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人源化小鼠用于研究持续的恶性疟原虫血液阶段感染和传播

更新时间:2025-07-02   点击次数:457次

中文摘要:

恶性疟原虫是人类广泛的疟疾寄生虫。由于存在血管外的储存库以及从休眠肝脏阶段复发的感染,恶性疟原虫特别难以控制和消除。实验研究受到限制,因为无法体外维持恶性疟原虫的培养,这是由于它对未成熟红细胞的趋向。在这里,我们描述了一种新的类人小鼠模型,它能够支持有效的人类红细胞生成并维持接种的冷冻保存恶性疟原虫的持久增殖及其性别分化,包括在骨髓中。成熟性配子被传递到按蚊中,从而形成唾液腺孢子虫。重要的是,在二次转移新鲜或冷冻感染的骨髓细胞到未感染的嵌合体后,血液阶段的恶性疟原虫得以维持。该模型提供了一个的工具,以体内方式研究红细胞内恶性疟原虫的生物学。


英文摘要:

Plasmodium vivax is the most widespread human malaria parasite. Due to the presence of extravascular reservoirs and relapsing infections from dormant liver stages, P. vivax is particularly difficult to control and eliminate. Experimental research is hampered by the inability to maintain P. vivax cultures in vitro, due to its tropism for immature red blood cells (RBCs). Here, we describe a new humanized mice model that can support efficient human erythropoiesis and maintain long-lasting multiplication of inoculated cryopreserved P. vivax parasites and their sexual differentiation, including in bone marrow. Mature gametocytes were transmitted to Anopheles mosquitoes, which led to the formation of salivary gland sporozoites. Importantly, blood-stage P. vivax parasites were maintained after the secondary transfer of fresh or frozen infected bone marrow cells to naïve chimeras. This model provides a unique tool for investigating, in vivo, the biology of intraerythrocytic P. vivax.


论文信息:

论文题目:Humanized mice for investigating sustained Plasmodium vivax blood-stage infections and transmission

期刊名称:Nature Communications

时间期卷:13, Article number: 4123 (2022)

在线时间:2022年7月15日

DOI:doi.org/10.1038/s41467-022-31864-6

  

产品信息:

货号:CP-005-005

规格:5ml+5ml

品牌:Liposoma

产地:荷兰

名称:Clodronate Liposomes and Control Liposomes

办事处:Target Technology(靶点科技)


氯膦酸盐脂质体清除单核巨噬细胞,在人源化小鼠模型疟原虫诱导的炎性模型中单核巨噬细胞功能研究,荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications:人源化小鼠用于研究持续的恶性疟原虫血液阶段感染和传播。

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Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法:

HIS-HEry mouse infection with P. vivax

P. vivax isolates were thawed with a stepwise NaCl method, as previously described33, and washed in PBS. Before being used to infect mice, the isolates were tested for Plasmodium parasitemia by examining thick PB smears with Giemsa staining. Next, RBC pellets of the isolates were resuspended in PBS at a concentration of 2.5.106 to 5.106 parasitized RBCs per ml. One day before infection, 12- to 20-week-old HIS-HEry chimeras received intravenous injections of 200 μl liposome clodronate (Liposoma BV, The Netherlands). This injection was repeated every 5 days for the duration of the experiments. HIS-HEry mice were infected intravenously, under anesthesia, with 106−5.106 infected RBCs from either a single isolate (Pv1, Pv2, Pv3, or Pv4) or a mixture of three isolates (Pv5), except when stated otherwise in figure legends. Then, BM and blood were collected from euthanized mice on days 1, 7, 14, or 21 after infection. To collect BM, the two femurs, tibias, and humeri were dissected, the bones were crushed, and cell suspensions were filtered through 40-μM filters before processing. Each experiment was conducted with chimeras engrafted with CD34+ cells from the same CB donor.

  

材料和方法文献截图:

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