Expression and significance of SDF-1 and its receptor CXCR4 in the retina of pregnant rats after optic nerve injury

Liu, Tiegang; Tang, Xin; Yao, Ling; Song, Hui

doi:10.1177/2058739218819675

Cited by 3 publications

(1 citation statement)

References 13 publications

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“…Despite our CXCR4 blocking experiment demonstrating the direct effect of SDF1 on donor RGC translocation into the GCL, host neurons within the retina also express CXCR4, 88 and could be adversely affected by SDF1. To investigate the effects of SDF1 on retinal lamination and position of host retinal neurons, we delivered a range of concentrations (0, 1, 10, and 200 ng SDF) into the mouse vitreous and collected retinas for histology 24 hours after the injection.…”

Section: Sdf1 Treatment Causes the Displacement Of Endogenously Regen...mentioning

confidence: 58%

Introduced chemokine gradients guide transplanted and regenerated retinal neurons toward their natural position in the retina

Soucy

Todd

Kryukov

et al. 2022

Preprint

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Ongoing cell replacement studies and clinical trials have demonstrated the need to control donor and newborn cell behavior within their target tissue. Here we present a methodology to guide stem cell-derived and endogenously regenerated neurons by engineering the microenvironment. Being an ″approachable part of the brain,″ the eye provides a unique opportunity to study donor neuron fate, migration, and integration within the central nervous system. Glaucoma and other optic neuropathies lead to the permanent loss of retinal ganglion cells (RGCs) - the neurons in the retina that transfer all visual information from the eye to the brain. Cell transplantation and transdifferentiation strategies have been proposed to restore RGCs, and one of the significant barriers to successful RGC integration into the existing retinal circuitry is cell migration towards their natural position in the retina. Here we describe a framework for identifying, selecting, and applying chemokines to direct cell migration in vivo within the retina. We have performed an in silico analysis of the single-cell transcriptome of the developing human retina and identified six receptor-ligand candidates to guide stem cell-derived or newborn neurons. The lead candidates were then tested in functional in vitro assays for their ability to guide stem cell-derived RGCs. For the in vivo studies, donor and newborn neurons were differentiated in human and mouse retinal organoids or endogenously reprogrammed with proneuronal transcription factors, respectively. An exogenous stromal cell-derived factor-1 (SDF1) gradient led to a 2.7-fold increase in donor RGC migration into the ganglion cell layer and a 3.3-fold increase in the displacement of newborn RGCs out of the inner nuclear layer. Furthermore, by altering the migratory profile of donor RGCs toward multipolar migration, overall migration was improved in mature retinal tissues. Together, these results highlight the ability and importance of engineering the tissue microenvironment and the individual cells for research and clinical applications in gene and cell therapies.

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Section: Sdf1 Treatment Causes the Displacement Of Endogenously Regen...mentioning

confidence: 58%

Introduced chemokine gradients guide transplanted and regenerated retinal neurons toward their natural position in the retina

Soucy

Todd

Kryukov

et al. 2022

Preprint

View full text Add to dashboard Cite

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Lymphocytic microparticles suppress retinal angiogenesis via targeting Müller cells in the ischemic retinopathy mouse model

Cai

Tahiri

Fortin

et al. 2021

Experimental Cell Research

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Controlling donor and newborn neuron migration and maturation in the eye through microenvironment engineering

Soucy,

Todd,

Kriukov

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Ongoing cell therapy trials have demonstrated the need for precision control of donor cell behavior within the recipient tissue. We present a methodology to guide stem cell–derived and endogenously regenerated neurons by engineering the microenvironment. Being an “approachable part of the brain,” the eye provides a unique opportunity to study neuron fate and function within the central nervous system. Here, we focused on retinal ganglion cells (RGCs)—the neurons in the retina are irreversibly lost in glaucoma and other optic neuropathies but can potentially be replaced through transplantation or reprogramming. One of the significant barriers to successful RGC integration into the existing mature retinal circuitry is cell migration toward their natural position in the retina. Our in silico analysis of the single-cell transcriptome of the developing human retina identified six receptor-ligand candidates, which were tested in functional in vitro assays for their ability to guide human stem cell–derived RGCs. We used our lead molecule, SDF1, to engineer an artificial gradient in the retina, which led to a 2.7-fold increase in donor RGC migration into the ganglion cell layer (GCL) and a 3.3-fold increase in the displacement of newborn RGCs out of the inner nuclear layer. Only donor RGCs that migrated into the GCL were found to express mature RGC markers, indicating the importance of proper structure integration. Together, these results describe an “in silico–in vitro–in vivo” framework for identifying, selecting, and applying soluble ligands to control donor cell function after transplantation.

show abstract

Expression and significance of SDF-1 and its receptor CXCR4 in the retina of pregnant rats after optic nerve injury

Cited by 3 publications

References 13 publications

Introduced chemokine gradients guide transplanted and regenerated retinal neurons toward their natural position in the retina

Introduced chemokine gradients guide transplanted and regenerated retinal neurons toward their natural position in the retina

Lymphocytic microparticles suppress retinal angiogenesis via targeting Müller cells in the ischemic retinopathy mouse model

Controlling donor and newborn neuron migration and maturation in the eye through microenvironment engineering

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