Transplanted human cones incorporate and function in a murine cone degeneration model
| Autor: | Gasparini, Sylvia J, Tessmer, Karen, Kurth, Thomas, Busskamp, Volker, Zeck, Günther, Karl, Mike Oliver, Ader, Marius, Reh, Miriam, Wieneke, Stephanie, Carido, Madalena, Völkner, Manuela, Borsch, Oliver, Swiersy, Anka, Zuzic, Marta, Goureau, Olivier |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Transplantation
transplantation [Induced Pluripotent Stem Cells] metabolism [Retinal Degeneration] Ependymoglial Cells Stem cell transplantation Human stem cells Stem cells Mice therapy [Retinal Degeneration] Retinal Cone Photoreceptor Cells Animals Humans ddc:610 metabolism [Photoreceptor Cells Vertebrate] Retinopathy metabolism [Retina] |
| Zdroj: | The journal of clinical investigation 132(12), e154619 (2022). doi:10.1172/JCI154619 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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