A Reinterpretation of Cell Transplantation: GFP Transfer From Donor to Host Photoreceptors

作者：Arturo Ortín-Martínez, En Leh Samuel Tsai, Philip E. B. Nickerson, Miriam Bergeret, Yao Lu, Sheila Smiley, Lacrimioara Comanita, Valerie A. Wallace · 发表于：Stem Cells · 年份：2016 · DOI：10.1002/stem.2552 · 被引用次数：151 · 研究领域：Retinal Development and Disorders、Photoreceptor and optogenetics research、Neuroscience and Neural Engineering

Abstract The utilization of fluorescent reporter transgenes to discriminate donor versus host cells has been a mainstay of photoreceptor transplantation research, the assumption being that the presence of reporter+ cells in outer nuclear layer (ONL) of transplant recipients represents the integration of donor photoreceptors. We previously reported that GFP+ cells in the ONL of cone-GFP transplanted retinas exhibited rod-like characteristics, raising the possibility that GFP signal in recipient tissue may not be a consequence of donor cell integration. To investigate the basis for this mismatch, we performed a series of transplantations using multiple transgenic donor and recipient models, and assessed cell identity using nuclear architecture, immunocytochemistry, and DNA prelabeling. Our results indicate that GFP+ cells in the ONL fail to exhibit hallmark elements of donor cells, including nuclear hetero/euchromatin architecture. Furthermore, GFP signal does not appear to be a consequence of classic donor/host cell fusion or transfating post-transplant, but is most likely due to material exchange between donor and host photoreceptors. This transfer can be mediated by rods and cones, is bidirectional between donor and host cells, requires viable photoreceptors, occurs preferentially at sites of outer limiting membrane disruption and can be detected in second-order retinal neurons and Müller glia. Collectively, these data warrant re-evaluation of the use of lineage tracing fluo...