一种用于研究骨髓中传播阶段归巢和隔离的人源化模型。
An humanized model to study homing and sequestration of transmission stages in the bone marrow.
机构信息
Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Dipartimento Malattie Infettive, Istituto Superiore di Sanità, Rome, Italy.
出版信息
Front Cell Infect Microbiol. 2023 Apr 19;13:1161669. doi: 10.3389/fcimb.2023.1161669. eCollection 2023.
INTRODUCTION
Recent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of malaria by providing a "niche" for the maturation of the parasite gametocytes, responsible for human-to-mosquito transmission. Suitable humanized models to study the mechanisms of the interplay between the parasite and the human BM components are still missing.
METHODS
We report a novel experimental system based on the infusion of immature gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells.
RESULTS
We demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types.
DISCUSSION
Our model represents a powerful tool to study BM function and the interplay essential for parasite transmission in malaria and can be extended to study other infections in which the human BM plays a role.
简介
最近的证据表明，骨髓（BM）在疟疾的传播中起着关键作用，为寄生虫配子体的成熟提供了一个“小生境”，负责人类到蚊子的传播。仍然缺乏适合研究寄生虫与人类 BM 成分相互作用机制的人类化模型。
方法
我们报告了一种新的实验系统，该系统基于将未成熟配子体输注到携带嵌合异位骨赘的免疫功能低下的小鼠中，这些骨赘的基质和骨部分来自人类成骨前体细胞。
结果
我们证明未成熟的配子体在几分钟内归巢到骨赘，并到达血管外区域，在那里它们与不同的人类 BM 基质细胞保持接触。
讨论
我们的模型代表了一种强大的工具，可以研究 BM 功能和寄生虫传播所必需的相互作用，也可以扩展到研究其他人类 BM 发挥作用的感染。
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