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

Kevin Y Zhang; Arumugam Nagalingam; Stella Mary; Erika A Aguzzi; Weifeng Li; Nitin Chetla; Barbara Smith; Michael E Paulaitis; Malia M Edwards; Harry A Quigley; Donald J Zack; Thomas V Johnson

doi:10.1016/j.stemcr.2023.09.005

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

Stem Cell Reports. 2023 Nov 14;18(11):2203-2221. doi: 10.1016/j.stemcr.2023.09.005. Epub 2023 Oct 5.

Authors

Affiliations

¹ Glaucoma Center for Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
² Glaucoma Center for Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Glaucoma Center for Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Departments of Neuroscience, Molecular Biology and Genetics, and Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Glaucoma Center for Excellence, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Cellular and Molecular Medicine Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: johnson@jhmi.edu.

Abstract

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.

Keywords: CNS; cell lineage; cell tracking; central nervous system; cytoplasmic exchange; material transfer; neuron; regeneration; retina; transplantation.

MeSH terms

Animals
Humans
Mice
Neuroglia / metabolism
Photoreceptor Cells
Retina* / metabolism
Retinal Ganglion Cells
Retinal Neurons*

Abstract

MeSH terms

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