Murine iPSC-derived microglia and macrophage cell culture models recapitulate distinct phenotypical and functional properties of classical and alternative neuro-immune polarisation

Quarta, Alessandra; Blon, Debbie Le; D'aes, Tine; Pieters, Zoë; Taj, Somayyeh Hamzei; Miró-Mur, Francesc; Luyckx, Evi; Breedam, Elise Van; Daans, Jasmijn; Goossens, Herman; Dewilde, Sylvia; Hens, Niel; Pasque, Vincent; Planas, Anna M.; Hoehn, Mathias; Berneman, Zwi N.; Ponsaerts, Peter

doi:10.1016/j.bbi.2019.09.009

Cited by 20 publications

(47 citation statements)

References 82 publications

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“…Murine iPSC-microglia were generated from CX 3 CR1 eGFP/+ CCR2 RFP/+ iPSCs according to our previously optimized method (Quarta et al, 2019). Briefly, CX 3 CR1 eGFP/+ CCR2 RFP/+ iPSCs were seeded on agarose-coated dishes to promote cell aggregation and differentiation into embryoid bodies (EBs).…”

Section: Differentiation Of Ipsc-microgliamentioning

confidence: 99%

“…Starting from newly established murine CX 3 CR1 eGFP/+ CCR2 RFP/+ iPSCs, we previously reported the efficient generation of ramified CX 3 CR1 + (eGFP + ) iPSC-microglia in co-culture with astrocytecommitted embryonic brain-derived NSC (NSC) (Figure 2a), as well as round-shaped Iba1 + CX 3 CR1 − (eGFP − ) iPSC-macrophages in monoculture ( Figure 2b) (Quarta et al, 2019). To further characterize the identity of these in vitro differentiated murine iPSC-microglia and iPSC-macrophages, we here performed whole-transcriptome analysis using next-generation RNA-Seq.…”

Section: Murine Ipsc-microglia and Ipscmacrophages Display Distinctmentioning

confidence: 99%

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Murine induced pluripotent stem cell‐derived neuroimmune cell culture models emphasize opposite immune‐effector functions of interleukin 13‐primed microglia and macrophages in terms of neuroimmune toxicity

Quarta

Meese

Pieters

et al. 2020

Glia

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Cellular models of induced pluripotent stem cell (iPSC)-derived microglia and macrophages are an emerging toolbox to investigate neuroinflammation in vitro. We previously demonstrated that murine iPSC-microglia and iPSC-macrophages display phenotypical activation properties highly comparable to microglia and macrophages in vivo. Here we extended the characterization of iPSC-microglia and iPSCmacrophages with the analysis of their transcriptome profile. Next, these cellular models were employed to evaluate neuroimmune toxicity in vitro and to investigate the immune-modulatory properties of interleukin 13 (IL13), a cytokine known for its ability to protect against neuroinflammation-induced pathology by modulating microglia and macrophage activation. iPSC-microglia and iPSC-macrophages, in coculture with astrocyte-committed neural stem cells (NSC), were (pre)treated with IL13 and stimulated with lipopolysaccharide (LPS) and interferon γ (IFNγ), to assess how IL13 modulates their inflammatory response. Additionally, the use of luciferaseexpressing NSC (Luc-NSC) allowed real-time monitoring of immune-mediated neurotoxicity. Despite the known anti-inflammatory properties of IL13, iPSC-microglia primed with IL13 before LPS + IFNγ stimulation significantly increased NO secretion. This was associated with a marked reduction of the luminescence signal produced by Luc-NSC. Interestingly, we observed that IL13 signaling has a divergent functional outcome in microglia as compared to macrophages, as for the latter no major alterations in NO release and Luc-NSC viability were observed upon IL13 (pre)treatment. Finally, the striking IL13-induced upregulation of NO secretion by microglia under pro-inflammatory conditions was confirmed in vivo, where intracerebral delivery of IL13 increased inducible nitric oxide synthase mRNA expression. Concluding, we applied iPSC-derived neuroimmune cell culture models to identify distinct neuroimmune (toxicity) responses of microglia and macrophages to IL13-based immune modulation.

