Nicotinamide adenine dinucleotide rejuvenates septic bone marrow mesenchymal stem cells. World J Stem Cells 2025; 17(2): 96893
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