Gavin Herbert Eye Institute, Ophthalmology Research, University of California-Irvine, Irvine, CA 92697-4390, USA.
Stem Cells Int. 2012;2012:939801. doi: 10.1155/2012/939801. Epub 2012 Apr 9.
Purpose. Transplantation of stem, progenitor, or precursor cells has resulted in photoreceptor replacement and evidence of functional efficacy in rodent models of retinal degeneration. Ongoing work has been directed toward the replication of these results in a large animal model, namely, the pig. Methods. Retinal progenitor cells were derived from the neural retina of GFP-transgenic pigs and transplanted to the subretinal space of rhodopsin Pro347Leu-transgenic allorecipients, in the early stage of the degeneration and the absence of immune suppression. Results. Results confirm the survival of allogeneic porcine RPCs without immune suppression in the setting of photoreceptor dystrophy. The expression of multiple photoreceptor markers by grafted cells included the rod outer segment-specific marker ROM-1. Further evidence of photoreceptor differentiation included the presence of numerous photoreceptor rosettes within GFP-positive grafts, indicative of the development of cellular polarity and self-assembly into rudiments of outer retinal tissue. Conclusion. Together, these data support the tolerance of RPCs as allografts and demonstrate the high level of rod photoreceptor development that can be obtained from cultured RPCs following transplantation. Strategies for further progress in this area, together with possible functional implications, are discussed.
目的。干细胞、祖细胞或前体细胞的移植已经导致了光感受器的替代，并在视网膜变性的啮齿动物模型中证明了其功能效果。目前的工作重点是在大型动物模型（即猪）中复制这些结果。方法。从 GFP 转基因猪的神经视网膜中分离出视网膜祖细胞，并将其移植到视紫红质 Pro347Leu 转基因同种异体受者的视网膜下腔，在变性的早期阶段且没有免疫抑制。结果。结果证实，在感光器营养不良的情况下，在没有免疫抑制的情况下，同种异体猪 RPC 可以存活。移植细胞表达多种光感受器标记物，包括杆状外节特异性标记物 ROM-1。进一步证明光感受器分化的证据包括在 GFP 阳性移植物内存在大量光感受器玫瑰花结，表明细胞极性的发展和自我组装成外视网膜组织的雏形。结论。这些数据共同支持 RPC 作为同种异体移植物的耐受性，并证明了从培养的 RPC 移植后可以获得高水平的杆状光感受器发育。讨论了在这一领域进一步发展的策略以及可能的功能意义。