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Section: Differentiation Of Ipsc-microgliamentioning

confidence: 99%

Section: Murine Ipsc-microglia and Ipscmacrophages Display Distinctmentioning

confidence: 99%

Murine induced pluripotent stem cell‐derived neuroimmune cell culture models emphasize opposite immune‐effector functions of interleukin 13‐primed microglia and macrophages in terms of neuroimmune toxicity

Quarta

Meese

Pieters

et al. 2020

Glia

Self Cite

View full text Add to dashboard Cite

show abstract

“…Three murine cell culture models, namely iPSC microglia, iPSC-macrophages and NSC-primed iPSC-macrophages were cultured to elucidate pro-inflammatory and anti-inflammatory features of brain resident and infiltrating monocytes during cerebral ischemia. Consistency of results in vitro and in vivo suggested that iPSC-derived neuro-immune cell culture models can be possibly useful in related researches (96).…”

Section: Resident Glial Cells and Infiltrating Macrophages/monocytesmentioning

confidence: 99%

Immunoreactive Cells After Cerebral Ischemia

et al. 2019

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The immune system is rapidly activated after ischemic stroke. As immune cells migrate and infiltrate across the blood-brain barrier into the ischemic region, a cascade of cellular and molecular biological reactions occur, involving migrated immune cells, resident glial cells, and the vascular endothelium. These events regulate infarction evolution and thus influence the outcome of ischemic stroke. Most immune cells exert dual effects on cerebral ischemia, and some crucial cells may become central targets in ischemic stroke treatment and rehabilitation.

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“…It was resistant to stress and maintained the balance of cellular metabolism when sensing and decomposing mitochondrial ROS. ( Hardie et al., 2012 ; Quarta et al., 2019 ), which were risk factors for pathologic fibrotic processes ( Salminen and Kaarniranta, 2012 ). Not only that effects of oral administration of metformin on ocular disease have also attracted widespread attention, the preclinical studies showed that metformin exerted protective effects on reducing risks of developing open angle glaucoma (OAG) ( Lin et al., 2015 ) and had obvious anti-inflammatory and anti-angiogenic effects on retinal vascular hyperplasia ( Han et al., 2018b ).…”

Section: Introductionmentioning

confidence: 99%

Eye Drops of Metformin Prevents Fibrosis After Glaucoma Filtration Surgery in Rats via Activating AMPK/Nrf2 Signaling Pathway

Jiang

et al. 2020

Front. Pharmacol.

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Metformin has effective therapeutic effects in anti-tumor and anti-fibrotic diseases. However, how the antifibrotic effect of metformin in the eye and how it is transferred are still unclear. Here, the eye drop of metformin treatment was studied in Sprague-Dawley (SD) rats of glaucoma filtrating surgery (GFS). Rats were administered randomly bilateral drops: control group (without surgery), GFS group, metformin group or mitomycin C (MMC) group (sponge application intraoperatively, 0.02%). Bleb features and intraocular pressure (IOP) were assessed for postoperative week 4. Metformin effectively inhibited fibrosis and improved the surgical outcomes of GFS. In vitro, we found that the degree of oxidative stress and fibrosis in metformin pretreated-Human Conjunctival Fibroblasts (HConFs) were reduced; the pro-fibrotic response of HConFs were decreased by inducing macrophagic polarity changes. Besides, the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2)/ AMP-activated protein kinase (AMPK) and the competition of organic cation transporters (OCTs) effectively reduced the anti-fibrotic capability of metformin. Together, this experiment indicates that metformin enters into HConFs cell with OCTs, which can protect against filtrating blebs scar formation in SD rats of GFS via activating AMPK/Nrf2 axis and the downregulation of profibrogenic and inflammatory biomarkers.

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Murine iPSC-derived microglia and macrophage cell culture models recapitulate distinct phenotypical and functional properties of classical and alternative neuro-immune polarisation

Cited by 20 publications

References 82 publications

Murine induced pluripotent stem cell‐derived neuroimmune cell culture models emphasize opposite immune‐effector functions of interleukin 13‐primed microglia and macrophages in terms of neuroimmune toxicity

Murine induced pluripotent stem cell‐derived neuroimmune cell culture models emphasize opposite immune‐effector functions of interleukin 13‐primed microglia and macrophages in terms of neuroimmune toxicity

Immunoreactive Cells After Cerebral Ischemia

Eye Drops of Metformin Prevents Fibrosis After Glaucoma Filtration Surgery in Rats via Activating AMPK/Nrf2 Signaling Pathway

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