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通过植入藻酸盐包封细胞调节全身细胞因子水平。

Modulation of systemic cytokine levels by implantation of alginate encapsulated cells.

作者信息

Savelkoul H F, van Ommen R, Vossen A C, Breedland E G, Coffman R L, van Oudenaren A

机构信息

Department of Immunology, Erasmus University, Rotterdam, Netherlands.

出版信息

J Immunol Methods. 1994 Apr 15;170(2):185-96. doi: 10.1016/0022-1759(94)90394-8.

DOI:10.1016/0022-1759(94)90394-8
PMID:8157997
Abstract

The availability of cell lines that are transfected with IL-4, IL-5 and IFN-gamma cytokine genes permits the prolonged in vivo delivery of functional cytokines in relatively large doses for the modulation of specific immune responses. Often the transfected cells are xenogeneic or allogeneic to the experimental animal and have to be encapsulated in such a way that no cellular response by the host will be induced. Alginate has proven to be a simple matrix for encapsulating cells under mild conditions suitable for in vivo implantation. Encapsulated cells express the transfected IL-4 gene for at least 14 days after in vivo implantation and were shown to be functional during that period by modulating ongoing IgE responses. The application of adherent growing transfected cells permits dose-response titrations and provides an easy method for local and systemic cytokine delivery. Alternatively, hybridoma cells can be encapsulated and the secreted antibody monitored in the serum. It was found that no host immune response was triggered by alginate encapsulated cells. The efficiency of treatment by encapsulated hybridoma cells was shown to be equivalent to that of injecting purified antibodies.

摘要

转染了白细胞介素-4、白细胞介素-5和干扰素-γ细胞因子基因的细胞系,使得功能性细胞因子能够以相对大的剂量在体内长时间递送,从而调节特定的免疫反应。通常,转染细胞对于实验动物来说是异种或同种异体的,必须以不会诱导宿主产生细胞反应的方式进行封装。海藻酸盐已被证明是一种在适合体内植入的温和条件下封装细胞的简单基质。体内植入后,封装细胞至少14天表达转染的白细胞介素-4基因,并通过调节正在进行的IgE反应在该期间显示出功能。贴壁生长的转染细胞的应用允许进行剂量反应滴定,并提供了一种局部和全身递送细胞因子的简便方法。或者,可以封装杂交瘤细胞并监测血清中分泌的抗体。发现海藻酸盐封装的细胞不会引发宿主免疫反应。结果表明,封装的杂交瘤细胞的治疗效果与注射纯化抗体的效果相当。

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