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成年小鼠中枢神经系统中通过骨髓移植实现小胶质细胞替代(Mr BMT)

Microglia replacement by bone marrow transplantation (Mr BMT) in the central nervous system of adult mice.

作者信息

Xu Zhen, Zhou Xin, Peng Bo, Rao Yanxia

机构信息

Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

Department of Neurosurgery, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China.

出版信息

STAR Protoc. 2021 Jul 7;2(3):100666. doi: 10.1016/j.xpro.2021.100666. eCollection 2021 Sep 17.

DOI:10.1016/j.xpro.2021.100666
PMID:34286294
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8273422/
Abstract

Microglia are important immune cells in the central nervous system (CNS). Mutations in microglia may cause CNS disorders. Replacement of dysfunctional microglia with allogeneic wild-type microglia can correct the gene deficiency, thus treating the neurogenic diseases. However, traditional approaches cannot efficiently replace microglia at the adulthood. Here, we introduce a potentially clinical-feasible strategy named microglia replacement by bone marrow transplantation that achieves efficient microglia replacement at the whole CNS scale, including the brain, spinal cord, and retina in adult mice. For complete details on the use and execution of this protocol, please refer to Xu et al. (2020). The original abbreviation of this microglia replacement strategy is mrBMT. We hereby change the name to Mr BMT.

摘要

小胶质细胞是中枢神经系统(CNS)中的重要免疫细胞。小胶质细胞的突变可能导致中枢神经系统疾病。用同种异体野生型小胶质细胞替代功能失调的小胶质细胞可以纠正基因缺陷,从而治疗神经源性疾病。然而,传统方法在成年期无法有效地替代小胶质细胞。在此,我们介绍一种具有潜在临床可行性的策略,即通过骨髓移植进行小胶质细胞替代,该策略可在成年小鼠的整个中枢神经系统范围内,包括脑、脊髓和视网膜,实现高效的小胶质细胞替代。有关本方案的使用和实施的完整详细信息,请参考Xu等人(2020年)的研究。这种小胶质细胞替代策略的原始缩写是mrBMT。我们在此将其名称更改为Mr BMT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/cc8ff68f501f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/155fc2b42843/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/6207eaae4456/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/29520afe3242/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/1861a65ca6fa/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/c971551ae67d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/2144cfe20b8f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/ca619ef274c0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/ea6b6739d54b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/cc8ff68f501f/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/155fc2b42843/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/6207eaae4456/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/29520afe3242/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/1861a65ca6fa/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/c971551ae67d/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/2144cfe20b8f/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/ca619ef274c0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/ea6b6739d54b/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f2a/8273422/cc8ff68f501f/gr8.jpg

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本文引用的文献

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Cell Rep. 2020 Aug 11;32(6):108041. doi: 10.1016/j.celrep.2020.108041.
2
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Cell Discov. 2018 Feb 27;4:9. doi: 10.1038/s41421-018-0011-8. eCollection 2018.
3
Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion.再殖的小胶质细胞完全来源于急性耗竭后残留小胶质细胞的增殖。
嵌合脑模型:揭示人类神经发育、衰老、疾病及细胞疗法的奥秘
Neuron. 2025 Jul 23;113(14):2230-2250. doi: 10.1016/j.neuron.2025.03.036. Epub 2025 Apr 28.
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Roles of blood monocytes carrying TREM2 mutation in pathogenesis of Alzheimer's disease and its therapeutic potential in APP/PS1 mice.携带TREM2突变的血液单核细胞在阿尔茨海默病发病机制中的作用及其对APP/PS1小鼠的治疗潜力。
Alzheimers Dement. 2025 Feb;21(2):e14402. doi: 10.1002/alz.14402. Epub 2024 Dec 30.
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Haploinsufficiency at the CX3CR1 locus of hematopoietic stem cells favors the appearance of microglia-like cells in the central nervous system of transplant recipients.造血干细胞 CX3CR1 基因座的单倍体不足有利于移植受者中枢神经系统中出现小胶质细胞样细胞。
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