Transgene expression in various organs post BM-HSC transplantation.
Transgene expression in various organs post BM-HSC transplantation.
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DOI：
10.1016/j.scr.2013.10.010
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发表时间：
2014-01
影响因子：
1.2
通讯作者：
Mellins, Elizabeth D.
中科院分区：
文献类型：
--
作者：
Wang, Nan;Rajasekaran, Narendiran;Hou, Tieying;Mellins, Elizabeth D.
骨髓源性造血干细胞（BM-HSC）介导的基因治疗已被广泛用于治疗临床前和临床环境中的遗传缺陷。使用有丝分裂失活的细胞靶向慢病毒，其具有针对我们感兴趣的基因（鼠MHC II类（MHCII）伴侣蛋白，不变链（Ii））的单独启动子和GFP报告基因，我们监测了在来自不同器官（脾、胰腺淋巴结（PLN）、BM和血液）的各种类型的专职抗原呈递细胞（B细胞、巨噬细胞和DC）中引入的Ii的表达和功能。检测Ii和GFP。Ii水平仅在来自脾的巨噬细胞和单核细胞、来自PLN的单核细胞和来自血液的巨噬细胞前体中与GFP水平相关。根据细胞类型，PLN细胞中的Ii水平与脾细胞中的Ii水平比血液或BM细胞中的Ii水平更相似。在功能上，在PLN或脾中表达的Ii比在BM或血液中表达的Ii对MHCII丰度有更大的影响。这些结果对分析同时引入治疗基因和报告基因的基因治疗的结果具有一定的意义。这些发现也对理解免疫分子功能的发展具有意义。
Gene therapy mediated by bone marrow-derived hematopoietic stem cells (BM-HSC) has been widely used in treating genetic deficiencies in both pre-clinical and clinical settings. Using mitotically inactive cell-targeting lentivirus with separate promoters for our gene of interest (the murine MHC class II (MHCII) chaperone, invariant chain (Ii)) and a GFP reporter, we monitored the expression and function of introduced Ii in various types of professional antigen presenting cells (B cells, macrophages and DC) from different organs (spleen, pancreatic lymph nodes (PLN), BM and blood). Ii and GFP were detected. Ii levels correlated with GFP levels only in macrophages and monocytes from spleen, monocytes from PLN and macrophage precursors from blood. By cell type, Ii levels in PLN cells were more similar to those in spleen cells than to those in blood or BM cells. Functionally, Ii expressed in PLN or spleen had more effect on MHCII abundance than Ii expressed in BM or blood. The results have implications for analysis of the outcomes of gene therapy when both therapeutic and reporter genes are introduced. The findings also have implications for understanding the development of immune molecule function.
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