Efficient Strategies for Microglia Replacement in the Central Nervous System

Xu, Zhen; Rao, Yu; Huang, Yubin; Zhou, Tian; Feng, Rui; Xiong, Sidong; Yuan, Ti‐Fei; Qin, Shan; Lu, Yijie; Zhou, Xin; Li, Xiaoyü; Qin, Bo; Mao, Ying; Peng, Bo

doi:10.1016/j.celrep.2020.108041

Cited by 101 publications

(116 citation statements)

References 82 publications

(117 reference statements)

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“…One significant limitation of the traditional transplantation method is the low replacement efficiency, which may be another reason for inconsistent therapeutic outcomes of microglia transplantation or alloreplacement. In 2020, Xu et al reported three highly efficient strategies for microglia replacement globally in the CNS or in specific brain regions 141 . Compared to traditional methods, they created niches in the mouse brain that were microglia‐free, prior to non‐self cell transplantation.…”

Section: Therapeutic Opportunities and Challenges In Targeting Microgmentioning

confidence: 99%

“…These microglia‐free niches aided survival and engraftment of transplanted cells. The transplantation strategies also open up a window for treatment of microglia‐associated CNS disorders, aside from stroke 141 . Although microglia alloreplacement showed therapeutic promise, more studies are needed to understand the exact role, mechanism, and integration of grafted microglia and their impact on outcomes after stroke.…”

Section: Therapeutic Opportunities and Challenges In Targeting Microgmentioning

confidence: 99%

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Microglial/Macrophage polarization and function in brain injury and repair after stroke

et al. 2021

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Stroke is a leading cause of disability and mortality, with limited treatment options. After stroke injury, microglia and CNS‐resident macrophages are rapidly activated and regulate neuropathological processes to steer the course of functional recovery. To accelerate this recovery, microglia can engulf dying cells and clear irreparably‐damaged tissues, thereby creating a microenvironment that is more suitable for the formation of new neural circuitry. In addition, monocyte‐derived macrophages cross the compromised blood‐brain barrier to infiltrate the injured brain. The specific functions of myeloid lineage cells in brain injury and repair are diverse and dependent on phenotypic polarization statuses. However, it remains to be determined to what degree the CNS‐invading macrophages occupy different functional niches from CNS‐resident microglia. In this review, we describe the physiological characteristics and functions of microglia in the developing and adult brain. We also review (a) the activation and phenotypic polarization of microglia and macrophages after stroke, (b) molecular mechanisms that control polarization status, and (c) the contribution of microglia to brain pathology versus repair. Finally, we summarize current breakthroughs in therapeutic strategies that calibrate microglia/macrophage responses after stroke.

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Section: Therapeutic Opportunities and Challenges In Targeting Microgmentioning

confidence: 99%

Section: Therapeutic Opportunities and Challenges In Targeting Microgmentioning

confidence: 99%

Microglial/Macrophage polarization and function in brain injury and repair after stroke

et al. 2021

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“…An alternative approach, of transplantation of genetically-engineered autologous hematopoietic stem cells, has proven to be beneficial in X-linked adrenoleukodystrophy [115,116]. Recently strategies for efficient microglial replacement therapy have been developed in mouse [117][118][119].…”

Section: Emerging Therapies For Crlmentioning

confidence: 99%

Modeling CSF‐1 receptor deficiency diseases – how close are we?

2021

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The role of colony stimulating factor-1 receptor (CSF-1R) in macrophage and organismal development has been extensively studied in mouse. Within the last decade mutations in the CSF1R have been shown to cause rare diseases of both pediatric (Brain Abnormalities, Neurodegeneration, and Dysosteosclerosis (BANDDOS), OMIM #618476) and adult [CSF1R-related leukoencephalopathy (CRL), OMIM #221820] onset. Here we review the genetics, penetrance and histopathological features of these diseases and discuss to what extent the animal models of Csf1r deficiency currently available provide systems in which to study the underlying mechanisms involved.

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“…The first step of Mr MT is replacing the endogenous microglia with tamoxifen-sensitive CX3CR1-CreER::DTA microglia-like cells through Mr BMT ( Xu et al., 2020 ). For the detailed protocol of Mr BMT, please kindly refer to Xu et al.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%

“…We hereby change the name to Mr MT. For complete details on the use and execution of this protocol, please refer to Xu et al. (2020) .…”

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confidence: 99%

Microglia replacement by microglia transplantation (Mr MT) in the adult mouse brain

Peng

Rao

2021

STAR Protocols

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Summary Mutations in microglia may cause brain disorders. Replacement of dysfunctional microglia by allogeneic wild-type microglia from bone marrow transplantation (Mr BMT) or peripheral blood can correct the gene deficiency at the brain-wide scale but cannot achieve precise replacement at specific brain regions. Here, we introduce a strategy with potential clinical relevance—microglia replacement by microglia transplantation (Mr MT), combining tamoxifen-induced ablation of Mr BMT cells and intracranial injection of microglia to mouse brain, to achieve region-sepcific microglia replacement. The original abbreviation of this microglia replacement strategy is mrMT. We hereby change the name to Mr MT. For complete details on the use and execution of this protocol, please refer to Xu et al. (2020) .

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Efficient Strategies for Microglia Replacement in the Central Nervous System

Cited by 101 publications

References 82 publications

Microglial/Macrophage polarization and function in brain injury and repair after stroke

Microglial/Macrophage polarization and function in brain injury and repair after stroke

Modeling CSF‐1 receptor deficiency diseases – how close are we?

Microglia replacement by microglia transplantation (Mr MT) in the adult mouse brain

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