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000164106 1001_ $$aGasparini, Sylvia J$$b0
000164106 245__ $$aTransplanted human cones incorporate and function in a murine cone degeneration model.
000164106 260__ $$aAnn Arbor, Mich.$$bASCJ$$c2022
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000164106 520__ $$aOnce human photoreceptors die, they do not regenerate, thus photoreceptor transplantation has emerged as a potential treatment approach for blinding diseases. Improvements in transplant organization, donor cell maturation and synaptic connectivity to the host will be critical in advancing this technology to clinical practice. Unlike the unstructured grafts of prior cell suspension transplantations into end-stage degeneration models, we describe extensive incorporation of iPSC retinal organoid-derived human photoreceptors into mice with cone dysfunction. This incorporative phenotype was validated in both cone-only as well as pan-photoreceptor transplantations. Rather than forming a glial barrier, Müller cells extended throughout the graft, even forming a series of adherens junctions between mouse and human cells, reminiscent of an outer limiting membrane. Donor-host interaction appeared to promote polarisation as well as development of morphological features critical for light detection, namely formation of inner and well stacked outer segments oriented towards the retinal pigment epithelium. Putative synapse formation and graft function was evident both at a structural and electrophysiological level. Overall, these results show that human photoreceptors interact readily with a partially degenerated retina. Moreover, incorporation into the host retina appears to be beneficial to graft maturation, polarisation and function.
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000164106 650_7 $$2Other$$aHuman stem cells
000164106 650_7 $$2Other$$aRetinopathy
000164106 650_7 $$2Other$$aStem cell transplantation
000164106 650_7 $$2Other$$aStem cells
000164106 650_7 $$2Other$$aTransplantation
000164106 650_2 $$2MeSH$$aAnimals
000164106 650_2 $$2MeSH$$aEpendymoglial Cells
000164106 650_2 $$2MeSH$$aHumans
000164106 650_2 $$2MeSH$$aInduced Pluripotent Stem Cells: transplantation
000164106 650_2 $$2MeSH$$aMice
000164106 650_2 $$2MeSH$$aPhotoreceptor Cells, Vertebrate: metabolism
000164106 650_2 $$2MeSH$$aRetina: metabolism
000164106 650_2 $$2MeSH$$aRetinal Cone Photoreceptor Cells
000164106 650_2 $$2MeSH$$aRetinal Degeneration: metabolism
000164106 650_2 $$2MeSH$$aRetinal Degeneration: therapy
000164106 7001_ $$aTessmer, Karen$$b1
000164106 7001_ $$aReh, Miriam$$b2
000164106 7001_ $$0P:(DE-2719)2812103$$aWieneke, Stephanie$$b3
000164106 7001_ $$aCarido, Madalena$$b4
000164106 7001_ $$0P:(DE-2719)2810390$$aVölkner, Manuela$$b5$$udzne
000164106 7001_ $$aBorsch, Oliver$$b6
000164106 7001_ $$aSwiersy, Anka$$b7
000164106 7001_ $$aZuzic, Marta$$b8
000164106 7001_ $$aGoureau, Olivier$$b9
000164106 7001_ $$aKurth, Thomas$$b10
000164106 7001_ $$aBusskamp, Volker$$b11
000164106 7001_ $$aZeck, Günther$$b12
000164106 7001_ $$0P:(DE-2719)2000041$$aKarl, Mike Oliver$$b13$$udzne
000164106 7001_ $$aAder, Marius$$b14
000164106 773__ $$0PERI:(DE-600)2018375-6$$a10.1172/JCI154619$$n12$$pe154619$$tThe journal of clinical investigation$$v132$$x0021-9738$$y2022
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