Arterial endothelium creates a permissive niche for expansion of human cord blood hematopoietic stem and progenitor cells

• Main Authors: Huilin Li, Haiyun Pei, Sihan Wang, Bowen Zhang, Zeng Fan, Yiming Liu, Xiaoyan Xie, Zhou Yang, Lei Xu, Yali Jia, Yun Bai, Yi Han, Lin Chen, Lijuan He, Xue Nan, Wen Yue, Xuetao Pei
• Format: Article
• Language: English
• Published: BMC 2020-08-01
• Series: Stem Cell Research & Therapy
• Subjects: Arterial endothelial cells; Hematopoietic stem and progenitor cells; Expansion; Niche; Transplantation
• Online Access: http://link.springer.com/article/10.1186/s13287-020-01880-8

Abstract Background Although cord blood (CB) offers promise for treatment of patients with high-risk hematological malignancies and immune disorders, the limited numbers of hematopoietic stem cell (HSC)/progenitor cell in a CB unit and straitened circumstances in expanding ex vivo make it quite challenging to develop the successful cell therapies. Methods In this study, a novel strategy has been developed to support ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) by coculture with engineered human umbilical arterial endothelial cells (HuAECs-E4orf1-GFP), which expresses E4ORF1 stably by using a retroviral system. Results Coculture of CD34+ hCB cells with HuAECs-E4orf1-GFP resulted in generation of considerably more total nucleated cells, CD34+CD38−, and CD34+CD38−CD90+ HSPCs in comparison with that of cytokines alone or that of coculture with human umbilical vein endothelial cells (HuVECs) after 14-day amplification. The in vitro multilineage differentiation potential and in vivo repopulating capacity of the expanded hematopoietic cells cocultured with HuAECs-E4orf1-GFP were also markedly enhanced compared with the other two control groups. DLL4, a major determinant of arterial endothelial cell (EC) identity, was associated with CD34+ hCB cells amplified on HuAECs-E4orf1-GFP. Conclusions Collectively, we demonstrated that HuAECs acted as a permissive niche in facilitating expansion of HSPCs. Our study further implicated that the crucial factors and related pathways presented in HuAECs may give a hint to maintain self-renewal of bona fide HSCs.