Sakaguchi D S, Van Hoffelen S J, Grozdanic S D, Kwon Y H, Kardon R H, Young M J
Department of Genetics, Development and Cell Biology, 503 Science II, Iowa State University, Ames, IA 50011, USA.
Ann N Y Acad Sci. 2005 May;1049:118-34. doi: 10.1196/annals.1334.012.
When developing cell transplant strategies to repair the diseased or injured central nervous system (CNS), it is essential to consider host-graft interactions and how they may influence the outcome of the transplants. Recent studies have demonstrated that transplanted neural progenitor cells (NPCs) can differentiate and integrate morphologically into developing mammalian retinas. Is the ability to differentiate and to undergo structural integration into the CNS unique to specific progenitor cells, or is this plasticity a function of host environment, or both? To address these issues we have used the developing retina of the Brazilian opossum and have compared the structural integration of brain and retinal progenitor cells transplanted into the eyes at different developmental stages. The Brazilian opossum, Monodelphis domestica, is a small pouchless marsupial native to South America. This animal's lack of a pouch and fetal-like nature at birth circumvents the need for in utero surgical procedures, and thus provides an ideal environment in which to study the interactions between developing host tissues and transplanted NPCs. To test whether NPCs affect visual function we transplanted adult hippocampal progenitor cells (AHPCs) into normal, healthy adult rat eyes and performed noninvasive functional recordings. Monitoring of the retina and optic nerve over time by electroretinography and pupillometry revealed no severe perturbation in visual function in the transplant recipient eyes. Taken together, our findings suggest that the age of the host environment can strongly influence NPC differentiation and that transplantation of neural progenitor cells may be a useful strategy aimed at treating neurodegeneration and pathology of the CNS.
在制定细胞移植策略以修复患病或受损的中枢神经系统（CNS）时，必须考虑宿主与移植物之间的相互作用以及它们如何影响移植结果。最近的研究表明，移植的神经祖细胞（NPC）可以分化并在形态上整合到发育中的哺乳动物视网膜中。这种分化并在结构上整合到中枢神经系统的能力是特定祖细胞所特有的，还是这种可塑性是宿主环境的作用，或者两者兼而有之？为了解决这些问题，我们利用了巴西负鼠发育中的视网膜，并比较了在不同发育阶段移植到眼中的脑祖细胞和视网膜祖细胞的结构整合情况。巴西负鼠（Monodelphis domestica）是一种原产于南美洲的无袋小有袋动物。这种动物出生时没有育儿袋且具有类似胎儿的特性，避免了子宫内手术的需要，因此提供了一个理想的环境来研究发育中的宿主组织与移植的神经祖细胞之间的相互作用。为了测试神经祖细胞是否影响视觉功能，我们将成年海马祖细胞（AHPC）移植到正常、健康的成年大鼠眼中，并进行了非侵入性功能记录。通过视网膜电图和瞳孔测量法对视网膜和视神经进行长期监测，结果显示移植受体眼中的视觉功能没有受到严重干扰。综上所述，我们的研究结果表明，宿主环境的年龄可以强烈影响神经祖细胞的分化，并且神经祖细胞移植可能是一种治疗中枢神经系统神经退行性变和病理状况的有用策略。
