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将小鼠脑祖细胞整合到发育中的哺乳动物视网膜中。

Incorporation of murine brain progenitor cells into the developing mammalian retina.

作者信息

Van Hoffelen Samantha J, Young Michael J, Shatos Marie A, Sakaguchi Donald S

机构信息

Department of Zoology and Genetics, 339 Science II, Iowa State University, Ames, IA 50011, USA.

出版信息

Invest Ophthalmol Vis Sci. 2003 Jan;44(1):426-34. doi: 10.1167/iovs.02-0269.

Abstract

PURPOSE

To investigate the influence of a developing host environment on the survival, differentiation, and morphologic integration of murine brain progenitor cells (mBPCs) transplanted into the mammalian retina.

METHODS

Enhanced green fluorescent protein (GFP)-expressing murine brain progenitor cells were transplanted into developing and mature Brazilian opossums (Monodelphis domestica). Animals were allowed to survive for up to 4 weeks after transplantation, at which time the eyes were prepared for immunohistochemical analysis.

RESULTS

Transplanted mBPCs survived and differentiated in vivo, and extensive morphologic integration was observed within the host retinas. GFP-expressing cells often displayed morphologies characteristic of retinal neurons. GFP somata were located in nuclear layers, and their processes ramified throughout the inner (IPL) and outer (OPL) plexiform layers. Furthermore, in some cases, GFP-expressing neurites were confined to specific sublamina within the IPL. The greatest morphologic integration and differentiation were observed after transplantation into the youngest-aged host eyes. Some transplanted mBPCs incorporated within the inner retina expressed the neuronal markers microtubule associated protein (MAP)-2 or calretinin. Transplanted cells coexpressed GFP and recoverin only in the ONL.

CONCLUSIONS

mBPCs survived and morphologically integrated after xenotransplantation without immunosuppression. mBPCs were capable of incorporating into specific layers of the retina and expressing neuronal and retinal markers. The age of the host appeared to play a key role in determining cell fate in vivo.

摘要

目的

研究发育中的宿主环境对移植到哺乳动物视网膜中的小鼠脑祖细胞(mBPCs)存活、分化及形态整合的影响。

方法

将表达增强型绿色荧光蛋白(GFP)的小鼠脑祖细胞移植到发育中和成熟的巴西负鼠(Monodelphis domestica)体内。移植后让动物存活长达4周,此时将眼睛制备用于免疫组织化学分析。

结果

移植的mBPCs在体内存活并分化,在宿主视网膜内观察到广泛的形态整合。表达GFP的细胞常呈现视网膜神经元的特征形态。GFP胞体位于核层,其突起在内部(IPL)和外部(OPL)丛状层中分支。此外,在某些情况下,表达GFP的神经突局限于IPL内的特定亚层。移植到最年幼宿主眼中后观察到最大程度的形态整合和分化。一些在内视网膜中整合的移植mBPCs表达神经元标志物微管相关蛋白(MAP)-2或钙视网膜蛋白。移植细胞仅在ONL中共表达GFP和恢复蛋白。

结论

mBPCs在异种移植后无需免疫抑制即可存活并在形态上整合。mBPCs能够整合到视网膜的特定层中并表达神经元和视网膜标志物。宿主年龄似乎在决定体内细胞命运方面起关键作用。

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