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Rare intercellular material transfer as a confound to interpreting inner retinal neuronal transplantation following internal limiting membrane disruption

Zhang, Kevin Y; Nagalingam, Arumugam; Mary, Stella; Aguzzi, Erika A; Li, Weifeng; Chetla, Nitin; Smith, Barbara; ... Johnson, Thomas V; + view all (2023) Rare intercellular material transfer as a confound to interpreting inner retinal neuronal transplantation following internal limiting membrane disruption. Stem Cell Reports , 18 (11) pp. 2203-2221. 10.1016/j.stemcr.2023.09.005. Green open access

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Abstract

Summary: Intercellular cytoplasmic material transfer (MT) occurs between transplanted and developing photoreceptors and ambiguates cell origin identification in developmental, transdifferentiation, and transplantation experiments. Whether MT is a photoreceptor-specific phenomenon is unclear. Retinal ganglion cell (RGC) replacement, through transdifferentiation or transplantation, holds potential for restoring vision in optic neuropathies. During careful assessment for MT following human stem cell-derived RGC transplantation into mice, we identified RGC xenografts occasionally giving rise to labeling of donor-derived cytoplasmic, nuclear, and mitochondrial proteins within recipient Müller glia. Critically, nuclear organization is distinct between human and murine retinal neurons, which enables unequivocal discrimination of donor from host cells. MT was greatly facilitated by internal limiting membrane disruption, which also augments retinal engraftment following transplantation. Our findings demonstrate that retinal MT is not unique to photoreceptors and challenge the isolated use of species-specific immunofluorescent markers for xenotransplant identification. Assessment for MT is critical when analyzing neuronal replacement interventions.

Type: Article
Title: Rare intercellular material transfer as a confound to interpreting inner retinal neuronal transplantation following internal limiting membrane disruption
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.stemcr.2023.09.005
Publisher version: http://dx.doi.org/10.1016/j.stemcr.2023.09.005
Language: English
Additional information: This is an Open Access publication made available via a Creative Commons Licence. See: http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Regeneration, transplantation, retina, neuron, central nervous system, CNS, cell lineage, cell tracking, material transfer, cytoplasmic exchange
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10193269
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