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@ARTICLE{Gasparini:164106,
      author       = {Gasparini, Sylvia J and Tessmer, Karen and Reh, Miriam and
                      Wieneke, Stephanie and Carido, Madalena and Völkner,
                      Manuela and Borsch, Oliver and Swiersy, Anka and Zuzic,
                      Marta and Goureau, Olivier and Kurth, Thomas and Busskamp,
                      Volker and Zeck, Günther and Karl, Mike Oliver and Ader,
                      Marius},
      title        = {{T}ransplanted human cones incorporate and function in a
                      murine cone degeneration model.},
      journal      = {The journal of clinical investigation},
      volume       = {132},
      number       = {12},
      issn         = {0021-9738},
      address      = {Ann Arbor, Mich.},
      publisher    = {ASCJ},
      reportid     = {DZNE-2022-00769},
      pages        = {e154619},
      year         = {2022},
      note         = {CC BY},
      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.},
      keywords     = {Animals / Ependymoglial Cells / Humans / Induced
                      Pluripotent Stem Cells: transplantation / Mice /
                      Photoreceptor Cells, Vertebrate: metabolism / Retina:
                      metabolism / Retinal Cone Photoreceptor Cells / Retinal
                      Degeneration: metabolism / Retinal Degeneration: therapy /
                      Human stem cells (Other) / Retinopathy (Other) / Stem cell
                      transplantation (Other) / Stem cells (Other) /
                      Transplantation (Other)},
      cin          = {Cell Culture Platform / AG Karl},
      ddc          = {610},
      cid          = {I:(DE-2719)1740003 / I:(DE-2719)1710004},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9197520},
      pubmed       = {pmid:35482419},
      doi          = {10.1172/JCI154619},
      url          = {https://pub.dzne.de/record/164106},
}