Low oxygen tension favored expansion and hematopoietic reconstitution of CD34+ CD38- cells expanded from human cord blood-derived CD34+ Cells

被引:5
作者
Wang, Ziyan [1 ]
Du, Zheng [1 ]
Cai, Haibo [1 ]
Ye, Zhaoyang [1 ]
Fan, Jinli [1 ]
Tan, Wen-Song [1 ]
机构
[1] East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China
关键词
CD34(+)CD38(-)cells; Ex vivo expansion; Hematopoietic reconstitution; NOD; SCID mice; Oxygen tension; SCID-REPOPULATING CELLS; HUMAN BONE-MARROW; STEM-CELLS; EX-VIVO; HUMAN MEGAKARYOCYTES; IN-VITRO; MAINTENANCE; DIFFERENTIATION; HYPOXIA; PROLIFERATION;
D O I
10.1002/biot.201500497
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Oxygen tension is an important factor that regulates hematopoietic stem cells (HSCs) in both in vivo hematopoietic microenvironment and ex vivo culture system. Although the effect of oxygen tension on ex vivo expansion of HSCs was extensively studied, there were no clear descriptions on physiological function and gene expression analysis of HSCs under different oxygen tensions. In this study, the effects of oxygen tension on ex vivo expansion characteristics of human umbilical cord blood (UCB)-derived CD34(+) cells are evaluated. Moreover, the physiological function of expanded CD34(+) cells was assessed by secondary expansion ability ex vivo and hematopoietic reconstitution ability in vivo. Also, genetic profiling was applied to analyze the expression of genes related to cell function. It was found that low oxygen tension favored expansion of CD34(+)CD38(-) cells. Additionally, CD34(+) cells expanded under low oxygen tension showed better secondary expansion ability and reconstitution ability than those under atmospheric oxygen concentration. Finally, the genetic profiling of CD34(+)CD38(-) cells cultured under low oxygen tension was more akin to freshly isolated cells. These results collectively demonstrate that low oxygen tension was able to better maintain both self-renewal and hematopoietic reconstitution potential and may lay an experimental basis for clinical transplantation of HSCs.
引用
收藏
页码:945 / 953
页数:9
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