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Int J Mol Sci. 2019 Apr 23;20(8). pii: E1985. doi: 10.3390/ijms20081985.

Liver Sinusoidal Endothelial Cells Promote the Expansion of Human Cord Blood Hematopoietic Stem and Progenitor Cells.

Li H1, Pei H2,3, Xie X4,5, Wang S6,7, Jia Y8,9, Zhang B10,11, Fan Z12, Liu Y13,14, Bai Y15, Han Y16, He L17,18, Nan X19,20, Yue W21,22, Pei X23,24.

Author information

1
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. ice199303@163.com.
2
Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing 100850, China. peihy@hotmail.com.
3
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. peihy@hotmail.com.
4
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. alpha13@126.com.
5
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. alpha13@126.com.
6
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. wangsihan_lk@hotmail.com.
7
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. wangsihan_lk@hotmail.com.
8
Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing 100850, China. yaly_bio@163.com.
9
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. yaly_bio@163.com.
10
Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing 100850, China. fish_zbw1985@163.com.
11
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. fish_zbw1985@163.com.
12
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. fan17930@yeah.net.
13
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. liuym07@126.com.
14
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. liuym07@126.com.
15
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. josephinebyzy@163.com.
16
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. yemuhan@163.com.
17
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. hlj821@163.com.
18
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. hlj821@163.com.
19
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. diamond_girl263@126.com.
20
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. diamond_girl263@126.com.
21
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. wenyue226@126.com.
22
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. wenyue226@126.com.
23
Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China. peixt@nic.bmi.ac.cn.
24
South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China. peixt@nic.bmi.ac.cn.

Abstract

Cord blood (CB) is an attractive source of hematopoietic stem cells (HSCs) for hematopoietic cell transplantation. However, its application remains limited due to the low number of HSCs/progenitors in a single CB unit and its notoriously difficulty in expanding ex vivo. Here, we demonstrated that the human fetal liver sinusoidal endothelial cells engineered to constitutively express the adenoviral E4orf1 gene (hFLSECs-E4orf1) is capable of efficient expansion ex vivo for human CB hematopoietic stem and progenitor cells (HSPCs). Coculture of CD34+ hCB cells with hFLSECs-E4orf1 resulted in generation of substantially more total nucleated cells, CD34+CD38- and CD34+ CD38-CD90+ HSPCs in comparison with that of cytokines alone after 14 days. The multilineage differentiation potential of the expanded hematopoietic cells in coculture condition, as assessed by in vitro colony formation, was also significantly heightened. The CD34+ hCB cells amplified on hFLSECs-E4orf1 were capable of engraftment in vivo. Furthermore, hFLSECs-E4orf1 highly expressed hematopoiesis related growth factor and Notch receptors. Accordingly, the CD34+ hCB cells amplified on hFLSECs-E4orf1 exhibited Notch signaling activation. Taken together, our findings indicated that FLSECs may potentially be the crucial component of the microenvironment to support recapitulation of embryonic HSC amplification in vitro and allow identification of new growth factors responsible for collective regulation of hematopoiesis.

KEYWORDS:

expansion; hematopoietic stem and progenitor cells; liver sinusoidal endothelial cells; microenvironment; transplantation

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