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 [PMID: 40061269 DOI: 10.4252/wjsc.v17.i2.96893]
Corresponding Author of This Article
Yin Tong, PhD, Professor, Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China. 18616909158@163.com
Research Domain of This Article
Hematology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Stem Cells. Feb 26, 2025; 17(2): 96893 Published online Feb 26, 2025. doi: 10.4252/wjsc.v17.i2.96893
Nicotinamide adenine dinucleotide rejuvenates septic bone marrow mesenchymal stem cells
Xin Xia, Kun Zhou, Lin-Ying An, Min Zhao, Bin-Le Tian, Jin-Yan Zhao, Zhi-Gang Zhou, Yin Tong
Xin Xia, Kun Zhou, Lin-Ying An, Min Zhao, Yin Tong, Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Bin-Le Tian, Cancer Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Jin-Yan Zhao, Department of Laboratory Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
Zhi-Gang Zhou, Department of Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai 201620, China
Co-first authors: Xin Xia and Kun Zhou.
Co-corresponding authors: Zhi-Gang Zhou and Yin Tong.
Author contributions: Zhou ZG and Tong Y contributed to the funding acquisition, writing - review & editing and supervision of this manuscript, they contributed equally to this manuscript as co-corresponding authors; Xia X and Zhou K took part in the investigation and visualization, manuscript writing - original draft, they contributed equally to this manuscript as co-first authors; An LY and Zhao M participated in collect samples; Tian BL contributed to the data visualization and interpretation of this manuscript; An LY, Zhao M, and Zhao JY participated in the resources of this study.
Supported by Shanghai Natural Science Foundation, No. 21ZR1452300; and the Clinical Research Innovation Plan of Shanghai General Hospital, No. CCTR-2022B04.
Institutional review board statement: This study was approved by the institutional review board of Shanghai General Hospital, No. [2023]145.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data were available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yin Tong, PhD, Professor, Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China. 18616909158@163.com
Received: May 17, 2024 Revised: November 19, 2024 Accepted: January 16, 2025 Published online: February 26, 2025 Processing time: 282 Days and 20.4 Hours
Abstract
BACKGROUND
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.
