Journal Article

DZNE-2022-00769

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Transplanted human cones incorporate and function in a murine cone degeneration model.

Gasparini, S. J. ; Tessmer, K. ; Reh, M. ; Wieneke, S.DZNE* ; Carido, M. ; Völkner, M.DZNE* ; Borsch, O. ; Swiersy, A. ; Zuzic, M. ; Goureau, O. ; Kurth, T. ; Busskamp, V. ; Zeck, G. ; Karl, M. O.DZNE* ; Ader, M.

2022
ASCJ Ann Arbor, Mich.

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Please use a persistent id in citations: doi:10.1172/JCI154619

Abstract: Once human photoreceptors die, they do not regenerate, thus photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation and synaptic connectivity to the host will be critical in advancing this technology to clinical practice. Unlike the unstructured grafts of prior cell suspension transplantations into end-stage degeneration models, we describe extensive incorporation of iPSC retinal organoid-derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extended throughout the graft, even forming a series of adherens junctions between mouse and human cells, reminiscent of an outer limiting membrane. Donor-host interaction appeared to promote polarisation as well as development of morphological features critical for light detection, namely formation of inner and well stacked outer segments oriented towards the retinal pigment epithelium. Putative synapse formation and graft function was evident both at a structural and electrophysiological level. Overall, these results show that human photoreceptors interact readily with a partially degenerated retina. Moreover, incorporation into the host retina appears to be beneficial to graft maturation, polarisation and function.

Keyword(s): Animals (MeSH) ; Ependymoglial Cells (MeSH) ; Humans (MeSH) ; Induced Pluripotent Stem Cells: transplantation (MeSH) ; Mice (MeSH) ; Photoreceptor Cells, Vertebrate: metabolism (MeSH) ; Retina: metabolism (MeSH) ; Retinal Cone Photoreceptor Cells (MeSH) ; Retinal Degeneration: metabolism (MeSH) ; Retinal Degeneration: therapy (MeSH) ; Human stem cells ; Retinopathy ; Stem cell transplantation ; Stem cells ; Transplantation

Note: CC BY

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Contributing Institute(s):

1. Cell Culture Platform (Cell Culture Platform)
2. Retina Regeneration and Degeneration (AG Karl)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2022

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Database coverage:
; ; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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