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Oxid Med Cell Longev. 2019 Nov 18;2019:5153268. doi: 10.1155/2019/5153268. eCollection 2019.

Reactive Oxygen Species and Nrf2: Functional and Transcriptional Regulators of Hematopoiesis.

Hu L#1,2,3, Zhang Y#1,2,3, Miao W1,2,3, Cheng T1,2,3,4,5.

Author information

1
State Key Laboratory of Experimental Hematology, China.
2
National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, China.
3
Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
4
Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Tianjin, China.
5
Department of Stem Cell & Regenerative Medicine, Peking Union Medical College, Tianjin, China.
#
Contributed equally

Abstract

Hematopoietic stem cells (HSCs) are characterized by self-renewal and multilineage differentiation potentials. Although they play a central role in hematopoietic homeostasis and bone marrow (BM) transplantation, they are affected by multiple environmental factors in the BM. Here, we review the effects of reactive oxygen species (ROS) and Nrf2 on HSC function and BM transplantation. HSCs reside in the hypoxic microenvironment of BM, and ROS play an important role in HSPC regulation. Recently, an extraphysiologic oxygen shock/stress phenomenon was identified in human cord blood HSCs collected under ambient air conditions. Moreover, Nrf2 has been recently recognized as a master transcriptional factor that regulates multiple antioxidant enzymes. Since several years, the role of Nrf2 in hematopoiesis has been extensively studied, which has functional similarities of cellular oxygen sensor hypoxia-inducible factor-1 as transcriptional factors. Increasing evidence has revealed that abnormally elevated ROS production due to factors such as genetic defects, aging, and ionizing radiation unexceptionally resulted in lethal impairment of HSC function and hematopoiesis. Both experimental and clinical studies have identified elevated ROS levels as a major culprit of ineffective BM transplantation. Lastly, we discuss the possibility of using small molecule antioxidants, such as N-acetyl cysteine, resveratrol, and curcumin, to augment HSC function and improve the therapeutic efficacy of BM transplantation. Further research on the function of ROS levels and improving the efficacy of BM transplantation may have a great potential for broad clinical applications of HSCs.

Conflict of interest statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

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