Study on biodistribution of mixed activated killer immune cells in immunodeficient mice after administration
10.3760/cma.j.cn114015-20240809-00707
- VernacularTitle:混合活化杀伤免疫细胞给药后在免疫缺陷小鼠体内的生物分布研究
- Author:
Manman ZHAO
1
;
Lijun JIANG
;
Jing ZHAO
;
Hua JIANG
;
Ying HUANG
;
Hairuo WEN
;
Xiaobing ZHOU
Author Information
1. 中国食品药品检定研究院安全评价研究所，药物非临床安全评价研究北京市重点实验室，北京 100176
- Publication Type:Journal Article
- Keywords:
Animals, laboratory;
Mice;
Killer cells, natural;
Mixed activated killer immune cells;
Cell therapy products;
Tissue distribution
- From:
Adverse Drug Reactions Journal
2025;27(5):274-280
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the biodistribution characteristics of mixed activated killer (MAK) immune cells in immunodeficient mice after administration.Methods:Ninety-six immune immunodeficient (NOG) mice (half male and half female) were equally divided into MAK cell group and solvent control group. The MAK cell group mice were injected with DiR-labeled MAK cells via the tail vein, while those in the solvent control group were injected with an equal amount of solvent via the tail vein. The number of MAK cells in the peripheral blood of mice was detected using a flow cytometry at 11 time points from 15 minutes to 84 days after administration. The distribution of MAK cells in mice was measured using in vivo bioluminescence imaging at 18 time points from 5 minutes to 84 days after administration. And at 8 time points from 3 hours to 84 days after administration, the heart, liver, spleen, lungs, kidneys, brain, stomach, duodenum, colon, bone marrow, fat, skeletal muscle, testes/uterus, epididymis/ovary, and blood were collected from corresponding mice. The DNA levels of MAK cells in blood and various organs of these mice were detected using fluorescence real-time quantitative polymerase chain reaction (qPCR) method.Results:The flow cytometry results showed that MAK cells could be detected in the peripheral blood of mice 15 minutes after administration, and the highest number of MAK cells in blood appeared during 3 hours to 1 day. By 14 days after administration, MAK cells were almost undetectable in peripheral blood of mice. In vivo bioluminescence imaging results showed that the fluorescence intensity of MAK cells in mice was strongest on days 1 and 2 after administration, and MAK cells were mostly distributed in the liver, spleen, lung, and leg bone of mouse. The qPCR detection results showed that MAK cells were mainly distributed in the spleen and lungs. High levels of MAK cell DNA amplification were observed in organs such as the spleen and lungs 28-56 days after administration, and a certain amount of MAK cell DNA could still be detected in organs of mice such as the spleen at 84 days.Conclusions:After administration, MAK cells were mainly distributed in the spleen, lung, liver and other organs of NOG mice. From 28 to 56 days after administration, MAK cells are significantly activated and proliferate, and a certain amount of MAK cell DNA can still be detected in the spleen and other organs after 84 days in mice.
