Stem Cell Research & Therapy (2020-08-01)

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

  • 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

DOI
https://doi.org/10.1186/s13287-020-01880-8
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 13

Abstract

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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.

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