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胎骨组织共移植促进了人源化 NOD/SCID/IL-2Rγnull(NSG)小鼠中人类 B 细胞的发育和重建。

Co-transplantation of fetal bone tissue facilitates the development and reconstitution in human B cells in humanized NOD/SCID/IL-2Rγnull (NSG) mice.

机构信息

Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 440-746, Republic of Korea.

出版信息

J Clin Immunol. 2011 Aug;31(4):699-709. doi: 10.1007/s10875-011-9538-2. Epub 2011 May 5.

Abstract

BACKGROUND

In terms of the function and reconstitution efficacy of human immune cells, co-transplantation of human fetal tissues, such as thymus and liver, with CD34(+) hematopoietic stem cells (HSCs) has potential advantages in the generation of humanized mice.

OBJECTIVE AND METHODS

To examine the effects of bone tissues in the reconstitution of human immune cells, particularly in B cells, we generated a new humanized mice co-transplanted with human fetal thymus (hFT)/fetal bone (hFB) tissues and human fetal liver-derived CD34(+) cells.

RESULTS

Humanized mice exhibited effective reconstitution of human immune cells earlier compared to control humanized mice. In terms of quantity, the number of immune cells, such as human T, B, and monocyte/macrophages was significantly increased. Furthermore, significant increase of B cell progenitors and immature/naïve B cells could be detected in the bone marrow and spleen of humanized mice.

CONCLUSION

Our results demonstrate that co-transplantation of hFB tissue may facilitate the reconstitution of human B and T cells, and therefore the humanized model may be used to develop therapeutic human antibodies for clinical use.

摘要

背景

就人类免疫细胞的功能和重建功效而言,与 CD34(+)造血干细胞 (HSCs) 共移植人胎儿组织(如胸腺和肝脏)具有在生成人源化小鼠方面的潜在优势。

目的和方法

为了研究骨组织在人类免疫细胞,特别是 B 细胞重建中的作用,我们生成了一种新的人源化小鼠,其共移植了人胎胸腺(hFT)/胎骨(hFB)组织和人胎肝来源的 CD34(+)细胞。

结果

与对照人源化小鼠相比,人源化小鼠的人类免疫细胞重建更早且效果更有效。在数量方面,人 T、B 和单核细胞/巨噬细胞等免疫细胞的数量明显增加。此外,在人源化小鼠的骨髓和脾脏中可以检测到 B 细胞祖细胞和未成熟/幼稚 B 细胞的显著增加。

结论

我们的结果表明,hFB 组织的共移植可能有助于人类 B 和 T 细胞的重建,因此该人源化模型可用于开发用于临床应用的治疗性人抗体。

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