Effective ex vivo expansion of hematopoietic stem cells using osteoblast-differentiated mesenchymal stem cells is CXCL12 dependent

被引:51
|
作者
Mishima, Seiji [2 ]
Nagai, Atsushi [1 ]
Abdullah, Sk [1 ]
Matsuda, Chikashi [2 ]
Taketani, Takeshi [3 ]
Kumakura, Shunichi [4 ]
Shibata, Hiroshi [2 ]
Ishikura, Hiroto [5 ]
Kim, Seung U. [6 ,7 ]
Masuda, Junichi [1 ]
机构
[1] Shimane Univ, Dept Lab Med, Fac Med, Izumo, Shimane 6938501, Japan
[2] Shimane Univ Hosp, Cent Clin Lab, Izumo, Shimane, Japan
[3] Shimane Univ Hosp, Div Blood Transfus, Vancouver, BC, Canada
[4] Shimane Univ, Fac Med, Dept Educ Rural Med, Vancouver, BC, Canada
[5] Shimane Univ Hosp, Ctr Canc, Vancouver, BC, Canada
[6] Univ British Columbia, UBC Hosp, Div Neurol, Vancouver, BC V5Z 1M9, Canada
[7] Chung Ang Univ, Coll Med, Med Res Inst, Seoul 156756, South Korea
关键词
ex vivo expansion; hematopoietic stem cell; mesenchymal stem cell; osteoblast; CXCL12; HUMAN BONE-MARROW; CORD BLOOD-CELLS; CD34(+) CELLS; PROGENITOR CELLS; FACTOR-I; ENGRAFTMENT; CHEMOKINES; CULTURE; RECONSTITUTION; MAINTENANCE;
D O I
10.1111/j.1600-0609.2010.01419.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Effective ex vivo expansion of hematopoietic stem cells (HSCs) is a prerequisite for HSC transplantation. Growth and maintenance of HSC is dependent on cytokine and niche factors. We investigated whether mesenchymal stem cells (MSCs) or osteogenic cytokine-differentiated MSCs play a role in HSC expansion. We used the human HM3.B10 (B10) MSC cell line and the osteoblast-differentiated B10 (Ost-B10) as a feeder layer and examined ex vivo expansion of CD34+CD38- HSCs obtained from peripheral blood (PB) and cord blood (CB) with or without several growth cytokines. Both undifferentiated B10 and Ost-B10 cells exhibited similar effects on total HSC expansion; however, Ost-B10 demonstrated a higher potency in CD34+CD38- cell-specific proliferation in the presence of cytokines compared to undifferentiated B10 HSCs. Colony-forming cell assay and long-term culture initiating cell assay revealed that Ost-B10 displayed multipotent differentiation and enabled long-term ex vivo culture of HSCs. We next examined the relationship between HSC expansion and the presence of various chemokines. CXCL4 and CXCL12 expression were increased in Ost-B10 cells compared with the B10 cells. CD34+CD38- cells were significantly increased with CXCL12, but not CXCL4 treatment. siRNA inhibition of CXCL12 decreased CXCL12 secretion in both B10 and Ost-B10, whereas expansion of CD34+CD38- cells was decreased in Ost-B10 alone. These results demonstrated that ex vivo expansion of HSCs may be highly effective through osteoblast-differentiated MSCs acting as a feeder layer, and likely operates through the CXCL12 chemokines signaling pathway.
引用
收藏
页码:538 / 546
页数:9
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