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用白细胞介素-7基因转导的骨髓基质细胞共移植可增强小鼠异基因骨髓移植后的免疫重建。

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

作者信息

Li A, Zhang Q, Jiang J, Yuan G, Feng Y, Hao J, Li C, Gao X, Wang G, Xie S

机构信息

Department of Immunology, Peking University Health Center, Beijing, People's Republic of China.

出版信息

Gene Ther. 2006 Aug;13(15):1178-87. doi: 10.1038/sj.gt.3302741. Epub 2006 Apr 6.

DOI:10.1038/sj.gt.3302741
PMID:16598299
Abstract

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.

摘要

异基因骨髓移植(allo-BMT)后会经历一段严重免疫缺陷期,这导致机体对感染高度易感,并限制了该方法在临床上的广泛应用。在此,我们使用腺病毒载体将人白细胞介素-7(IL-7)基因转导至供体来源的骨髓基质细胞(MSC)中,并将这种基因工程化的MSC(MSC-IL-7)移植到经致死剂量照射的C57BL/6小鼠体内,以研究其对allo-BMT后免疫重建的影响。接受MSC-IL-7细胞加BALB/c小鼠去除T细胞的骨髓细胞的受体小鼠,其胸腺生成和外周T淋巴细胞的稳态扩增显著增加。此外,allo-BMT后注射MSC-IL-7细胞可保护宿主免受急性移植物抗宿主病(GVHD)致死,并防止移植T细胞诱导的GVHD发生。因此,使用MSC-IL-7细胞可能在治疗上有助于增强allo-BMT小鼠的免疫重建,而不加重GVHD。

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