Co-transplantation of bone marrow stromal cells transduced with IL-7 gene enhances immune reconstitution after allogeneic bone marrow transplantation in mice

被引:24
|
作者
Li, A. [1 ]
Zhang, Q. [1 ]
Jiang, J. [1 ]
Yuan, G. [1 ]
Feng, Y. [1 ]
Hao, J. [1 ]
Li, C. [1 ]
Gao, X. [1 ]
Wang, G. [1 ]
Xie, S. [1 ]
机构
[1] Peking Univ, Ctr Hlth, Dept Immunol, Beijing 100083, Peoples R China
基金
中国国家自然科学基金;
关键词
allogeneic bone marrow transplantation; adenovirus vectors; interleukin-7; immune reconstitution; graft-versus-host disease;
D O I
10.1038/sj.gt.3302741
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Allogeneic bone marrow transplantation (allo-BMT) is followed by a period of profound immune deficiency, which results in significant susceptibility to infections and limits the extensive application of this approach in clinic. Here, we transduced human interleukin-7 (IL-7) gene into donor-derived bone marrow stromal cells (MSCs) using adenovirus vector, and transplanted this gene-engineered MSCs (MSC-IL-7) into lethally irradiated C57BL/ 6 mice to investigate their effects on immune reconstitution following allo-BMT. Recipient mice receiving MSC-IL-7 cells plus T-cell-depleted bone marrow cells of BALB/ c mice showed a significant increase in thymopoiesis and homeostatic expansion of peripheral T lymphocytes. Furthermore, injection of MSC-IL-7 cells following allo-BMT protected the host from the lethality caused by acute graft-versus-host disease (GVHD) and prevented the occurrence of GVHD induced by transplanted T cells. Thus, the use of MSC-IL-7 cells may be therapeutically useful for enhancing immune reconstitution without aggravating GVHD in allo-BMT mice.
引用
收藏
页码:1178 / 1187
页数:10
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