Published online Feb 26, 2024. doi: 10.4252/wjsc.v16.i2.163
Peer-review started: October 18, 2023
First decision: December 2, 2023
Revised: December 14, 2023
Accepted: January 12, 2024
Article in press: January 12, 2024
Published online: February 26, 2024
Processing time: 130 Days and 18.6 Hours
The in vitro expansion strategy of increasing the number of hematopoietic stem cells (HSCs) in cord blood is expected to improve its clinical efficacy. Nicotinamide (NAM) is one of the small molecules that can promote the expansion of he
The effects of different concentrations of NAM on proliferation and differentiation of HSCs, as well as whether it affects sirtuin 1 (SIRT1) transcription levels, have not been reported. There are various small molecule substances used for in vitro culture of HSCs (including UM171, SR1, VPA, NAM and ID8), which may affect the maintenance, proliferation, differentiation and homing of HSCs by regulating different pathways, and different molecular pathways may have synergistic effects. This study aimed to provide a theoretical basis for the future joint application of multiple small mo
To evaluate the effects and mechanisms of different concentrations of NAM on HSC proliferation and differentiation.
In this study, we added different concentrations of NAM to serum-free culture medium inoculated with CD34+ cells. We then measure the number, molecular phenotype, cycle distribution, and apoptosis of each group of cells and explore the mechanism by detecting the levels of reactive oxygen species (ROS), inflammatory factors and related gene transcription.
We evaluated the expansion efficiency of different concentrations of NAM on HSPCs, ST-HSCs as well as LT-HSCs, and the results showed that 5 mmol/L and 10 mmol/L NAM were beneficial for maintaining HSPCs, with low concentrations (5 mmol/L) of NAM being more conducive to ST-HSCs expansion, while high concentrations (10 mmol/L) of NAM had a more significant effect on promoting LT-HSCs expansion. Low concentrations of NAM can better regulate the balance between proliferation and differentiation, thereby promoting effective expansion of HSCs.
Low concentration of NAM did not inhibit but upregulated the transcription of SIRT1, promoting cell proliferation by activating the SIRT1–HIF1A pathway, delaying stem cell differentiation by increasing ROS clearance, and ultimately promoting effective expansion of HSCs.
Drugs that specifically target LT-HSCs or ST-HSCs may help in the development of tailored HSC grafts that either fa