Transplanted human cones incorporate into the retina and function in a murine cone degeneration model
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
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.
Details
| Originalsprache | Englisch |
|---|---|
| Aufsatznummer | e154619 |
| Seitenumfang | 19 |
| Fachzeitschrift | The Journal of clinical investigation |
| Jahrgang | 132 |
| Ausgabenummer | 12 |
| Frühes Online-Datum | 28 Apr. 2022 |
| Publikationsstatus | Veröffentlicht - 28 Apr. 2022 |
| Peer-Review-Status | Ja |
Externe IDs
| Mendeley | a08e43f6-39f9-3b32-96a2-6c69195ccbb4 |
|---|---|
| Scopus | 85130349453 |
| WOS | 000814089100002 |
| unpaywall | 10.1172/jci154619 |
| ORCID | /0000-0001-5624-1717/work/142239046 |
| ORCID | /0000-0002-0926-6556/work/142250478 |
| ORCID | /0000-0001-9467-7677/work/161888179 |
Schlagworte
Forschungsprofillinien der TU Dresden
- Onkologie - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Biophysik und Bioengineering - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Regenerative Therapien - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Neurowissenschaften - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Gesundheitswissenschaften, Biomedizin und Bioengineering - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
DFG-Fachsystematik nach Fachkollegium
- Molekulare Biologie und Physiologie von Nerven- und Gliazellen - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Entwicklungsneurobiologie - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Entwicklungsbiologie - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Allgemeine Genetik und funktionelle Genomforschung - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Molekulare und zelluläre Neurologie und Neuropathologie - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Immunologie - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Zellbiologie - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
Fächergruppen, Lehr- und Forschungsbereiche, Fachgebiete nach Destatis
- Biologie allgemein - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
- Zoologie - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
Ziele für nachhaltige Entwicklung
- SDG 3 – Gute Gesundheit und Wohlergehen - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
ASJC Scopus Sachgebiete
- Allgemeine Medizin - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
Schlagwörter
- Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism
Bibliotheksschlagworte
- 610 Medizin und Gesundheit - Animals, Ependymoglial Cells, Humans, Induced Pluripotent Stem Cells/transplantation, Mice, Photoreceptor Cells, Vertebrate/metabolism, Retina/metabolism, Retinal Cone Photoreceptor Cells, Retinal Degeneration/metabolism