TY  - JOUR
AU  - Gasparini, Sylvia J
AU  - Tessmer, Karen
AU  - Reh, Miriam
AU  - Wieneke, Stephanie
AU  - Carido, Madalena
AU  - Völkner, Manuela
AU  - Borsch, Oliver
AU  - Swiersy, Anka
AU  - Zuzic, Marta
AU  - Goureau, Olivier
AU  - Kurth, Thomas
AU  - Busskamp, Volker
AU  - Zeck, Günther
AU  - Karl, Mike Oliver
AU  - Ader, Marius
TI  - Transplanted human cones incorporate and function in a murine cone degeneration model.
JO  - The journal of clinical investigation
VL  - 132
IS  - 12
SN  - 0021-9738
CY  - Ann Arbor, Mich.
PB  - ASCJ
M1  - DZNE-2022-00769
SP  - e154619
PY  - 2022
N1  - CC BY
AB  - 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.
KW  - Animals
KW  - Ependymoglial Cells
KW  - Humans
KW  - Induced Pluripotent Stem Cells: transplantation
KW  - Mice
KW  - Photoreceptor Cells, Vertebrate: metabolism
KW  - Retina: metabolism
KW  - Retinal Cone Photoreceptor Cells
KW  - Retinal Degeneration: metabolism
KW  - Retinal Degeneration: therapy
KW  - Human stem cells (Other)
KW  - Retinopathy (Other)
KW  - Stem cell transplantation (Other)
KW  - Stem cells (Other)
KW  - Transplantation (Other)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9197520
C6  - pmid:35482419
DO  - DOI:10.1172/JCI154619
UR  - https://pub.dzne.de/record/164106
ER  -