Evidence map›Paper›PMID 39514271›Full record

ArticleeLife2024

Human-induced pluripotent stem cell-derived microglia integrate into mouse retina and recapitulate features of endogenous microglia.

Wenxin Ma, Lian Zhao, Biying Xu, Robert N Fariss, T Michael Redmond, Jizhong Zou, Wai T Wong, Wei Li

Abstract read
In one paragraph

Article in eLife, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Wenxin MaRetinal Neurophysiology Section, National Eye Institute, Bethesda, United States.ORCID https://orcid.org/0000-0001-8396-6625
Lian ZhaoGenetic Engineering Core, National Eye Institute, Bethesda, United States.
Biying XuImmunoregulation Section, National Eye Institute, Bethesda, United States.ORCID https://orcid.org/0000-0001-8608-6797
Robert N FarissBiological Imaging Core, National Eye Institute, Bethesda, United States.
T Michael RedmondMolecular Mechanisms Section, National Eye Institute, Bethesda, United States.
Jizhong ZouiPSC Core, National Heart, Lung, and Blood Institute, Bethesda, United States.
Wai T WongTiresias Bio, Half Moon Bay, United States.ORCID https://orcid.org/0000-0003-0681-4016
Wei LiRetinal Neurophysiology Section, National Eye Institute, Bethesda, United States.ORCID https://orcid.org/0000-0002-2897-649X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Microglia exhibit both maladaptive and adaptive roles in the pathogenesis of neurodegenerative diseases and have emerged as a cellular target for central nervous system (CNS) disorders, including those affecting the retina. Replacing maladaptive microglia, such as those impacted by aging or over-activation, with exogenous microglia that can enable adaptive functions has been proposed as a potential therapeutic strategy for neurodegenerative diseases. To investigate microglia replacement as an approach for retinal diseases, we first employed a protocol to efficiently generate human-induced pluripotent stem cell (hiPSC)-derived microglia in quantities sufficient for in vivo transplantation. These cells demonstrated expression of microglia-enriched genes and showed typical microglial functions such as LPS-induced responses and phagocytosis. We then performed xenotransplantation of these hiPSC-derived microglia into the subretinal space of adult mice whose endogenous retinal microglia have been pharmacologically depleted. Long-term analysis post-transplantation demonstrated that transplanted hiPSC-derived microglia successfully integrated into the neuroretina as ramified cells, occupying positions previously filled by the endogenous microglia and expressed microglia homeostatic markers such as P2ry12 and Tmem119. Furthermore, these cells were found juxtaposed alongside residual endogenous murine microglia for up to 8 months in the retina, indicating their ability to establish a stable homeostatic state in vivo. Following retinal pigment epithelial cell injury, transplanted microglia demonstrated responses typical of endogenous microglia, including migration, proliferation, and phagocytosis. Our findings indicate the feasibility of microglial transplantation and integration in the retina and suggest that modulating microglia through replacement may be a therapeutic strategy for treating neurodegenerative retinal diseases.

Indexed as

Induced Pluripotent Stem CellsMicrogliaRetinaAnimalsCell DifferentiationHumansMicePhagocytosishuman iPSCmicrogliamouseNaIO3PLX-5622regenerative medicineretinal transplantationRPEstem cells

Identifiers

PMID39514271
PMCPMC11587526

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.