Suematsu Sachiko, Watanabe Takeshi
Research Unit for Immune Surveillance, RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.
Nat Biotechnol. 2004 Dec;22(12):1539-45. doi: 10.1038/nbt1039. Epub 2004 Nov 28.
Stromal cells play an important role in the formation of the normal organized microarchitecture of secondary lymphoid organs. Here we demonstrate that a tissue-engineered, lymphoid tissue-like organoid, which was constructed by transplantation of stromal cells embedded in biocompatible scaffolds into the renal subcapsular space in mice, had an organized tissue structure similar to secondary lymphoid organs. This organoid contained compartmentalized B-cell and T-cell clusters, high endothelial venule-like vessels, germinal centers and follicular dendritic cell networks. Furthermore, the organoid was transplantable to naive normal or severe combined immunodeficiency (SCID) mice, and antigen-specific, IgG-isotype antibody formation could be induced soon after intravenous administration of the antigen. This simplified system of lymphoid tissue-like organoid construction will facilitate analyses of cell-cell interactions required for development of secondary lymphoid organs and efficient induction of adaptive immune responses, and may have possible applications in the treatment of immune deficiency.
基质细胞在次级淋巴器官正常有序微结构的形成中发挥着重要作用。在此，我们证明，通过将包埋于生物相容性支架中的基质细胞移植到小鼠肾被膜下间隙构建的组织工程化类淋巴组织类器官，具有与次级淋巴器官相似的组织结构。该类器官包含分隔的B细胞和T细胞簇、高内皮微静脉样血管、生发中心和滤泡树突状细胞网络。此外，该类器官可移植到未接触过抗原的正常或严重联合免疫缺陷（SCID）小鼠体内，静脉注射抗原后不久即可诱导抗原特异性IgG同种型抗体的形成。这种简化的类淋巴组织类器官构建系统将有助于分析次级淋巴器官发育所需的细胞间相互作用以及适应性免疫反应的有效诱导，并且可能在免疫缺陷治疗中具有潜在应用。
