Stem cell therapy restores transparency to defective murine corneas.
Stem cell therapy restores transparency to defective murine corneas.
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DOI：
10.1002/stem.91
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发表时间：
2009-07
期刊：
影响因子：
5.2
通讯作者：
Funderburgh, James L.
中科院分区：
文献类型：
--
作者：
Du, Yiqin;Carlson, Eric C.;Funderburgh, Martha L.;Birk, David E.;Pearlman, Eric;Guo, Naxin;Kao, Winston W. -Y.;Funderburgh, James L.
关键词：
创伤和炎症造成的角膜疤痕扰乱了全球数百万人的视力，但作为治疗角膜失明的主要疗法，许多受影响的人无法获得角膜移植。在这项研究中，通过将干细胞直接注射到角膜基质中，检测了从成人角膜基质中分离的干细胞在小鼠模型中矫正基质混浊的能力。在野生型小鼠中，注射的人类干细胞在没有与宿主细胞融合或引发免疫T细胞反应的情况下仍然存活了几个月。人角膜特异性细胞外基质，包括蛋白多聚糖、鲁米肯和角化多糖，在处理后的角膜中积累。Lumcan基因缺失的小鼠由于基质胶原组织的破坏，导致角膜混浊，类似于疤痕组织。在注射人基质干细胞后，这些小鼠的基质厚度和胶原纤维缺陷恢复到正常小鼠的水平。接受治疗的小鼠的角膜透明度与野生型小鼠没有什么区别。这些结果支持成人干细胞的免疫豁免和干细胞治疗再生组织的能力，其方式类似于器官发生，明显不同于正常伤口愈合。结果表明，细胞疗法是治疗人类角膜失明的一种有效方法。
Corneal scarring from trauma and inflammation disrupts vision for millions worldwide, but corneal transplantation, the primary therapy for corneal blindness, is unavailable to many affected individuals. In this study, stem cells isolated from adult human corneal stroma were examined for the ability to correct stromal opacity in a murine model by direct injection of cells into the corneal stroma. In wild-type mice, injected human stem cells remained viable for months without fusing with host cells or eliciting an immune T-cell response. Human corneal-specific extracellular matrix, including the proteoglycans lumican and keratocan, accumulated in the treated corneas. Lumican-null mice have corneal opacity similar to that of scar tissue as a result of disruption of stromal collagen organization. After injection with human stromal stem cells, stromal thickness and collagen fibril defects in these mice were restored to that of normal mice. Corneal transparency in the treated mice was indistinguishable from that of wild-type mice. These results support the immune privilege of adult stem cells and the ability of stem cell therapy to regenerate tissue in a manner analogous to organogenesis and clearly different from that of normal wound healing. The results suggest that cell-based therapy can be an effective approach to treatment of human corneal blindness.
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