Development of LT-HSC-Reconstituted Non-Irradiated NBSGW Mice for the Study of Human Hematopoiesis In Vivo.
Development of LT-HSC-Reconstituted Non-Irradiated NBSGW Mice for the Study of Human Hematopoiesis In Vivo.
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DOI：
10.3389/fimmu.2021.642198
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发表时间：
2021
影响因子：
7.3
通讯作者：
Issa F
中科院分区：
文献类型：
--
作者：
Adigbli G;Hua P;Uchiyama M;Roberts I;Hester J;Watt SM;Issa F
人源化免疫系统(HIS)小鼠模型是体内研究人类造血的有用工具。然而，他目前使用的大多数模型偏向于淋巴细胞发育，无法支持长期的多系白细胞和红细胞。那些成功的多血统重建通常需要昂贵的预适应步骤，导致动物发病，技术要求高，重复性差。在这项研究中，我们使用HSPC-NBSGW小鼠来应对这一挑战，在NOD，B6，SCID IL-2Rγ-/-KitW41/W41(NBSGW)小鼠中，植入人CD133+造血干/祖细胞(HSPC)，而不需要通过亚致死性辐射进行预适应。这些HSPC富含长期造血干细胞(LT-HSCs)，而NBSGW小鼠允许植入人类造血干细胞(HSC)，从而减少了成功发育HIS所需的细胞数量。B细胞的重建效率最高，包括能够在同种异体刺激后进行类别转换的成熟B细胞，以及在淋巴器官和外周血液中处于不同成熟阶段的T细胞。在胸腺中，人类胸腺细胞在发育的所有主要阶段都被识别出来。表型不同的髓系细胞亚群，包括树突状细胞和成熟单核细胞，在骨髓和脾中不同程度地植入，并在外周血中循环。最后，我们观察到巨噬细胞清除后维持在外周高水平的人红细胞。因此，HSPC-NBSGW模型为研究人类血液学、免疫学过程和病理学提供了一个有用的平台。
Humanized immune system (HIS) mouse models are useful tools for the in vivo investigation of human hematopoiesis. However, the majority of HIS models currently in use are biased towards lymphocyte development and fail to support long-term multilineage leucocytes and erythrocytes. Those that achieve successful multilineage reconstitution often require preconditioning steps which are expensive, cause animal morbidity, are technically demanding, and poorly reproducible. In this study, we address this challenge by using HSPC-NBSGW mice, in which NOD,B6.SCID IL-2rγ -/-KitW41/W41 (NBSGW) mice are engrafted with human CD133+ hematopoietic stem and progenitor cells (HSPCs) without the need for preconditioning by sublethal irradiation. These HSPCs are enriched in long-term hematopoietic stem cells (LT-HSCs), while NBSGW mice are permissive to human hematopoietic stem cell (HSC) engraftment, thus reducing the cell number required for successful HIS development. B cells reconstitute with the greatest efficiency, including mature B cells capable of class-switching following allogeneic stimulation and, within lymphoid organs and peripheral blood, T cells at a spectrum of stages of maturation. In the thymus, human thymocytes are identified at all major stages of development. Phenotypically distinct subsets of myeloid cells, including dendritic cells and mature monocytes, engraft to a variable degree in the bone marrow and spleen, and circulate in peripheral blood. Finally, we observe human erythrocytes which persist in the periphery at high levels following macrophage clearance. The HSPC-NBSGW model therefore provides a useful platform for the study of human hematological and immunological processes and pathologies.
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影响因子：
20.3
作者：
Hua P;Hester J;Adigbli G;Li R;Psaila B;Roy A;Bataille CJR;Wynne GM;Jackson T;Milne TA;Russell AJ;Davies J;Roberts I;Issa F;Watt SM
通讯作者：
Watt SM
脾脏中的B细胞发育发生在离散的步骤中，并取决于B细胞受体衍生的信号的质量。
影响因子：
15.3
作者：
Loder, F;Mutschler, B;Ray, R J;Paige, C J;Sideras, P;Torres, R;Lamers, M C;Carsetti, R
通讯作者：
Carsetti, R
DOI：
10.1084/jem.20151039
发表时间：
2016-01-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lang J;Ota T;Kelly M;Strauch P;Freed BM;Torres RM;Nemazee D;Pelanda R
通讯作者：
Pelanda R
影响因子：
3.2
作者：
Jangalwe, Sonal;Shultz, Leonard D;Mathew, Anuja;Brehm, Michael A
通讯作者：
Brehm, Michael A
影响因子：
5.4
作者：
Agematsu, K;Nagumo, H;Komiyama, A
通讯作者：
Komiyama, A