Evidence map›Paper›PMID 40233761›Full record

ArticleCell stem cell2025

Harnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins.

Jean Paul Chadarevian, Hayk Davtyan, Alina L Chadarevian, Jasmine Nguyen, Joia K Capocchi, Lauren Le, Adrian Escobar, Talar Chadarevian, Kimiya Mansour, Ekaterina Deynega and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing 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

35 citing papers in PubMed.

  1. Review
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  5. Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026
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  19. Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Jean Paul ChadarevianDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Hayk DavtyanInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Alina L ChadarevianDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Jasmine NguyenInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.
Joia K CapocchiInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.
Lauren LeInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.
Adrian EscobarSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Talar ChadarevianSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Kimiya MansourSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Ekaterina DeynegaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.
Michael MgerianSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Christina TuInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Sepideh Kiani ShabestariDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
William Carlen-JonesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.
Ghazaleh Eskandari-SedighiInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA.
Jonathan HasselmannInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA.
Robert C SpitaleDepartment of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: rspitale@uci.edu.
Mathew Blurton-JonesDepartment of Neurobiology & Behavior, University of California, Irvine, Irvine, CA 92697, USA; Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA 92697, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: mblurton@uci.edu.

Funding

The Alzheimer's Disease Research Center at the University of California, IrvineP30AG066519 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Mathew Mark Blurton-Jones · 2020 to 2026
$27.9M
Training in the Neurobiology of Aging and Alzheimers DiseaseT32AG000096 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI VIVEK SWARUP, Craig E Stark · 1985 to 2026
$9.6M
Using human iPSC derived microglia and chimeric models to examine the role of PLCG2 in Alzheimers diseaseR01AG061895 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAVTYAN, HAYK · 2018 to 2022
$2.9M
Examining the role of adaptive immunity in Alzheimer's Disease pathogenesisRF1AG055524 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2017 to 2017
$2.7M
Training in Translational ADRD Neuroscience (TITAN)T32AG073088 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Joshua Grill, Elizabeth Head · 2021 to 2026
$2.2M
A novel platform for the investigation of human microgliaRF1DA048813 · NIDA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK, GANDHI, SUNIL · 2019 to 2021
$2.1M
Manipulating DNA repair enzymes to examine the interactions between aging and Alzheimers disease with iPSC-derived microgliaR01AG056303 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2017 to 2021
$1.9M
The role of TREM2 in human microglial function and Alzheimer disease pathogenesisRF1AG048099 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2014 to 2014
$1.9M
ENGINEERED HUMAN MICROGLIA AS A CELL-BASED THERAPY FOR A-BETA PLAQUE REMOVALR21AG073787 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2021 to 2022
$424k
Assessing cell specific proteomes in the presence and absence of C5a complement signaling in Alzheimer's disease modelsR21AG068573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI TENNER, ANDREA JOAN · 2020 to 2021
$417k
NIA NIH HHS P30 AG066519NIA NIH HHS R01 AG056303NIA NIH HHS R01 AG061895NIA NIH HHS R21 AG068573NIA NIH HHS R21 AG073787NIA NIH HHS RF1 AG048099NIA NIH HHS RF1 AG055524NIA NIH HHS T32 AG000096NIA NIH HHS T32 AG073088NIDA NIH HHS RF1 DA048813
6 · The paper itself

Abstract

Widespread delivery of therapeutic proteins to the brain remains challenging. To determine whether human induced pluripotent stem cell (iPSC)-microglia (iMG) could enable brain-wide and pathology-responsive delivery of therapeutic cargo, we utilized CRISPR gene editing to engineer iMG to express the Aβ-degrading enzyme neprilysin under control of the plaque-responsive promoter, CD9. To further determine whether increased engraftment enhances efficacy, we utilized a CSF1R-inhibitor resistance approach. Interestingly, both localized and brain-wide engraftment in Alzheimer's disease (AD) mice reduced multiple biochemical measures of pathology. However, within the plaque-dense subiculum, reductions in plaque load, dystrophic neurites, and astrogliosis and preservation of neuronal density were only achieved following widespread microglial engraftment. Lastly, we examined chimeric models of breast cancer brain metastases and demyelination, demonstrating that iMG adopt diverse transcriptional responses to differing neuropathologies, which could be harnessed to enable widespread and pathology-responsive delivery of therapeutics to the CNS.

Indexed as

Central Nervous SystemInduced Pluripotent Stem CellsMicrogliaAlzheimer DiseaseAnimalsBrainFemaleHumansMiceNeprilysinNeprilysinAlzheimer’s diseaseCRISPRiMGimmune cell therapyiPSCmicrogliamicroglia replacementneprilysinneurodegenerationpayload delivery

Identifiers

PMID40233761
PMCPMC12360426

What OpenQuestion holds

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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.