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作 者:赵宁宁[1] 张正 王彦博[2] 师长宏[1] ZHAO Ningning;ZHANG Zheng;WANG Yanbo;SHI Changhong(Laboratory Animal Center, the Fourth Military Medical University, Xi’an, Shanxi 710032, China;the Fourth Brigade of Basic Medical College, the Fourth Military Medical University, Xi’an, Shanxi 710032, China)
机构地区:[1]第四军医大学实验动物中心,西安710032 [2]第四军医大学基础医学院四大队,西安710032
出 处:《中国实验动物学报》2018年第6期804-808,共5页Acta Laboratorium Animalis Scientia Sinica
基 金:国家自然科学基金项目(31772546;31572340)~~
摘 要:将患者的肿瘤组织移植于免疫缺陷小鼠体内建立的肿瘤移植模型(patient-derived xenograft, PDX)较好地保留了原发瘤的生物学特性,但瘤组织基质成分会在小鼠体内传代过程中逐渐被鼠源性基质代替,缺乏免疫系统的小鼠体内环境也会改变肿瘤的微环境,原发肿瘤的异质性会逐渐丢失,从而限制了该类模型的应用;将人的造血干细胞(hematopoietic stem cells, HSCs)移植于低剂量X线全身照射或其他方法清理骨髓的重度免疫缺陷小鼠,然后再将患者的瘤组织移植于该小鼠建立的人源化肿瘤模型(humanized patient-derived xenograft, Hu-PDX),具有与人相似的免疫系统,可以更好的保留原发瘤的异质性。研究证实人的HSCs在小鼠体内可以产生各种免疫细胞,使肿瘤生长微环境与人体更相似,更好的保留了肿瘤的异质性,为肿瘤的个体化研究提供了良好的动物模型。The patient-derived xenograft(PDX)model established by transplanting the patient’s tumor tissue into immunodeficient mice well preserves the biological characteristics of the primary tumor.However,the stroma component of the tumor tissue from patients is gradually replaced by the mouse-derived matrix over time in mice.The conditions in mice lacking an immune system will also change the microenvironment of the tumor,and the heterogeneity of the primary tumor will gradually be lost,thus limiting the application of the PDX model.The above problems can be resolved by a humanized patient-derived xenograft(Hu-PDX),which was established by transplanting human hematopoietic stem cells(HSCs)into immunodeficient mice,in which exposure to low-dose whole-body irradiation causes damage to bone marrow cells,or other method to clean up the bone marrow,forming humanized immune system mice(HISM).Then,the tumor tissues from patients can be transplanted into the HISM.HSCs in the mice can be induced to produce human immune cells.That makes the microenvironment of the tumor grown more similar to that in humans.This model well maintain the molecular heterogeneity of the primary tumor,and provides a good animal model for individualized tumor treatment.
关 键 词:患者来源肿瘤组织异种移植模型 肿瘤 免疫重建 人源化小鼠
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