Nicotinamide adenine dinucleotide rejuvenates septic bone marrow mesenchymal stem cells  

作　　者：Xin Xia Kun Zhou Lin-Ying An Min Zhao Bin-Le Tian Jin-Yan Zhao Zhi-Gang Zhou Yin Tong 

机构地区：[1]Department of Hematology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China [2]Cancer Center,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China [3]Department of Laboratory Medicine,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China [4]Department of Critical Care Medicine,School of Medicine,Shanghai Jiao Tong University,Shanghai 201620,China

出　　处：《World Journal of Stem Cells》2025年第2期53-67,共15页世界干细胞杂志(英文)

基　　金：Shanghai Natural Science Foundation,No.21ZR1452300;the Clinical Research Innovation Plan of Shanghai General Hospital,No.CCTR-2022B04.

摘　　要：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 usingβ-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.

关 键 词：SEPSIS Bone mesenchymal stem cells Hematopoietic stem cells SENESCENCE Nicotinamide adenine dinucleotide 

分 类 号：R686.1[医药卫生—骨科学] R318.08[医药卫生—外科学]