Umbilical cord blood-derived neutrophils possess higher viability than peripheral blood derived neutrophils

Qi Liu; Yuliang Wu; Genyin Chen; Jiaqing Li; Yingying Chen; Yao Ge; Chunyan Wang; Bing Xiong; Dandan Chen; Xuguang Wang; Shupeng Liu; Zhongping Cheng

doi:10.62347/HQIP2227

Umbilical cord blood-derived neutrophils possess higher viability than peripheral blood derived neutrophils

Am J Cancer Res. 2024 Mar 15;14(3):1190-1203. doi: 10.62347/HQIP2227. eCollection 2024.

Authors

Qi Liu^{1

2}, Yuliang Wu^{1

2}, Genyin Chen^{3

4}, Jiaqing Li¹, Yingying Chen¹, Yao Ge^{1

2}, Chunyan Wang¹, Bing Xiong¹, Dandan Chen¹, Xuguang Wang^{3

4}, Shupeng Liu^{1

2}, Zhongping Cheng^{1

2}

Affiliations

¹ Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.
² Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine Shanghai 200072, China.
³ Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University Zhanjiang 524001, Guangdong, China.
⁴ Clinical Research Center, Guangdong Medical University Zhanjiang 524001, Guangdong, China.

Abstract

Neutrophils, a primary type of immune cell, play critical roles in numerous biological processes. Both umbilical cord blood (UCB) and peripheral blood are rich in neutrophils. UCB is more abundant than peripheral blood, with cells generally at a more immature stage. However, comparative data between these two cell sources is lacking. This study aims to elucidate differences between UCB-derived neutrophils (UCBN) and peripheral blood-derived neutrophils (PBN). UCBN and PBN were isolated from fresh human umbilical cord blood and peripheral blood, respectively. Transcriptomic profiling was performed and compared against neutrophil RNA from three different donors. Bioinformatics analysis was employed to compare cell phenotypes. A cytokine cocktail (IFN-β, IFN-γ, and LPS) was used to activate UCBN and PBN in vitro. A united multi-omic approach, combining transcriptomic and proteomic analysis, was followed by experimental validation through flow cytometry, cell killing assays, and proteome profiler array to verify cell functions. Transcriptomic analysis revealed that the most upregulated genes in freshly isolated umbilical cord blood neutrophils (UCBN) compared to peripheral blood neutrophils (PBN) predominantly involve neutrophil activation and cell-killing functions. Validation through flow cytometry and cell-killing experiments demonstrated that highly viable UCBN exhibited significantly stronger ovarian tumor cell-killing activity in vitro compared to PBN. Both transcriptomic and proteomic analyses indicated that the primary upregulated genes in activated UCBN are chiefly involved in biological processes related to the regulation of cytokine secretion. Integrative multi-omic analysis, including a proteome profiler array, confirmed that UCBN indeed secrete elevated levels of cytokines. In conclusion: UCBN shows higher viability and cellular activity compared with PBN, particularly in tumor cell-killing and cytokine secretion.

Keywords: Neutrophils; peripheral blood; umbilical cord blood; viability.