Interleukin-12 supports in vitro self-renewal of long-term hematopoietic stem cells  

作　　者：Shanshan Zhang Maiko Morita Zhao Wang Jun Ooehara Sen Zhang Miner Xie Haitao Bai Wenying Yu Xiaofang Wang Fang Dong Jinhong Wang Shihui Ma Satoshi Yamazaki Hideo Ema 

机构地区：[1]Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin,China [2]Project Division of Advanced Regenerative Medicine,Institute of Medical Science,University of Tokyo,Tokyo,Japan [3]Laboratory of Stem Cell Therapy,Center for Experimental Medicine,Institute of Medical Science,University of Tokyo,Tokyo,Japan

出　　处：《Blood Science》2019年第1期92-101,共10页血液科学（英文）

基　　金：supported by grants from the National Key Research and Development Program of China Stem Cell and Translational Research(2017YFA0104903,2016YFA0100600,and 2017YFA0103400);the Ministry of Science and Technology of China(2015CB964403 and,2011CB964801);the CAMS Initiative for Innovative Medicine(2016-I2M-1-017 and 2017-I2M-1-015);the National Natural Science Foundation of China(81470279,81670105,81421002,81400077,and 81500085).

摘　　要：Hematopoietic stem cells(HSCs)self-renew or differentiate through division.Cytokines are essential for inducing HSC division,but the optimal cytokine combination to control self-renewal of HSC in vitro remains unclear.In this study,we compared the effects of interleukin-12(IL-12)and thrombopoietin(TPO)in combination with stem cell factor(SCF)on in vitro self-renewal of HSCs.Single-cell assays were used to overcome the heterogeneity issue of HSCs,and serum-free conditions were newly established to permit reproduction of data.In single-cell cultures,CD150^(+)CD48^(-)CD41^(-)CD34^(-)c-Kit^(+)Sca-1^(+)lineage^(-)SCs divided significantly more slowly in the presence of SCF+IL-12 compared with cells in the presence of SCF+TPO.Serial transplantation of cells from bulk and clonal cultures revealed that TPO was more effective than IL-12 at supporting in vitro self-renewal of short-term(<6 months)HSCs,resulting in a monophasic reconstitution wave formation,whereas IL-12 was more effective than TPO at supporting the in vitro selfrenewal of long-term(>6 months)HSCs,resulting in a biphasic reconstitution wave formation.The control of division rate in HSCs appeared to be crucial for preventing the loss of self-renewal potential from their in vitro culture.

关 键 词：Ex vivo expansion Hematopoietic stem cells INTERLEUKIN-12 SELF-RENEWAL 

分 类 号：R57[医药卫生—消化系统]