Extensive incorporation, polarisation and improved maturation of transplanted human cones in a murine cone degeneration model

Publikation: Vorabdruck/Dokumentation/BerichtVorabdruck (Preprint)

Beitragende

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 extend throughout the graft, even forming a common outer limiting membrane. Donor-host interaction appears 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 RPE. Putative synapse formation and graft function is 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

OriginalspracheEnglisch
PublikationsstatusVeröffentlicht - Aug. 2021
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Externe IDs

ORCID /0000-0001-5624-1717/work/151435761
ORCID /0000-0001-9467-7677/work/161888205
Mendeley 03650216-21e3-3093-8c40-f7642c5ca62d
unpaywall 10.1101/2021.08.26.457641

Schlagworte

Schlagwörter

  • Cone reporter, IPSC, Incorporation, Outer segment, Photoreceptor replacement, Polarisation, Retinal organoid, Transplantation